Advanced Solid Tumors
Conditions
Keywords
Avelumab, M9241, NHS-IL12, Advanced Solid Tumors
Brief summary
The study consisted of 2 parts: Dose Escalation phase (Part A) and Expansion phase (Part B). The dose escalation phase evaluated the safety, tolerability, and PK of avelumab in combination with M9241 in subjects with locally advanced, unresectable, or metastatic solid tumors. Expansion phase assessed the safety and clinical activity of the combination regimen in selected tumor types. In Expansion phase subjects who had completed the combination treatment of avelumab at a given dose level of M9241, a safety review was performed by the Safety monitoring committee in order to make a decision on the next dose level. Successive cohorts of 3 to 6 subjects were treated with escalating doses of M9241 with avelumab intravenous (IV).
Interventions
DRUGAvelumab
Participants received avelumab intravenous (IV) infusion once a week on Day 1 and Day 15 of each cycle.
DRUGM9241
Participants received Subcutaneous (SC) injection of M9241 in escalating doses on Day 1 of each cycle.
DRUGAvelumab (Once weekly)
Participants received avelumab once weekly in combination with M9241 every 4 weeks at M9241 maximum tolerated dose (MTD) for first 12 weeks followed by avelumab once every 2 weeks plus M9241 once every 4 weeks at M9241 MTD until a criterion for treatment discontinuation has been met.
DRUGM9241 (MTD)
Participants received M9241 at M9241 MTD once every 4 weeks until a criterion for treatment discontinuation has been met.
DRUGAvelumab (Expansion cohort)
Participants in the expansion cohorts received Induction Therapy (Avelumab once weekly + M9241 once every 4 weeks) through Cycle 3 (for 12 weeks) then starting at Cycle 4, Continuation Therapy (Avelumab once every 2 weeks + M9241 once every 4 weeks).
Sponsors
Merck KGaA, Darmstadt, Germany
EMD Serono Research & Development Institute, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Part A: * subjects must had signed written informed consent. * male or female subjects age greater than equals to (\>=)18 years. * subjects must had histologically or cytologically proven metastatic or locally advanced solid tumors for which no standard therapy exists, standard therapy had failed, subject was intolerant of established therapy known to provided clinical benefit for their condition, or standard therapy was not acceptable to subject. * subjects who had been treated previously with a checkpoint inhibitor may enroll (except as outlined below for expansion cohorts). * at least 1 unidimensional radiographically measurable lesion based on response evaluation criteria in solid tumors (recist) version 1. 1 (v1. 1), except for subjects with metastatic castration-resistant prostate cancer (crpc) or metastatic breast cancer who may been enrolled with objective evidence of disease without a measureable lesion. - eastern cooperative oncology group (ecog) performance status of 0 to 1 at screening * estimated life expectancy of more than 12 weeks * adequate hematological function as defined below: * white blood cells (wbc) count \>= 3. 0 × 10\^9 per liter (/l) * absolute neutrophil count \>= 1. 5 × 10\^9/l * lymphocyte count \>= 0. 5 × 10\^9/l * platelet count \>= 100 × 10\^9/l * hemoglobin \>= 9 gram per deciliter (g/dl) (may had been transfused) * adequate hepatic function as defined below: * a total bilirubin level less than equals to (\<=) 1. 5 × upper limit of normal (uln) range * aspartate aminotransferase (ast) levels \<= 2. 5 × uln (≤ 3 × uln for expansion cohorts) * alanine aminotransferase (alt) levels \<= 2. 5 × uln (≤ 3 × uln for expansion cohorts) * subjects with documented gilbert disease were allowed if total bilirubin \> 1. 5 but less than 3 × uln * adequate renal function as defined by an estimated creatinine clearance \>= 50 milliliter per minute (ml/min) according to cockcroft-gault formula * negative blood pregnancy test at screening for women of childbearing potential. For purposes of this trial, women of childbearing potential were defined as all female subjects after puberty unless they were postmenopausal for at least 1 year, surgically sterile or sexually inactive. * highly effective contraception (ie, methods with a failure rate of less than 1% per year) must been used before started of treatment, for duration of trial treatment, and for at least 50 days after stopping studied treatment for both men and women if risk of conception exists. The effects of avelumab and m9241 on developing human fetus were unknown; thus, women of childbearing potential and men agreed to use highly effective contraception. Part B: * Availability of a fresh tumor biopsy was mandatory for eligibility in the RCC cohort. The biopsy or surgical specimen should be collected within 28 days prior to the first IMP administration. If a subject had 2 separate biopsy attempts in which usable tissue was not obtained, enrollment would have been possible after discussion with the Medical Monitor. For other expansion cohorts, availability of either tumor archival material (\< 6 months old) or fresh biopsies (obtained within 28 days) was acceptable with one of these being mandatory. For formalin-fixed paraffin-embedded samples, either block or sections (\> 15) provided. Tumor biopsies and tumor archival material should have been suitable for biomarker assessment - Locally advanced or metastatic UC that had progressed during or after at least one previous platinum-based chemotherapy and not previously treated with anti-PD-1/PD-L1 agents: Histologically or cytologically confirmed locally advanced or metastatic transitional cell carcinoma of urothelium(including renal pelvis, ureters, urinary bladder, and urethra). Participants must had progressed during or after treatment with at least 1 platinum-containing regimen for inoperable locally advanced or metastatic UC or disease recurrence. Participants who had received prior adjuvant/neoadjuvant chemotherapy and progressed within 12 months of treatment with a platinum-containing regimen were considered as second line. Participants with mixed histologies were required to have a dominant transitional cell pattern. * Non-small cell lung cancer (NSCLC), first-line metastatic: Stage IV (per seventh International Association for the Study of Lung Cancer classification) histologically confirmed NSCLC. Participants must not had received treatment for their metastatic disease. Participants could have received adjuvant chemotherapy or loco-regional treatment that included chemotherapy for locally advanced disease, as long as disease recurrence occurred at least 6 months after the completion of the last administration of chemotherapy. Only epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) wild-type were allowed (ie, EGFR mutation and ALK translocation / re arrangement excluded). Non squamous cell histologies and never / former light smoker (\< 15 pack years) squamous cell carcinoma Participants (per local standard of care) required testing if status was unknown. Participants must had low tumor PD-L1 expression defined as \< 50% tumor proportion score determined using PD-L1 IHC 22C3 pharmDx test or an equivalent Food and Drug Administration (FDA)- approved PD-L1 test. Availability of either tumor archival material or fresh biopsies within 28 days was acceptable with one of these being mandatory. For FFPE samples, either block or sections (\> 15) may be provided. Tumor biopsies and tumor archival material had been suitable for biomarker assessment. This cohort would not be opened for enrollment in Belgium, Czech Republic, France, Germany, Hungary, Italy, Netherlands, Spain, and United Kingdom. * Colorectal cancer (CRC): Histologically or cytologically confirmed recurrent or refractory metastatic CRC (according to American Joint Committee on Cancer / International Union Against Cancer Tumor Node Metastasis \[TNM\] Staging System seventh edition) after failure of prior therapy containing oxaliplatin / fluoropyrimidine and / or irinotecan / fluoropyrimidine and, if eligible, cetuximab (Erbitux®) and bevacizumab (Avastin®). Only Participants with microsatellite instability (MSI)-low or microsatellite stable (MSS) metastatic CRC are eligible. Participants without existing MSI test results had MSI status performed locally by a Clinical Laboratory Improvement Amendments (CLIA)-certified IHC or polymerase chain reaction (PCR)-based test (PCR based MSI test is preferred). Participants had to be willing to undergo an on-treatment biopsy procedure. Availability of either tumor archival material or fresh biopsies within 28 days was acceptable with one of these being mandatory. For FFPE samples, either a block or sections (\> 15) could be provided. Tumor biopsies and tumor archival material had to be suitable for biomarker assessment. For Belgium, Czech Republic, France, Germany, Hungary, Italy, Netherlands, Spain, and United Kingdom, participants in the second-line setting had exhausted or were considered ineligible or intolerant (in the opinion of the Investigator) of available second-line chemotherapy options. * Renal cell carcinoma (RCC), primary immune checkpoint inhibitor failure: Histologically or cytologically documented metastatic RCC with a component of clear cell subtype. Participants must have had progressive disease (PD) within 6 months or best overall response of stable disease (SD) for ≥ 6 months following start of therapy with any antibody / drug targeting T cell co-regulatory proteins (immune checkpoints) such as anti-PD-1, anti-PD-L1, or anticytotoxic T lymphocyte antigen-4 (CTLA-4) for advanced or metastatic disease (either as monotherapy or combination therapy, in any line). Fresh tumor biopsy was required for enrollment. If a subject had 2 separate biopsy attempts in which usable tissue was not obtained, enrollment could be possible after discussion with the Medical Monitor. Participants had to be willing to undergo an on-treatment biopsy procedure. In France, in addition to having received checkpoint inhibitor therapy, participants should have already received recommended local-standard therapy per discretion of the Investigator.
Exclusion criteria
* Concurrent treatment with a non-permitted drug/intervention (listed below) * Anticancer treatment (eg, cytoreductive therapy, radiotherapy, immune therapy, cytokine therapy, monoclonal antibody, targeted small molecule therapy) or any investigational drug within 4 weeks or 5 half-lives, whichever was shorter, prior to start of trial treatment, or not recovered from adverse event (AE) related to such therapies, with the following exceptions: Palliative radiotherapy delivered in a normal organ-sparing technique is permitted; Erythropoietin, darbepoetin-α and granulocyte colony-stimulating factor permitted; Hormonal therapies acting on the hypothalamic-pituitary-gonadal axis permitted (i.e. luteinizing hormone-releasing hormone agonist/antagonists). No other hormonal anticancer therapy was permitted. * Major surgery (as deemed by Investigator) for any reason, except diagnostic biopsy, within 4 weeks prior to start of trial treatment, or not fully recovered from surgery within 4 weeks prior to start of trial treatment. * Participants receiving immunosuppressive agents (such as steroids) for any reason were tapered off these drugs before start of trial treatment, with following exceptions: Participants with adrenal insufficiency, continued corticosteroids at physiologic replacement dose, equivalent to ≤ 10 mg prednisone daily; Administration of steroids through a route known to result in a minimal systemic exposure (topical, intranasal, intra-ocular, or inhalation) was permitted; Previous or ongoing administration of systemic steroids for the management of an acute allergic phenomenon was acceptable as long as it was anticipated that the administration of steroids would be completed in 14 days, or that the dose after 14 days would be equivalent to \<= 10 mg prednisone daily. * Any prior treatment with any form of interlukin-12 (IL-12) * For the NSCLC, CRC, and UC expansion cohorts, prior therapy with any antibody / drug targeting T-cell co-regulatory proteins (immune checkpoints) such as anti-PD-1, anti-PD-L1, or anticytotoxic T lymphocyte antigen-4 (CTLA-4) antibody was prohibited. * Intolerance to checkpoint inhibitor therapy, as defined by the occurrence of an AE requiring drug discontinuation. - Active or history of primary or metastatic central nervous system tumors * Prior organ transplantation, including allogeneic stem-cell transplantation * Previous malignant disease (other than the indication for this trial) within the last 5 years (except adequately treated non-melanoma skin cancers, carcinoma in situ of skin, bladder, cervix, colon/rectum, breast, or prostate) unless a complete remission without further recurrence was achieved at least 2 years prior to trial entry and subject was deemed to have been cured with no additional therapy required or anticipated to be required. * Significant acute or chronic infections requiring systemic therapy including, among others: • History of testing positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome • Hepatitis B or C infection (HBV surface antigen positive and HBV core antibody positive with reflex to positive HBV deoxy ribonucleic acid (DNA) or HBV core antibody positive alone with reflex to positive HBV DNA or positive hepatitis C virus \[HCV\] antibody with reflex to positive HCV ribonucleic acid \[RNA\]). Participants with history of infection must had polymerase chain reaction documentation that infection was cleared. * Active or history of autoimmune disease that might deteriorate when receiving an immuno-stimulatory agent. Participants with diabetes type I, vitiligo, psoriasis, hypo- or hyperthyroid disease not requiring immunosuppressive treatment wer eligible if they wer stable on other medical treatment and do not fulfill exclusion criterion including Uncontrolled intercurrent illness - Known severe hypersensitivity reactions to monoclonal antibodies (Grade\>= 3 National Cancer Institute-Common Terminology Criteria for Adverse Event (NCI-CTCAE) v4.03, or uncontrolled asthma (ie, 3 or more features of partially controlled asthma) * History of allergic reaction to methotrexate (trace methotrexate may be present in M9241 as a part of manufacturing process) or history of severe hypersensitivity reaction to any other ingredient of study drug(s) and / or their excipients. Since M9241 contains sucrose as an excipient, participants suffering from hereditary fructose intolerance also excluded - Persisting toxicity related to prior therapy of Grade \> 1 NCI-CTCAE v4.03 with the following exceptions: * Neuropathy Grade \<= 2 was acceptable. * All grades of alopecia acceptable. * Endocrine dysfunction on replacement therapy was acceptable. * Pregnancy or lactation * Known alcohol or drug abuse as deemed by the Investigator * Uncontrolled intercurrent illness including, but not limited to: * Hypertension uncontrolled by standard therapies (not stabilized to 150/90 millimeter of mercury (mm Hg) or lower) * Uncontrolled active infection * Uncontrolled diabetes (eg, glycosylated hemoglobin \[HgbA1c\] \>= 8%) * Clinically significant (or active) cardiovascular disease: cerebral vascular accident/stroke (\< 6 months prior to enrollment), myocardial infarction (\< 6 months prior to enrollment), unstable angina, congestive heart failure (New York Heart Association Classification Class \>= II), or serious cardiac arrhythmia requiring medication * All other significant diseases (eg, inflammatory bowel disease, current severe acute or chronic colitis) or chronic medical conditions (including laboratory abnormalities) that in opinion of Investigator might impair subject's tolerance of trial treatment or interpretation of trial results. * Any psychiatric condition that would prohibit understanding or endering of informed consent or that would limit compliance with trial requirements. * Legal incapacity or limited legal capacity. * Administration of a live vaccine within 30 days prior to trial entry. * Any subject with possible area of ongoing necrosis (non-disease related), such as active ulcer, non-healing wound, or intercurrent bone fracture that may be at risk of delayed healing due to protocol therapy. * Oxygen saturation \< 90% at rest, known pulmonary fibrosis, or active interstitial lung disease. * History of congenital or active immunodeficiency, with exception of acquired treatment-related hypogammaglobulinemia requiring periodic IV immunoglobulin infusion.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part A: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment-Related TEAEs According to National Cancer Institute-Common Terminology Criteria for Adverse Event (NCI-CTCAE) v4.03 | From first dose of study treatment up to 1311 days | An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a product or medical device; the event needed not necessarily have a causal relationship with the treatment or usage. Serious AE: an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. TEAE: AE with onset after start of treatment or with onset date before the treatment start date but worsening after the treatment start date. TEAEs included both serious and non-serious TEAEs. Treatment-related TEAEs: reasonably related to the study intervention. Number of participants with TEAEs and treatment related TEAEs were reported. |
| Part B: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment-Related TEAEs According to National Cancer Institute-Common Terminology Criteria for Adverse Event (NCI-CTCAE) v4.03 | Part B: From first dose of study treatment up to 443 days | An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a product or medical device; the event needed not necessarily have a causal relationship with the treatment or usage. Serious AE: an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. TEAE: AE with onset after start of treatment or with onset date before the treatment start date but worsening after the treatment start date. TEAEs included both serious and non-serious TEAEs. Treatment-related TEAEs: reasonably related to the study intervention. Number of participants with TEAEs and treatment related TEAEs were reported. |
| Part A: Number of Participants With Treatment-Related Adverse Events (TRAEs) by Severity Based on Grade 3,4 and 5 According to National Cancer Institute-Common Terminology Criteria for Adverse Events Version 4.03 (NCI-CTCAE v4.03) | From first dose of study treatment up to 1311 days | AE was any untoward medical occurrence in a participants who received study drug without regard to possibility of causal relationship. An AE was considered treatment emergent if occurred for the first time after the start of study treatment or occurred prior to the start of treatment. Severity of TEAEs were graded using NCI-CTCAE v4.03 toxicity grades, as follows: Grade 3 = Severe; Grade 4 = Life-threatening and Grade 5 = Death. Number of participants with Grade 3,4 and 5 by severity were only reported. |
| Part B: Number of Participants With Treatment-Related Adverse Events (TRAEs) by Severity According to National Cancer Institute-Common Terminology Criteria for Adverse Events Version 4.03 (NCI-CTCAE v4.03) | First dose of study drug up to 443 days | AE was any untoward medical occurrence in a participants who received study drug without regard to possibility of causal relationship. An AE was considered treatment emergent if occurred for the first time after the start of study treatment or occurred prior to the start of treatment. Severity of TEAEs were graded using NCI-CTCAE v4.03 toxicity grades, as follows: Grade 1= Mild; Grade 2 = Moderate; Grade 3 = Severe; Grade 4 = Life-threatening and Grade 5 = Death. Number of participants with TEAEs and TRAEs by severity were reported. |
| Part A: Number of Participants Experiencing Dose Limiting Toxicities (DLTs) | Time from first treatment to final assessment up to 3 weeks | A DLT is any Grade (\>=) 3 non-hematologic AE or any Grade (\>=) 4 hematologic AE according to the NCI-CTCAE v4.03, occurring during the DLT observation period that is related to either or both study drugs as determined by the Investigator or Sponsor at any dose and judged not to be related to the underlying disease or any previous or concomitant medication. The following are exceptions to the DLTs: Grade \>=3 thrombocytopenia with medically concerning bleeding; Any Grade 3 autoimmune thyroid-related toxicity that doesn't clinically resolve to \<= Grade 2 within 7 days of initiating therapy will be a DLT. Any Grade 4 neutropenia of \< 5 days duration; Grade 3 infusion-related reaction resolving within 6 hours of infusion; Grade 3 diarrhea or skin toxicity that resolves to Grade \<= 1 within 7 days after medical management; Transient Grade 3 fatigue, local reactions, flu-like symptoms; Tumor flare phenomenon of known or suspected tumor did not consider a DLT. |
| Part B: Number of Participants With Confirmed Best Overall Response (BOR) Assessed by Investigator Using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 | First dose of study drug up to 443 days | Confirmed BOR was defined as the best response of any of the confirmed complete response (CR), confirmed partial response (PR), stable disease (SD) and progressive disease (PD) recorded from the date of randomization until disease progression or recurrence (taking the smallest measurement recorded since the start of treatment as reference).CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30 percent (%) reduction from baseline in the sum of the longest diameter (SLD) of all lesions. Stable disease (SD)= Neither sufficient increase to qualify for progression of disease (PD) nor sufficient shrinkage to qualify for PR. PD: At least a 20 % increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions. Not evaluable (NE): No post-baseline assessment. BOR assessments were assessed by investigators. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part A: Apparent Terminal Half-life (t1/2) of Avelumab | PrD, 1, 4, 8 hours PD on Day 1, 22 of cycle 1 & 2; PrD, 1 hour PD on Day 8, 15 of cycle 1 & Day 8, 15, 22 of cycle 2; PrD, 1 hour PD on Day 1 cycle 3 & Day 1, 15 of cycle 4; PrD on Day 1 of cycle 7, 10,13,16,19,22,25, & 28 (Each cycle: 28 days) | Apparent terminal half-life was defined as the time required for the serum concentration of drug to decrease 50 percent in the final stage of its elimination. |
| Part A: Area Under the Serum Concentration-Time Curve Within One Dosing Interval (AUC0-tau) of Avelumab | PrD, 1, 4, 8 hours PD on Day 1, 22 of cycle 1 & 2; PrD, 1 hour PD on Day 8, 15 of cycle 1 & Day 8, 15, 22 of cycle 2; PrD, 1 hour PD on Day 1 cycle 3 & Day 1, 15 of cycle 4; PrD on Day 1 of cycle 7, 10,13,16,19,22,25, & 28 (Each cycle: 28 days) | AUCtau was defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval). |
| Part A: Area Under Serum Concentration Time Curve From Time Zero to the Time of the Last Observation (AUC0-t) of M9241 | PrD, 1, 4, 8 hours PD on Day 1 of cycle 1 and Day 1 of cycle 2; PrD on Day 15 of cycle 1 and cycle 2; PrD, 1hour PD on Day 1 of cycle 3 and cycle 4; PrD on Day 1 Cycle 7, 10, 13, 16, 19, 22, 25, and 28 (Each cycle: 28 days) | Area under the serum concentration versus time curve from time zero to the last sampling time t at which the concentration is at or above the lower limit of quantification (LLLQ). (AUC0-t) was calculated according to the mixed log-linear trapezoidal rule. |
| Part A: Area Under Serum Concentration Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of M9241 | PrD, 1, 4, 8 hours PD on Day 1 of cycle 1 and Day 1 of cycle 2; PrD on Day 15 of cycle 1 and cycle 2; PrD, 1hour PD on Day 1 of cycle 3 and cycle 4; PrD on Day 1 Cycle 7, 10, 13, 16, 19, 22, 25, and 28 (Each cycle: 28 days) | The AUC(0-inf) was estimated by determining the total area under the curve of the concentration versus time curve extrapolated to infinity. |
| Part A: Terminal Elimination Rate Constant (Lambdaz) of M9241 | PrD, 1, 4, 8 hours PD on Day 1 of cycle 1 and Day 1 of cycle 2; PrD on Day 15 of cycle 1 and cycle 2; PrD, 1 hour PD on Day 1 of cycle 3 and cycle 4; PrD on Day 1 Cycle 7, 10, 13, 16, 19, 22, 25, and 28 (Each cycle: 28 days) | Lambda(z) was determined from the terminal slope of the log-transformed serum concentration curve using linear regression method. |
| Part A: Maximum Observed Serum Concentration (Cmax) of M9241 | PrD, 1, 4, 8 hours PD on Day 1 of cycle 1 and Day 1 of cycle 2; PrD on Day 15 of cycle 1 and cycle 2; PrD, 1 hour PD on Day 1 of cycle 3 and cycle 4; PrD on Day 1 Cycle 7, 10, 13, 16, 19, 22, 25, and 28 (Each cycle: 28 days) | Cmax is the maximum observed serum concentration obtained directly from the concentration versus time curve. |
| Part A: Minimum Observed Serum Concentration (Cmin) of M9241 | PrD, 1, 4, 8 hours PD on Day 1 of cycle 1 and Day 1 of cycle 2; PrD on Day 15 of cycle 1 and cycle 2; PrD, 1 hour PD on Day 1 of cycle 3 and cycle 4; PrD on Day 1 Cycle 7, 10, 13, 16, 19, 22, 25, and 28 (Each cycle: 28 days) | Cmin is minimum observed serum concentration obtained directly from the concentration versus time curve. |
| Part A: Time to Reach Maximum Observed Concentration (Tmax) of M9241 | PrD, 1, 4, 8 hours PD on Day 1 of cycle 1 and Day 1 of cycle 2; PrD on Day 15 of cycle 1 and cycle 2; PrD, 1 hour PD on Day 1 of cycle 3 and cycle 4; PrD on Day 1 Cycle 7, 10, 13, 16, 19, 22, 25, and 28 (Each cycle: 28 days) | Tmax is time to reach maximum observed serum concentration obtained directly from the concentration versus time curve. |
| Part A: Apparent Terminal Half-life (t1/2) of M9241 | PrD, 1, 4, 8 hours PD on Day 1 of cycle 1 and Day 1 of cycle 2; PrD on Day 15 of cycle 1 and cycle 2; PrD, 1 hour PD on Day 1 of cycle 3 and cycle 4; PrD on Day 1 Cycle 7, 10, 13, 16, 19, 22, 25, and 28 (Each cycle: 28 days) | Apparent terminal half-life was defined as the time required for the serum concentration of drug to decrease 50 percent in the final stage of its elimination. |
| Part A: Area Under the Serum Concentration-Time Curve Within One Dosing Interval (AUC0-tau) of M9241 | PrD, 1, 4, 8 hours PD on Day 1 of cycle 1 and Day 1 of cycle 2; PrD on Day 15 of cycle 1 and cycle 2; PrD, 1 hour PD on Day 1 of cycle 3 and cycle 4; PrD on Day 1 Cycle 7, 10, 13, 16, 19, 22, 25, and 28 (Each cycle: 28 days) | AUCtau was defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval). |
| Part A: Area Under Serum Concentration Time Curve From Time Zero to the Time of the Last Observation (AUC0-t) of Avelumab | Predose (PrD),1,4,8 hours postdose (PD) on Day 1,22 of Cycle 1 & 2; PrD,1 hour PD on Day 8,15 of Cycle 1 & Day 8,15,22 of Cycle 2; PrD, 1 hour PD on Day 1 Cycle 3 & Day 1,15 of Cycle 4; PrD on Day 1 of Cycle 7,10,13,16,19,22,25, & 28 (Each cycle: 28 days) | Area under the serum concentration versus time curve from time zero to the last sampling time t at which concentration is at or above the lower limit of quantification (LLLQ). AUC0-t was calculated according to the mixed log-linear trapezoidal rule. |
| Part A: Number of Participants With Confirmed Best Overall Response (BOR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 | First dose of study drug up to 1311 days | BOR is defined as best response of any of confirmed complete response, confirmed partial response, stable disease and progressive disease recorded from date of randomization until disease progression or recurrence. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30 percent (%) reduction from baseline in the sum of the longest diameter (SLD) of all lesions. Stable disease (SD)= Neither sufficient increase to qualify for progression of disease (PD) nor sufficient shrinkage to qualify for PR. PD: At least a 20 % increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions. Non-CR/non-PD (for participants with non-measurable disease at baseline) = at least one Non-CR/non-PD assessment (or better) \>= 6 weeks after first study treatment administration and before progression and Not Evaluable: all other cases. BOR assessments were assessed by investigators. |
| Part B: Serum Trough Concentration Levels (Ctrough) of M9241 | Pre-dose, 1 hour post-dose on Day 1 of cycle 2; Day 1, 27 of cycle 3; Day 1 of cycle 5 (Each cycle: 28 days) | Ctrough was defined as the trough or minimum serum concentration. |
| Part B: Concentration at the End of Infusion (Ceoi) of Avelumab | Pre-dose, 1 hour post-dose on Day 1 and 15 of Cycle 1 and 2 (Each cycle: 28 days) | Ceoi is the observed serum drug concentration at the end of Intravenous (IV) infusion. |
| Pat A: Number of Participants With Immune-related Best Overall Response (BOR) Using Immune-related Response Criteria Derived From Response Evaluation Criteria in Solid Tumors Version 1.1 | First dose of study drug up to 1311 days | BOR: best response of any of immune related complete response (irCR), immune related partial response (irPR), immune related stable disease (irSD) and immune related progressive disease (irPD) recorded from the date of randomization until disease progression or recurrence (taking the smallest measurement recorded since the start of treatment as reference). irCR: Complete disappearance of all tumor lesions (both index and non-index lesions with no new measurable/unmeasurable lesions). irPR: At least 30% reduction from baseline in the sum of the longest diameter (SLD) of all lesions). irSD: SLD of target and new measurable lesions neither irCR, irPR, or irPD. irPD: SLD of target and new measurable lesions increases greater than or equal to \[\>=\] 20%, confirmed by a repeat, consecutive observations at least 4 weeks from the date first documented. Number of participants with immune-related best overall response in each category (irCR, irPR, irSD, irPD) was reported. |
| Part B: Serum Trough Concentration Levels (Ctrough) of Avelumab | Pre-dose, 1 hour post-dose on Day 15, 29 and 43 | Ctrough was defined as the trough or minimum serum concentration. |
| Part B: Progression Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) Criteria Assessed by Investigator | Time from first dose administration until progressive disease or death, assessed up to 443 days | PFS was defined as the time from first treatment day until date of the first documentation of progressive disease (PD) or death due to any cause, whichever occurs first. PD was defined as at least a 20 percent (%) increase in the sum of longest diameter (SLD), taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions. PFS was measured using Kaplan-Meier estimates. |
| Part B: Overall Survival (OS) Time | Time from first dose of study treatment up to 443 days | The OS time was defined as the time from treatment day 1 to the date of death due to any cause. The participants who were still alive at the time of data analysis or who were lost to follow-up OS time was censored at the last recorded date that the participant was known to be alive before the data cutoff date. OS was measured using Kaplan-Meier estimates. |
| Part B: Duration of Response (DOR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) Criteria Assessed by Investigator | Time from first dose of study treatment up to 443 days | DOR according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) and as assessed by an Investigator was defined as the time from first documentation of objective response (Complete Response \[CR\] or Partial Response \[PR\]) to the date of first documentation of objective progression of disease (PD) or death due to any cause whichever occurs first. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the sum of the longest diameter (SLD) of all lesions. PD was defined as at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions. If a participant has not an event (PD or death), DOR was censored at the date of last adequate tumor assessment. |
| Part B: Maximum Observed Serum Concentration (Cmax) of M9241 | Pre-dose, 1 hour post-dose on Day 1 and Day 29 of Cycle 1 and 2 (Each cycle: 28 days) | Cmax is the maximum observed serum concentration obtained directly from the concentration versus time curve. |
| Part B: Number of Participants With At Least One Positive Anti-drug Antibodies (ADA) of Avelumab and M9241 | Time from first dose of study treatment up to 443 days | ADA category of each participant was classified as pre-existing immunoreactivity (positive ADA response at baseline (prior to treatment), treatment-boosted (positive response at baseline with at least one post baseline titer at \>=8-fold baseline titer), or treatment-emergent (TE \[any positive post baseline assay response when baseline results were negative or missing or not reported\]). TE ADA responses were further classified as persistent (treatment-emergent positive ADA response detected in at least 2 consecutive post baseline samples separated by at least a 16-week post baseline period \[based on nominal sampling time\], with no ADA-negative samples in-between or positive response at last ADA sampling time point) and transient (not persistent/indeterminate, regardless of any missing samples). |
| Part A: Number of Participants With At Least One Positive Anti-drug Antibodies (ADA) for Avelumab and M9241 | First dose of study drug up to 1311 days | ADA category of each participant was classified as pre-existing immunoreactivity (positive ADA response at baseline (prior to treatment), treatment-boosted (positive response at baseline with at least one post baseline titer at \>=8-fold baseline titer), or treatment-emergent (TE \[any positive post baseline assay response when baseline results were negative or missing or not reported\]). TE ADA responses were further classified as persistent (treatment-emergent positive ADA response detected in at least 2 consecutive post baseline samples separated by at least a 16-week post baseline period \[based on nominal sampling time\], with no ADA-negative samples in-between or positive response at last ADA sampling time point) and transient (not persistent/indeterminate, regardless of any missing samples). |
| Part A: Area Under Serum Concentration Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Avelumab | PrD, 1, 4, 8 hours PD on Day 1, 22 of cycle 1 & 2; PrD, 1 hour PD on Day 8, 15 of cycle 1 & Day 8, 15, 22 of cycle 2; PrD, 1 hour PD on Day 1 cycle 3 & Day 1, 15 of cycle 4; PrD on Day 1 of cycle 7, 10,13,16,19,22,25, & 28 (Each cycle: 28 days) | The AUC(0-inf) was estimated by determining the total area under the curve of the concentration versus time curve extrapolated to infinity. |
| Part A: Terminal Elimination Rate Constant (Lambdaz) of Avelumab | PrD, 1, 4, 8 hours PD on Day 1, 22 of cycle 1 & 2; PrD, 1 hour PD on Day 8, 15 of cycle 1 & Day 8, 15, 22 of cycle 2; PrD, 1 hour PD on Day 1 cycle 3 & Day 1, 15 of cycle 4; PrD on Day 1 of cycle 7, 10,13,16,19,22,25, & 28 (Each cycle: 28 days) | Lambda(z) was determined from the terminal slope of the log-transformed serum concentration curve using linear regression method. |
| Part A: Maximum Observed Serum Concentration (Cmax) of Avelumab | PrD, 1, 4, 8 hours PD on Day 1, 22 of cycle 1 & 2; PrD, 1 hour PD on Day 8, 15 of cycle 1 & Day 8, 15, 22 of cycle 2; PrD, 1 hour PD on Day 1 cycle 3 & Day 1, 15 of cycle 4; PrD on Day 1 of cycle 7, 10,13,16,19,22,25, & 28 (Each cycle: 28 days) | Cmax is the maximum observed serum concentration obtained directly from the concentration versus time curve. |
| Part A: Minimum Observed Serum Concentration (Cmin) of Avelumab | PrD, 1, 4, 8 hours PD on Day 1, 22 of cycle 1 & 2; PrD, 1 hour PD on Day 8, 15 of cycle 1 & Day 8, 15, 22 of cycle 2; PrD, 1 hour PD on Day 1 cycle 3 & Day 1, 15 of cycle 4; PrD on Day 1 of cycle 7, 10,13,16,19,22,25, & 28 (Each cycle: 28 days) | Cmin is minimum observed serum concentration obtained directly from the concentration versus time curve. |
| Part A: Time to Reach Maximum Observed Concentration (Tmax) of Avelumab | PrD, 1, 4, 8 hours PD on Day 1, 22 of cycle 1 & 2; PrD, 1 hour PD on Day 8, 15 of cycle 1 & Day 8, 15, 22 of cycle 2; PrD, 1 hour PD on Day 1 cycle 3 & Day 1, 15 of cycle 4; PrD on Day 1 of cycle 7, 10,13,16,19,22,25, & 28 (Each cycle: 28 days) | Tmax is time to reach maximum observed serum concentration obtained directly from the concentration versus time curve. |
Countries
Belgium, France, Hungary, Italy, Netherlands, Spain, United States
Participant flow
Recruitment details
The study consisted of 2 parts: Part A (Dose escalation) and Part B (Dose expansion).
Pre-assignment details
The study was conducted at 33 sites within Europe and the United States.
Participants by arm
| Arm | Count |
|---|---|
| Part A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kg (Experimental) Participants received M9241 at a dose of 4 micrograms per kilogram (mcg/kg) a subcutaneous (SC) injection at time (up to -20 minutes) relative to the start of Avelumab infusion (time 0), once every 4 weeks, on Day 1 in combination with Avelumab 10 milligrams per kilogram (mg/kg) intravenous (IV) infusion every 2 weeks on Day 1 and 15 during each cycle (Each cycle=28 days) until any criterion for treatment discontinuation were met. | 9 |
| Part A Cohort 2: M9241 8 mcg/kg + Avelumab 10 mg/kg (Experimental) Participants received M9241 at a dose of 8 mcg/kg SC injection at time (up to -20 minutes) relative to the start of avelumab infusion (time 0), once every 4 weeks, on Day 1 in combination with Avelumab 10 mg/kg IV infusion every 2 weeks on Day 1 and 15 of each cycle (Each cycle=28 days) until any criterion for treatment discontinuation were met. | 7 |
| Part A Cohort 3: M9241 12 mcg/kg + Avelumab 10 mg/kg (Experimental) Participants received M9241 at a dose of 12 mcg/kg SC injection at time (up to -20 minutes) relative to the start of avelumab infusion (time 0), once every 4 weeks, on Day 1 in combination with Avelumab 10 mg/kg IV infusion every 2 weeks on Day 1 and 15 of each cycle (Each cycle=28 days) until any criterion for treatment discontinuation were met. | 7 |
| Part A Cohort 4: M9241 16.8 mcg/kg +Avelumab 10 mg/kg (Experimental) Participants received M9241 at a dose of 16.8 mcg/kg SC injection at time (up to -20 minutes) relative to the start of avelumab infusion (time 0), once every 4 weeks, on Day 1 in combination with Avelumab 10 mg/kg IV infusion every 2 weeks on Day 1 and 15 of each cycle (Each cycle=28 days) until any criterion for treatment discontinuation were met. | 6 |
| Part A Cohort 5: M9241 16.8 mcg/kg + Avelumab 800 mg (Experimental) Participants received M9241 at a dose of 16.8 mcg/kg SC injection at time (up to -20 minutes) relative to the start of avelumab infusion (time 0), once every 4 weeks, on Day 1 in combination with Avelumab 800 milligrams (mg) IV infusion once weekly for the first 12 weeks, then 800 mg once every 2 weeks of each cycle (Each cycle=28 days) until any criterion for treatment discontinuation were met. | 7 |
| Part B Cohort 1: UC Cohort Stage 1 Combination Therapy (Experimental) Participants in the expansion cohorts received M9241 at dose of 16.8 mcg/kg SC injection at time (up to -20 minutes) relative to the start of avelumab infusion (time 0), once every 4 weeks on Day 1 in combination with Avelumab 800 mg IV infusion once weekly for the first 12 weeks, then 800 mg once every 2 weeks of each cycle (Each cycle=28 days) determined as the RP2D in the escalation part of the study. | 16 |
| Total | 52 |
Baseline characteristics
| Characteristic | Part A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kg (Experimental) | Part A Cohort 2: M9241 8 mcg/kg + Avelumab 10 mg/kg (Experimental) | Part A Cohort 3: M9241 12 mcg/kg + Avelumab 10 mg/kg (Experimental) | Part A Cohort 4: M9241 16.8 mcg/kg +Avelumab 10 mg/kg (Experimental) | Part A Cohort 5: M9241 16.8 mcg/kg + Avelumab 800 mg (Experimental) | Part B Cohort 1: UC Cohort Stage 1 Combination Therapy (Experimental) | Total |
|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 3 Participants | 3 Participants | 3 Participants | 1 Participants | 2 Participants | 8 Participants | 20 Participants |
| Age, Categorical Between 18 and 65 years | 6 Participants | 4 Participants | 4 Participants | 5 Participants | 5 Participants | 8 Participants | 32 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 8 Participants | 6 Participants | 7 Participants | 6 Participants | 5 Participants | 16 Participants | 48 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 8 Participants | 10 Participants |
| Race (NIH/OMB) White | 7 Participants | 5 Participants | 6 Participants | 6 Participants | 6 Participants | 8 Participants | 38 Participants |
| Sex: Female, Male Female | 5 Participants | 2 Participants | 3 Participants | 2 Participants | 2 Participants | 4 Participants | 18 Participants |
| Sex: Female, Male Male | 4 Participants | 5 Participants | 4 Participants | 4 Participants | 5 Participants | 12 Participants | 34 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 9 / 9 | 5 / 7 | 6 / 7 | 5 / 6 | 7 / 7 | 12 / 16 |
| other Total, other adverse events | 9 / 9 | 7 / 7 | 7 / 7 | 6 / 6 | 7 / 7 | 16 / 16 |
| serious Total, serious adverse events | 4 / 9 | 4 / 7 | 3 / 7 | 3 / 6 | 4 / 7 | 12 / 16 |
Outcome results
Primary
Part A: Number of Participants Experiencing Dose Limiting Toxicities (DLTs)
A DLT is any Grade (\>=) 3 non-hematologic AE or any Grade (\>=) 4 hematologic AE according to the NCI-CTCAE v4.03, occurring during the DLT observation period that is related to either or both study drugs as determined by the Investigator or Sponsor at any dose and judged not to be related to the underlying disease or any previous or concomitant medication. The following are exceptions to the DLTs: Grade \>=3 thrombocytopenia with medically concerning bleeding; Any Grade 3 autoimmune thyroid-related toxicity that doesn't clinically resolve to \<= Grade 2 within 7 days of initiating therapy will be a DLT. Any Grade 4 neutropenia of \< 5 days duration; Grade 3 infusion-related reaction resolving within 6 hours of infusion; Grade 3 diarrhea or skin toxicity that resolves to Grade \<= 1 within 7 days after medical management; Transient Grade 3 fatigue, local reactions, flu-like symptoms; Tumor flare phenomenon of known or suspected tumor did not consider a DLT.
Time frame: Time from first treatment to final assessment up to 3 weeks
Population: DLTs analysis set included all participants who received all treatment in the DLT period or stopped treatment because of DLTs in the DLT period.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kg | Part A: Number of Participants Experiencing Dose Limiting Toxicities (DLTs) | 0 Participants |
| Part A Cohort 2: M9241 8 mcg/kg + Avelumab 10 mg/kg | Part A: Number of Participants Experiencing Dose Limiting Toxicities (DLTs) | 0 Participants |
| Part A Cohort 3: M9241 12 mcg/kg + Avelumab 10 mg/kg | Part A: Number of Participants Experiencing Dose Limiting Toxicities (DLTs) | 1 Participants |
| Part A Cohort 4: M9241 16.8 mcg/kg +Avelumab 10 mg/kg | Part A: Number of Participants Experiencing Dose Limiting Toxicities (DLTs) | 0 Participants |
| Part A Cohort 5: M9241 16.8 mcg/kg + Avelumab 800 mg | Part A: Number of Participants Experiencing Dose Limiting Toxicities (DLTs) | 0 Participants |
Primary
Part A: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment-Related TEAEs According to National Cancer Institute-Common Terminology Criteria for Adverse Event (NCI-CTCAE) v4.03
An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a product or medical device; the event needed not necessarily have a causal relationship with the treatment or usage. Serious AE: an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. TEAE: AE with onset after start of treatment or with onset date before the treatment start date but worsening after the treatment start date. TEAEs included both serious and non-serious TEAEs. Treatment-related TEAEs: reasonably related to the study intervention. Number of participants with TEAEs and treatment related TEAEs were reported.
Time frame: From first dose of study treatment up to 1311 days
Population: Safety analysis set (SAF) included all participants who receive at least 1 dose (complete or incomplete) of any investigational medicinal product (IMP) (Avelumab or NHS-IL12).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kg | Part A: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment-Related TEAEs According to National Cancer Institute-Common Terminology Criteria for Adverse Event (NCI-CTCAE) v4.03 | Participants with Treatment-related-TEAEs | 8 Participants |
| Part A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kg | Part A: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment-Related TEAEs According to National Cancer Institute-Common Terminology Criteria for Adverse Event (NCI-CTCAE) v4.03 | Participants with TEAEs | 9 Participants |
| Part A Cohort 2: M9241 8 mcg/kg + Avelumab 10 mg/kg | Part A: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment-Related TEAEs According to National Cancer Institute-Common Terminology Criteria for Adverse Event (NCI-CTCAE) v4.03 | Participants with Treatment-related-TEAEs | 5 Participants |
| Part A Cohort 2: M9241 8 mcg/kg + Avelumab 10 mg/kg | Part A: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment-Related TEAEs According to National Cancer Institute-Common Terminology Criteria for Adverse Event (NCI-CTCAE) v4.03 | Participants with TEAEs | 7 Participants |
| Part A Cohort 3: M9241 12 mcg/kg + Avelumab 10 mg/kg | Part A: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment-Related TEAEs According to National Cancer Institute-Common Terminology Criteria for Adverse Event (NCI-CTCAE) v4.03 | Participants with TEAEs | 7 Participants |
| Part A Cohort 3: M9241 12 mcg/kg + Avelumab 10 mg/kg | Part A: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment-Related TEAEs According to National Cancer Institute-Common Terminology Criteria for Adverse Event (NCI-CTCAE) v4.03 | Participants with Treatment-related-TEAEs | 6 Participants |
| Part A Cohort 4: M9241 16.8 mcg/kg +Avelumab 10 mg/kg | Part A: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment-Related TEAEs According to National Cancer Institute-Common Terminology Criteria for Adverse Event (NCI-CTCAE) v4.03 | Participants with Treatment-related-TEAEs | 5 Participants |
| Part A Cohort 4: M9241 16.8 mcg/kg +Avelumab 10 mg/kg | Part A: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment-Related TEAEs According to National Cancer Institute-Common Terminology Criteria for Adverse Event (NCI-CTCAE) v4.03 | Participants with TEAEs | 6 Participants |
| Part A Cohort 5: M9241 16.8 mcg/kg + Avelumab 800 mg | Part A: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment-Related TEAEs According to National Cancer Institute-Common Terminology Criteria for Adverse Event (NCI-CTCAE) v4.03 | Participants with TEAEs | 7 Participants |
| Part A Cohort 5: M9241 16.8 mcg/kg + Avelumab 800 mg | Part A: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment-Related TEAEs According to National Cancer Institute-Common Terminology Criteria for Adverse Event (NCI-CTCAE) v4.03 | Participants with Treatment-related-TEAEs | 6 Participants |
Primary
Part A: Number of Participants With Treatment-Related Adverse Events (TRAEs) by Severity Based on Grade 3,4 and 5 According to National Cancer Institute-Common Terminology Criteria for Adverse Events Version 4.03 (NCI-CTCAE v4.03)
AE was any untoward medical occurrence in a participants who received study drug without regard to possibility of causal relationship. An AE was considered treatment emergent if occurred for the first time after the start of study treatment or occurred prior to the start of treatment. Severity of TEAEs were graded using NCI-CTCAE v4.03 toxicity grades, as follows: Grade 3 = Severe; Grade 4 = Life-threatening and Grade 5 = Death. Number of participants with Grade 3,4 and 5 by severity were only reported.
Time frame: From first dose of study treatment up to 1311 days
Population: SAF analysis set included all participants who receive at least 1 dose (complete or incomplete) of any IMP (Avelumab or NHS-IL12).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kg | Part A: Number of Participants With Treatment-Related Adverse Events (TRAEs) by Severity Based on Grade 3,4 and 5 According to National Cancer Institute-Common Terminology Criteria for Adverse Events Version 4.03 (NCI-CTCAE v4.03) | Grade >=3 | 6 Participants |
| Part A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kg | Part A: Number of Participants With Treatment-Related Adverse Events (TRAEs) by Severity Based on Grade 3,4 and 5 According to National Cancer Institute-Common Terminology Criteria for Adverse Events Version 4.03 (NCI-CTCAE v4.03) | Grade 5 | 0 Participants |
| Part A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kg | Part A: Number of Participants With Treatment-Related Adverse Events (TRAEs) by Severity Based on Grade 3,4 and 5 According to National Cancer Institute-Common Terminology Criteria for Adverse Events Version 4.03 (NCI-CTCAE v4.03) | Grade >=4 | 2 Participants |
| Part A Cohort 2: M9241 8 mcg/kg + Avelumab 10 mg/kg | Part A: Number of Participants With Treatment-Related Adverse Events (TRAEs) by Severity Based on Grade 3,4 and 5 According to National Cancer Institute-Common Terminology Criteria for Adverse Events Version 4.03 (NCI-CTCAE v4.03) | Grade >=4 | 2 Participants |
| Part A Cohort 2: M9241 8 mcg/kg + Avelumab 10 mg/kg | Part A: Number of Participants With Treatment-Related Adverse Events (TRAEs) by Severity Based on Grade 3,4 and 5 According to National Cancer Institute-Common Terminology Criteria for Adverse Events Version 4.03 (NCI-CTCAE v4.03) | Grade >=3 | 5 Participants |
| Part A Cohort 2: M9241 8 mcg/kg + Avelumab 10 mg/kg | Part A: Number of Participants With Treatment-Related Adverse Events (TRAEs) by Severity Based on Grade 3,4 and 5 According to National Cancer Institute-Common Terminology Criteria for Adverse Events Version 4.03 (NCI-CTCAE v4.03) | Grade 5 | 1 Participants |
| Part A Cohort 3: M9241 12 mcg/kg + Avelumab 10 mg/kg | Part A: Number of Participants With Treatment-Related Adverse Events (TRAEs) by Severity Based on Grade 3,4 and 5 According to National Cancer Institute-Common Terminology Criteria for Adverse Events Version 4.03 (NCI-CTCAE v4.03) | Grade >=4 | 2 Participants |
| Part A Cohort 3: M9241 12 mcg/kg + Avelumab 10 mg/kg | Part A: Number of Participants With Treatment-Related Adverse Events (TRAEs) by Severity Based on Grade 3,4 and 5 According to National Cancer Institute-Common Terminology Criteria for Adverse Events Version 4.03 (NCI-CTCAE v4.03) | Grade >=3 | 6 Participants |
| Part A Cohort 3: M9241 12 mcg/kg + Avelumab 10 mg/kg | Part A: Number of Participants With Treatment-Related Adverse Events (TRAEs) by Severity Based on Grade 3,4 and 5 According to National Cancer Institute-Common Terminology Criteria for Adverse Events Version 4.03 (NCI-CTCAE v4.03) | Grade 5 | 0 Participants |
| Part A Cohort 4: M9241 16.8 mcg/kg +Avelumab 10 mg/kg | Part A: Number of Participants With Treatment-Related Adverse Events (TRAEs) by Severity Based on Grade 3,4 and 5 According to National Cancer Institute-Common Terminology Criteria for Adverse Events Version 4.03 (NCI-CTCAE v4.03) | Grade >=3 | 4 Participants |
| Part A Cohort 4: M9241 16.8 mcg/kg +Avelumab 10 mg/kg | Part A: Number of Participants With Treatment-Related Adverse Events (TRAEs) by Severity Based on Grade 3,4 and 5 According to National Cancer Institute-Common Terminology Criteria for Adverse Events Version 4.03 (NCI-CTCAE v4.03) | Grade 5 | 1 Participants |
| Part A Cohort 4: M9241 16.8 mcg/kg +Avelumab 10 mg/kg | Part A: Number of Participants With Treatment-Related Adverse Events (TRAEs) by Severity Based on Grade 3,4 and 5 According to National Cancer Institute-Common Terminology Criteria for Adverse Events Version 4.03 (NCI-CTCAE v4.03) | Grade >=4 | 2 Participants |
| Part A Cohort 5: M9241 16.8 mcg/kg + Avelumab 800 mg | Part A: Number of Participants With Treatment-Related Adverse Events (TRAEs) by Severity Based on Grade 3,4 and 5 According to National Cancer Institute-Common Terminology Criteria for Adverse Events Version 4.03 (NCI-CTCAE v4.03) | Grade >=4 | 1 Participants |
| Part A Cohort 5: M9241 16.8 mcg/kg + Avelumab 800 mg | Part A: Number of Participants With Treatment-Related Adverse Events (TRAEs) by Severity Based on Grade 3,4 and 5 According to National Cancer Institute-Common Terminology Criteria for Adverse Events Version 4.03 (NCI-CTCAE v4.03) | Grade >=3 | 4 Participants |
| Part A Cohort 5: M9241 16.8 mcg/kg + Avelumab 800 mg | Part A: Number of Participants With Treatment-Related Adverse Events (TRAEs) by Severity Based on Grade 3,4 and 5 According to National Cancer Institute-Common Terminology Criteria for Adverse Events Version 4.03 (NCI-CTCAE v4.03) | Grade 5 | 1 Participants |
Primary
Part B: Number of Participants With Confirmed Best Overall Response (BOR) Assessed by Investigator Using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
Confirmed BOR was defined as the best response of any of the confirmed complete response (CR), confirmed partial response (PR), stable disease (SD) and progressive disease (PD) recorded from the date of randomization until disease progression or recurrence (taking the smallest measurement recorded since the start of treatment as reference).CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30 percent (%) reduction from baseline in the sum of the longest diameter (SLD) of all lesions. Stable disease (SD)= Neither sufficient increase to qualify for progression of disease (PD) nor sufficient shrinkage to qualify for PR. PD: At least a 20 % increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions. Not evaluable (NE): No post-baseline assessment. BOR assessments were assessed by investigators.
Time frame: First dose of study drug up to 443 days
Population: Full analysis set included all participants who received at least 1 dose of any study treatment.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kg | Part B: Number of Participants With Confirmed Best Overall Response (BOR) Assessed by Investigator Using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 | Complete Response | 0 Participants |
| Part A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kg | Part B: Number of Participants With Confirmed Best Overall Response (BOR) Assessed by Investigator Using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 | Partial Response | 0 Participants |
| Part A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kg | Part B: Number of Participants With Confirmed Best Overall Response (BOR) Assessed by Investigator Using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 | Stable Disease | 2 Participants |
| Part A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kg | Part B: Number of Participants With Confirmed Best Overall Response (BOR) Assessed by Investigator Using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 | Progressive Disease | 13 Participants |
| Part A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kg | Part B: Number of Participants With Confirmed Best Overall Response (BOR) Assessed by Investigator Using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 | Not evaluable | 1 Participants |
Primary
Part B: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment-Related TEAEs According to National Cancer Institute-Common Terminology Criteria for Adverse Event (NCI-CTCAE) v4.03
An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a product or medical device; the event needed not necessarily have a causal relationship with the treatment or usage. Serious AE: an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. TEAE: AE with onset after start of treatment or with onset date before the treatment start date but worsening after the treatment start date. TEAEs included both serious and non-serious TEAEs. Treatment-related TEAEs: reasonably related to the study intervention. Number of participants with TEAEs and treatment related TEAEs were reported.
Time frame: Part B: From first dose of study treatment up to 443 days
Population: SAF included all participants who receive at least 1 dose of any investigational medicinal product (IMP) (Avelumab or NHS-IL12).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kg | Part B: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment-Related TEAEs According to National Cancer Institute-Common Terminology Criteria for Adverse Event (NCI-CTCAE) v4.03 | Participants with TEAEs | 16 Participants |
| Part A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kg | Part B: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment-Related TEAEs According to National Cancer Institute-Common Terminology Criteria for Adverse Event (NCI-CTCAE) v4.03 | Participants with Treatment-Related AEs | 15 Participants |
Primary
Part B: Number of Participants With Treatment-Related Adverse Events (TRAEs) by Severity According to National Cancer Institute-Common Terminology Criteria for Adverse Events Version 4.03 (NCI-CTCAE v4.03)
AE was any untoward medical occurrence in a participants who received study drug without regard to possibility of causal relationship. An AE was considered treatment emergent if occurred for the first time after the start of study treatment or occurred prior to the start of treatment. Severity of TEAEs were graded using NCI-CTCAE v4.03 toxicity grades, as follows: Grade 1= Mild; Grade 2 = Moderate; Grade 3 = Severe; Grade 4 = Life-threatening and Grade 5 = Death. Number of participants with TEAEs and TRAEs by severity were reported.
Time frame: First dose of study drug up to 443 days
Population: SAF analysis set included all participants who receive at least 1 dose (complete or incomplete) of any IMP (Avelumab or NHS-IL12). Here, overall number of participants analyzed signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kg | Part B: Number of Participants With Treatment-Related Adverse Events (TRAEs) by Severity According to National Cancer Institute-Common Terminology Criteria for Adverse Events Version 4.03 (NCI-CTCAE v4.03) | Any Grade | 15 Participants |
| Part A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kg | Part B: Number of Participants With Treatment-Related Adverse Events (TRAEs) by Severity According to National Cancer Institute-Common Terminology Criteria for Adverse Events Version 4.03 (NCI-CTCAE v4.03) | Grade >=3 | 8 Participants |
| Part A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kg | Part B: Number of Participants With Treatment-Related Adverse Events (TRAEs) by Severity According to National Cancer Institute-Common Terminology Criteria for Adverse Events Version 4.03 (NCI-CTCAE v4.03) | Grade >=4 | 1 Participants |
| Part A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kg | Part B: Number of Participants With Treatment-Related Adverse Events (TRAEs) by Severity According to National Cancer Institute-Common Terminology Criteria for Adverse Events Version 4.03 (NCI-CTCAE v4.03) | Grade 5 | 0 Participants |
Secondary
Part A: Apparent Terminal Half-life (t1/2) of Avelumab
Apparent terminal half-life was defined as the time required for the serum concentration of drug to decrease 50 percent in the final stage of its elimination.
Time frame: PrD, 1, 4, 8 hours PD on Day 1, 22 of cycle 1 & 2; PrD, 1 hour PD on Day 8, 15 of cycle 1 & Day 8, 15, 22 of cycle 2; PrD, 1 hour PD on Day 1 cycle 3 & Day 1, 15 of cycle 4; PrD on Day 1 of cycle 7, 10,13,16,19,22,25, & 28 (Each cycle: 28 days)
Population: Pharmacokinetic analysis set included all participants who completed at least 1 administration of avelumab and/or M9241, and who provided at least 1 sample with a measurable concentration of avelumab or M9241. Here, Overall Number of participants analyzed, signifies those participants who were evaluable for this outcome measure and Number analyzed signifies those participants who were evaluable at the specified time point.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kg | Part A: Apparent Terminal Half-life (t1/2) of Avelumab | Cycle 1 Day 1 | 94.7 hours |
| Part A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kg | Part A: Apparent Terminal Half-life (t1/2) of Avelumab | Cycle 2 Day 1 | 106 hours |
| Part A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kg | Part A: Apparent Terminal Half-life (t1/2) of Avelumab | Cycle 1 Day 15 | 101 hours |
| Part A Cohort 2: M9241 8 mcg/kg + Avelumab 10 mg/kg | Part A: Apparent Terminal Half-life (t1/2) of Avelumab | Cycle 1 Day 15 | 77.6 hours |
| Part A Cohort 2: M9241 8 mcg/kg + Avelumab 10 mg/kg | Part A: Apparent Terminal Half-life (t1/2) of Avelumab | Cycle 1 Day 1 | 87.4 hours |
| Part A Cohort 2: M9241 8 mcg/kg + Avelumab 10 mg/kg | Part A: Apparent Terminal Half-life (t1/2) of Avelumab | Cycle 2 Day 1 | 94.9 hours |
| Part A Cohort 3: M9241 12 mcg/kg + Avelumab 10 mg/kg | Part A: Apparent Terminal Half-life (t1/2) of Avelumab | Cycle 1 Day 15 | 84.1 hours |
| Part A Cohort 3: M9241 12 mcg/kg + Avelumab 10 mg/kg | Part A: Apparent Terminal Half-life (t1/2) of Avelumab | Cycle 1 Day 1 | 95.2 hours |
| Part A Cohort 3: M9241 12 mcg/kg + Avelumab 10 mg/kg | Part A: Apparent Terminal Half-life (t1/2) of Avelumab | Cycle 2 Day 1 | 80.7 hours |
| Part A Cohort 4: M9241 16.8 mcg/kg +Avelumab 10 mg/kg | Part A: Apparent Terminal Half-life (t1/2) of Avelumab | Cycle 1 Day 1 | 87.1 hours |
| Part A Cohort 4: M9241 16.8 mcg/kg +Avelumab 10 mg/kg | Part A: Apparent Terminal Half-life (t1/2) of Avelumab | Cycle 2 Day 1 | 86.2 hours |
| Part A Cohort 4: M9241 16.8 mcg/kg +Avelumab 10 mg/kg | Part A: Apparent Terminal Half-life (t1/2) of Avelumab | Cycle 1 Day 15 | 86.7 hours |
| Part A Cohort 5: M9241 16.8 mcg/kg + Avelumab 800 mg | Part A: Apparent Terminal Half-life (t1/2) of Avelumab | Cycle 1 Day 22 | 102 hours |
| Part A Cohort 5: M9241 16.8 mcg/kg + Avelumab 800 mg | Part A: Apparent Terminal Half-life (t1/2) of Avelumab | Cycle 1 Day 1 | 70.5 hours |
| Part A Cohort 5: M9241 16.8 mcg/kg + Avelumab 800 mg | Part A: Apparent Terminal Half-life (t1/2) of Avelumab | Cycle 2 Day 1 | 81.1 hours |
Secondary
Part A: Apparent Terminal Half-life (t1/2) of M9241
Apparent terminal half-life was defined as the time required for the serum concentration of drug to decrease 50 percent in the final stage of its elimination.
Time frame: PrD, 1, 4, 8 hours PD on Day 1 of cycle 1 and Day 1 of cycle 2; PrD on Day 15 of cycle 1 and cycle 2; PrD, 1 hour PD on Day 1 of cycle 3 and cycle 4; PrD on Day 1 Cycle 7, 10, 13, 16, 19, 22, 25, and 28 (Each cycle: 28 days)
Population: Pharmacokinetic analysis set included all participants who completed at least 1 administration of avelumab and/or M9241, and who provided at least 1 sample with a measurable concentration of avelumab or M9241. Here, Overall Number of participants analyzed, signifies those participants who were evaluable for this outcome measure and Number analyzed signifies those participants who were evaluable at the specified time point.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part A Cohort 2: M9241 8 mcg/kg + Avelumab 10 mg/kg | Part A: Apparent Terminal Half-life (t1/2) of M9241 | Cycle 1 Day 1 | NA hours |
| Part A Cohort 2: M9241 8 mcg/kg + Avelumab 10 mg/kg | Part A: Apparent Terminal Half-life (t1/2) of M9241 | Cycle 2 Day 1 | NA hours |
| Part A Cohort 3: M9241 12 mcg/kg + Avelumab 10 mg/kg | Part A: Apparent Terminal Half-life (t1/2) of M9241 | Cycle 1 Day 1 | NA hours |
| Part A Cohort 4: M9241 16.8 mcg/kg +Avelumab 10 mg/kg | Part A: Apparent Terminal Half-life (t1/2) of M9241 | Cycle 2 Day 1 | NA hours |
| Part A Cohort 4: M9241 16.8 mcg/kg +Avelumab 10 mg/kg | Part A: Apparent Terminal Half-life (t1/2) of M9241 | Cycle 1 Day 1 | NA hours |
| Part A Cohort 5: M9241 16.8 mcg/kg + Avelumab 800 mg | Part A: Apparent Terminal Half-life (t1/2) of M9241 | Cycle 1 Day 1 | 161 hours |
| Part A Cohort 5: M9241 16.8 mcg/kg + Avelumab 800 mg | Part A: Apparent Terminal Half-life (t1/2) of M9241 | Cycle 2 Day 1 | 84.4 hours |
Secondary
Part A: Area Under Serum Concentration Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Avelumab
The AUC(0-inf) was estimated by determining the total area under the curve of the concentration versus time curve extrapolated to infinity.
Time frame: PrD, 1, 4, 8 hours PD on Day 1, 22 of cycle 1 & 2; PrD, 1 hour PD on Day 8, 15 of cycle 1 & Day 8, 15, 22 of cycle 2; PrD, 1 hour PD on Day 1 cycle 3 & Day 1, 15 of cycle 4; PrD on Day 1 of cycle 7, 10,13,16,19,22,25, & 28 (Each cycle: 28 days)
Population: Pharmacokinetic analysis set included all participants who completed at least 1 administration of avelumab and/or M9241, and who provided at least 1 sample with a measurable concentration of avelumab or M9241. Here, Overall Number of participants analyzed, signifies those participants who were evaluable for this outcome measure and Number analyzed signifies those participants who were evaluable at the specified time point.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kg | Part A: Area Under Serum Concentration Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Avelumab | Cycle 1 Day 1 | 22300 microgram*hour per milliliter (mcg*h/mL) | Geometric Coefficient of Variation 41.5 |
| Part A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kg | Part A: Area Under Serum Concentration Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Avelumab | Cycle 2 Day 1 | 29800 microgram*hour per milliliter (mcg*h/mL) | Geometric Coefficient of Variation 18.4 |
| Part A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kg | Part A: Area Under Serum Concentration Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Avelumab | Cycle 1 Day 15 | 26300 microgram*hour per milliliter (mcg*h/mL) | Geometric Coefficient of Variation 37.2 |
| Part A Cohort 2: M9241 8 mcg/kg + Avelumab 10 mg/kg | Part A: Area Under Serum Concentration Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Avelumab | Cycle 1 Day 15 | 29800 microgram*hour per milliliter (mcg*h/mL) | Geometric Coefficient of Variation 35.7 |
| Part A Cohort 2: M9241 8 mcg/kg + Avelumab 10 mg/kg | Part A: Area Under Serum Concentration Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Avelumab | Cycle 1 Day 1 | 30100 microgram*hour per milliliter (mcg*h/mL) | Geometric Coefficient of Variation 75.8 |
| Part A Cohort 2: M9241 8 mcg/kg + Avelumab 10 mg/kg | Part A: Area Under Serum Concentration Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Avelumab | Cycle 2 Day 1 | 33100 microgram*hour per milliliter (mcg*h/mL) | Geometric Coefficient of Variation 48.4 |
| Part A Cohort 3: M9241 12 mcg/kg + Avelumab 10 mg/kg | Part A: Area Under Serum Concentration Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Avelumab | Cycle 1 Day 15 | 27100 microgram*hour per milliliter (mcg*h/mL) | Geometric Coefficient of Variation 34.5 |
| Part A Cohort 3: M9241 12 mcg/kg + Avelumab 10 mg/kg | Part A: Area Under Serum Concentration Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Avelumab | Cycle 1 Day 1 | 26500 microgram*hour per milliliter (mcg*h/mL) | Geometric Coefficient of Variation 21.5 |
| Part A Cohort 3: M9241 12 mcg/kg + Avelumab 10 mg/kg | Part A: Area Under Serum Concentration Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Avelumab | Cycle 2 Day 1 | 24300 microgram*hour per milliliter (mcg*h/mL) | Geometric Coefficient of Variation 30.6 |
| Part A Cohort 4: M9241 16.8 mcg/kg +Avelumab 10 mg/kg | Part A: Area Under Serum Concentration Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Avelumab | Cycle 1 Day 1 | 18800 microgram*hour per milliliter (mcg*h/mL) | Geometric Coefficient of Variation 29.5 |
| Part A Cohort 4: M9241 16.8 mcg/kg +Avelumab 10 mg/kg | Part A: Area Under Serum Concentration Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Avelumab | Cycle 2 Day 1 | 24400 microgram*hour per milliliter (mcg*h/mL) | Geometric Coefficient of Variation 13.3 |
| Part A Cohort 4: M9241 16.8 mcg/kg +Avelumab 10 mg/kg | Part A: Area Under Serum Concentration Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Avelumab | Cycle 1 Day 15 | 23000 microgram*hour per milliliter (mcg*h/mL) | Geometric Coefficient of Variation 26 |
| Part A Cohort 5: M9241 16.8 mcg/kg + Avelumab 800 mg | Part A: Area Under Serum Concentration Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Avelumab | Cycle 1 Day 22 | 43400 microgram*hour per milliliter (mcg*h/mL) | Geometric Coefficient of Variation 56.1 |
| Part A Cohort 5: M9241 16.8 mcg/kg + Avelumab 800 mg | Part A: Area Under Serum Concentration Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Avelumab | Cycle 1 Day 1 | 27000 microgram*hour per milliliter (mcg*h/mL) | Geometric Coefficient of Variation 65 |
| Part A Cohort 5: M9241 16.8 mcg/kg + Avelumab 800 mg | Part A: Area Under Serum Concentration Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Avelumab | Cycle 2 Day 1 | 35100 microgram*hour per milliliter (mcg*h/mL) | Geometric Coefficient of Variation 40.3 |
Secondary
Part A: Area Under Serum Concentration Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of M9241
The AUC(0-inf) was estimated by determining the total area under the curve of the concentration versus time curve extrapolated to infinity.
Time frame: PrD, 1, 4, 8 hours PD on Day 1 of cycle 1 and Day 1 of cycle 2; PrD on Day 15 of cycle 1 and cycle 2; PrD, 1hour PD on Day 1 of cycle 3 and cycle 4; PrD on Day 1 Cycle 7, 10, 13, 16, 19, 22, 25, and 28 (Each cycle: 28 days)
Population: Pharmacokinetic analysis set included participants who completed at least 1 administration of avelumab and/or M9241 and provided at least 1 sample with a measurable concentration. Here, Overall Number of participants analyzed, signifies participants evaluable for this outcome measure and Number analyzed signifies participants evaluable at the specified time point. None of the participants were analyzed in Part A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kg arm at specified timepoints.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A Cohort 2: M9241 8 mcg/kg + Avelumab 10 mg/kg | Part A: Area Under Serum Concentration Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of M9241 | Cycle 1 Day 1 | NA ng*h/mL | — |
| Part A Cohort 2: M9241 8 mcg/kg + Avelumab 10 mg/kg | Part A: Area Under Serum Concentration Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of M9241 | Cycle 2 Day 1 | NA ng*h/mL | — |
| Part A Cohort 3: M9241 12 mcg/kg + Avelumab 10 mg/kg | Part A: Area Under Serum Concentration Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of M9241 | Cycle 1 Day 1 | NA ng*h/mL | — |
| Part A Cohort 4: M9241 16.8 mcg/kg +Avelumab 10 mg/kg | Part A: Area Under Serum Concentration Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of M9241 | Cycle 1 Day 1 | NA ng*h/mL | — |
| Part A Cohort 4: M9241 16.8 mcg/kg +Avelumab 10 mg/kg | Part A: Area Under Serum Concentration Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of M9241 | Cycle 2 Day 1 | NA ng*h/mL | — |
| Part A Cohort 5: M9241 16.8 mcg/kg + Avelumab 800 mg | Part A: Area Under Serum Concentration Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of M9241 | Cycle 2 Day 1 | 2860 ng*h/mL | Geometric Coefficient of Variation 19.9 |
| Part A Cohort 5: M9241 16.8 mcg/kg + Avelumab 800 mg | Part A: Area Under Serum Concentration Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of M9241 | Cycle 1 Day 1 | 2370 ng*h/mL | Geometric Coefficient of Variation 31.5 |
Secondary
Part A: Area Under Serum Concentration Time Curve From Time Zero to the Time of the Last Observation (AUC0-t) of Avelumab
Area under the serum concentration versus time curve from time zero to the last sampling time t at which concentration is at or above the lower limit of quantification (LLLQ). AUC0-t was calculated according to the mixed log-linear trapezoidal rule.
Time frame: Predose (PrD),1,4,8 hours postdose (PD) on Day 1,22 of Cycle 1 & 2; PrD,1 hour PD on Day 8,15 of Cycle 1 & Day 8,15,22 of Cycle 2; PrD, 1 hour PD on Day 1 Cycle 3 & Day 1,15 of Cycle 4; PrD on Day 1 of Cycle 7,10,13,16,19,22,25, & 28 (Each cycle: 28 days)
Population: Pharmacokinetic analysis set included all participants who completed at least 1 administration of avelumab and/or M9241, and who provided at least 1 sample with a measurable concentration of avelumab or M9241. Here, Overall Number of participants analyzed, signifies those participants who were evaluable for this outcome measure and Number analyzed signifies those participants who were evaluable at the specified time point.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kg | Part A: Area Under Serum Concentration Time Curve From Time Zero to the Time of the Last Observation (AUC0-t) of Avelumab | Cycle 2 Day 1 | 26400 microgram*hour per milliliter (mcg*h/mL) | Geometric Coefficient of Variation 17.2 |
| Part A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kg | Part A: Area Under Serum Concentration Time Curve From Time Zero to the Time of the Last Observation (AUC0-t) of Avelumab | Cycle 1 Day 15 | 22800 microgram*hour per milliliter (mcg*h/mL) | Geometric Coefficient of Variation 40.5 |
| Part A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kg | Part A: Area Under Serum Concentration Time Curve From Time Zero to the Time of the Last Observation (AUC0-t) of Avelumab | Cycle 1 Day 1 | 20700 microgram*hour per milliliter (mcg*h/mL) | Geometric Coefficient of Variation 38.1 |
| Part A Cohort 2: M9241 8 mcg/kg + Avelumab 10 mg/kg | Part A: Area Under Serum Concentration Time Curve From Time Zero to the Time of the Last Observation (AUC0-t) of Avelumab | Cycle 2 Day 1 | 27900 microgram*hour per milliliter (mcg*h/mL) | Geometric Coefficient of Variation 47.9 |
| Part A Cohort 2: M9241 8 mcg/kg + Avelumab 10 mg/kg | Part A: Area Under Serum Concentration Time Curve From Time Zero to the Time of the Last Observation (AUC0-t) of Avelumab | Cycle 1 Day 1 | 26600 microgram*hour per milliliter (mcg*h/mL) | Geometric Coefficient of Variation 57.9 |
| Part A Cohort 2: M9241 8 mcg/kg + Avelumab 10 mg/kg | Part A: Area Under Serum Concentration Time Curve From Time Zero to the Time of the Last Observation (AUC0-t) of Avelumab | Cycle 1 Day 15 | 26100 microgram*hour per milliliter (mcg*h/mL) | Geometric Coefficient of Variation 42.5 |
| Part A Cohort 3: M9241 12 mcg/kg + Avelumab 10 mg/kg | Part A: Area Under Serum Concentration Time Curve From Time Zero to the Time of the Last Observation (AUC0-t) of Avelumab | Cycle 1 Day 1 | 23600 microgram*hour per milliliter (mcg*h/mL) | Geometric Coefficient of Variation 16.6 |
| Part A Cohort 3: M9241 12 mcg/kg + Avelumab 10 mg/kg | Part A: Area Under Serum Concentration Time Curve From Time Zero to the Time of the Last Observation (AUC0-t) of Avelumab | Cycle 1 Day 15 | 28300 microgram*hour per milliliter (mcg*h/mL) | Geometric Coefficient of Variation 39.4 |
| Part A Cohort 3: M9241 12 mcg/kg + Avelumab 10 mg/kg | Part A: Area Under Serum Concentration Time Curve From Time Zero to the Time of the Last Observation (AUC0-t) of Avelumab | Cycle 2 Day 1 | 22700 microgram*hour per milliliter (mcg*h/mL) | Geometric Coefficient of Variation 23.2 |
| Part A Cohort 4: M9241 16.8 mcg/kg +Avelumab 10 mg/kg | Part A: Area Under Serum Concentration Time Curve From Time Zero to the Time of the Last Observation (AUC0-t) of Avelumab | Cycle 1 Day 15 | 22000 microgram*hour per milliliter (mcg*h/mL) | Geometric Coefficient of Variation 19.2 |
| Part A Cohort 4: M9241 16.8 mcg/kg +Avelumab 10 mg/kg | Part A: Area Under Serum Concentration Time Curve From Time Zero to the Time of the Last Observation (AUC0-t) of Avelumab | Cycle 1 Day 1 | 17400 microgram*hour per milliliter (mcg*h/mL) | Geometric Coefficient of Variation 33.4 |
| Part A Cohort 4: M9241 16.8 mcg/kg +Avelumab 10 mg/kg | Part A: Area Under Serum Concentration Time Curve From Time Zero to the Time of the Last Observation (AUC0-t) of Avelumab | Cycle 2 Day 1 | 22700 microgram*hour per milliliter (mcg*h/mL) | Geometric Coefficient of Variation 10.5 |
| Part A Cohort 5: M9241 16.8 mcg/kg + Avelumab 800 mg | Part A: Area Under Serum Concentration Time Curve From Time Zero to the Time of the Last Observation (AUC0-t) of Avelumab | Cycle 1 Day 1 | 17900 microgram*hour per milliliter (mcg*h/mL) | Geometric Coefficient of Variation 39.7 |
| Part A Cohort 5: M9241 16.8 mcg/kg + Avelumab 800 mg | Part A: Area Under Serum Concentration Time Curve From Time Zero to the Time of the Last Observation (AUC0-t) of Avelumab | Cycle 4 Day 1 | NA microgram*hour per milliliter (mcg*h/mL) | — |
| Part A Cohort 5: M9241 16.8 mcg/kg + Avelumab 800 mg | Part A: Area Under Serum Concentration Time Curve From Time Zero to the Time of the Last Observation (AUC0-t) of Avelumab | Cycle 2 Day 1 | 22100 microgram*hour per milliliter (mcg*h/mL) | Geometric Coefficient of Variation 42.7 |
| Part A Cohort 5: M9241 16.8 mcg/kg + Avelumab 800 mg | Part A: Area Under Serum Concentration Time Curve From Time Zero to the Time of the Last Observation (AUC0-t) of Avelumab | Cycle 1 Day 22 | 26300 microgram*hour per milliliter (mcg*h/mL) | Geometric Coefficient of Variation 31 |
Secondary
Part A: Area Under Serum Concentration Time Curve From Time Zero to the Time of the Last Observation (AUC0-t) of M9241
Area under the serum concentration versus time curve from time zero to the last sampling time t at which the concentration is at or above the lower limit of quantification (LLLQ). (AUC0-t) was calculated according to the mixed log-linear trapezoidal rule.
Time frame: PrD, 1, 4, 8 hours PD on Day 1 of cycle 1 and Day 1 of cycle 2; PrD on Day 15 of cycle 1 and cycle 2; PrD, 1hour PD on Day 1 of cycle 3 and cycle 4; PrD on Day 1 Cycle 7, 10, 13, 16, 19, 22, 25, and 28 (Each cycle: 28 days)
Population: Pharmacokinetic analysis set included all participants who completed at least 1 administration of avelumab and/or M9241, and who provided at least 1 sample with a measurable concentration of avelumab or M9241. Here, Overall Number of participants analyzed, signifies those participants who were evaluable for this outcome measure and Number analyzed signifies those participants who were evaluable at the specified time point.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kg | Part A: Area Under Serum Concentration Time Curve From Time Zero to the Time of the Last Observation (AUC0-t) of M9241 | Cycle 1 Day 1 | 105 nanogram*hour/milliliter (ng*h/mL) | Geometric Coefficient of Variation 114.4 |
| Part A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kg | Part A: Area Under Serum Concentration Time Curve From Time Zero to the Time of the Last Observation (AUC0-t) of M9241 | Cycle 2 Day 1 | 183 nanogram*hour/milliliter (ng*h/mL) | Geometric Coefficient of Variation 151.7 |
| Part A Cohort 2: M9241 8 mcg/kg + Avelumab 10 mg/kg | Part A: Area Under Serum Concentration Time Curve From Time Zero to the Time of the Last Observation (AUC0-t) of M9241 | Cycle 1 Day 1 | 421 nanogram*hour/milliliter (ng*h/mL) | Geometric Coefficient of Variation 82.9 |
| Part A Cohort 2: M9241 8 mcg/kg + Avelumab 10 mg/kg | Part A: Area Under Serum Concentration Time Curve From Time Zero to the Time of the Last Observation (AUC0-t) of M9241 | Cycle 2 Day 1 | 306 nanogram*hour/milliliter (ng*h/mL) | Geometric Coefficient of Variation 132.6 |
| Part A Cohort 3: M9241 12 mcg/kg + Avelumab 10 mg/kg | Part A: Area Under Serum Concentration Time Curve From Time Zero to the Time of the Last Observation (AUC0-t) of M9241 | Cycle 2 Day 1 | 184 nanogram*hour/milliliter (ng*h/mL) | Geometric Coefficient of Variation 174 |
| Part A Cohort 3: M9241 12 mcg/kg + Avelumab 10 mg/kg | Part A: Area Under Serum Concentration Time Curve From Time Zero to the Time of the Last Observation (AUC0-t) of M9241 | Cycle 1 Day 1 | 661 nanogram*hour/milliliter (ng*h/mL) | Geometric Coefficient of Variation 58.2 |
| Part A Cohort 4: M9241 16.8 mcg/kg +Avelumab 10 mg/kg | Part A: Area Under Serum Concentration Time Curve From Time Zero to the Time of the Last Observation (AUC0-t) of M9241 | Cycle 1 Day 1 | 621 nanogram*hour/milliliter (ng*h/mL) | Geometric Coefficient of Variation 96.5 |
| Part A Cohort 4: M9241 16.8 mcg/kg +Avelumab 10 mg/kg | Part A: Area Under Serum Concentration Time Curve From Time Zero to the Time of the Last Observation (AUC0-t) of M9241 | Cycle 2 Day 1 | 1250 nanogram*hour/milliliter (ng*h/mL) | Geometric Coefficient of Variation 46.2 |
| Part A Cohort 5: M9241 16.8 mcg/kg + Avelumab 800 mg | Part A: Area Under Serum Concentration Time Curve From Time Zero to the Time of the Last Observation (AUC0-t) of M9241 | Cycle 1 Day 1 | 873 nanogram*hour/milliliter (ng*h/mL) | Geometric Coefficient of Variation 264 |
| Part A Cohort 5: M9241 16.8 mcg/kg + Avelumab 800 mg | Part A: Area Under Serum Concentration Time Curve From Time Zero to the Time of the Last Observation (AUC0-t) of M9241 | Cycle 2 Day 1 | 1060 nanogram*hour/milliliter (ng*h/mL) | Geometric Coefficient of Variation 308.8 |
| Part A Cohort 5: M9241 16.8 mcg/kg + Avelumab 800 mg | Part A: Area Under Serum Concentration Time Curve From Time Zero to the Time of the Last Observation (AUC0-t) of M9241 | Cycle 4 Day 1 | NA nanogram*hour/milliliter (ng*h/mL) | — |
Secondary
Part A: Area Under the Serum Concentration-Time Curve Within One Dosing Interval (AUC0-tau) of Avelumab
AUCtau was defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).
Time frame: PrD, 1, 4, 8 hours PD on Day 1, 22 of cycle 1 & 2; PrD, 1 hour PD on Day 8, 15 of cycle 1 & Day 8, 15, 22 of cycle 2; PrD, 1 hour PD on Day 1 cycle 3 & Day 1, 15 of cycle 4; PrD on Day 1 of cycle 7, 10,13,16,19,22,25, & 28 (Each cycle: 28 days)
Population: Pharmacokinetic analysis set included all participants who completed at least 1 administration of avelumab and/or M9241, and who provided at least 1 sample with a measurable concentration of avelumab or M9241. Here, Overall Number of participants analyzed, signifies those participants who were evaluable for this outcome measure and Number analyzed signifies those participants who were evaluable at the specified time point.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kg | Part A: Area Under the Serum Concentration-Time Curve Within One Dosing Interval (AUC0-tau) of Avelumab | Cycle 2 Day 1 | 26400 mcg*h/mL | Geometric Coefficient of Variation 17.4 |
| Part A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kg | Part A: Area Under the Serum Concentration-Time Curve Within One Dosing Interval (AUC0-tau) of Avelumab | Cycle 1 Day 15 | 24100 mcg*h/mL | Geometric Coefficient of Variation 35 |
| Part A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kg | Part A: Area Under the Serum Concentration-Time Curve Within One Dosing Interval (AUC0-tau) of Avelumab | Cycle 1 Day 1 | 20900 mcg*h/mL | Geometric Coefficient of Variation 37.6 |
| Part A Cohort 2: M9241 8 mcg/kg + Avelumab 10 mg/kg | Part A: Area Under the Serum Concentration-Time Curve Within One Dosing Interval (AUC0-tau) of Avelumab | Cycle 2 Day 1 | 29500 mcg*h/mL | Geometric Coefficient of Variation 37.6 |
| Part A Cohort 2: M9241 8 mcg/kg + Avelumab 10 mg/kg | Part A: Area Under the Serum Concentration-Time Curve Within One Dosing Interval (AUC0-tau) of Avelumab | Cycle 1 Day 15 | 27600 mcg*h/mL | Geometric Coefficient of Variation 33.1 |
| Part A Cohort 2: M9241 8 mcg/kg + Avelumab 10 mg/kg | Part A: Area Under the Serum Concentration-Time Curve Within One Dosing Interval (AUC0-tau) of Avelumab | Cycle 1 Day 1 | 26700 mcg*h/mL | Geometric Coefficient of Variation 58.3 |
| Part A Cohort 3: M9241 12 mcg/kg + Avelumab 10 mg/kg | Part A: Area Under the Serum Concentration-Time Curve Within One Dosing Interval (AUC0-tau) of Avelumab | Cycle 1 Day 1 | 24500 mcg*h/mL | Geometric Coefficient of Variation 19.2 |
| Part A Cohort 3: M9241 12 mcg/kg + Avelumab 10 mg/kg | Part A: Area Under the Serum Concentration-Time Curve Within One Dosing Interval (AUC0-tau) of Avelumab | Cycle 1 Day 15 | 28300 mcg*h/mL | Geometric Coefficient of Variation 39.4 |
| Part A Cohort 3: M9241 12 mcg/kg + Avelumab 10 mg/kg | Part A: Area Under the Serum Concentration-Time Curve Within One Dosing Interval (AUC0-tau) of Avelumab | Cycle 2 Day 1 | 22900 mcg*h/mL | Geometric Coefficient of Variation 27.1 |
| Part A Cohort 4: M9241 16.8 mcg/kg +Avelumab 10 mg/kg | Part A: Area Under the Serum Concentration-Time Curve Within One Dosing Interval (AUC0-tau) of Avelumab | Cycle 1 Day 15 | 21400 mcg*h/mL | Geometric Coefficient of Variation 24.2 |
| Part A Cohort 4: M9241 16.8 mcg/kg +Avelumab 10 mg/kg | Part A: Area Under the Serum Concentration-Time Curve Within One Dosing Interval (AUC0-tau) of Avelumab | Cycle 1 Day 1 | 17400 mcg*h/mL | Geometric Coefficient of Variation 33.1 |
| Part A Cohort 4: M9241 16.8 mcg/kg +Avelumab 10 mg/kg | Part A: Area Under the Serum Concentration-Time Curve Within One Dosing Interval (AUC0-tau) of Avelumab | Cycle 2 Day 1 | 22800 mcg*h/mL | Geometric Coefficient of Variation 11.6 |
| Part A Cohort 5: M9241 16.8 mcg/kg + Avelumab 800 mg | Part A: Area Under the Serum Concentration-Time Curve Within One Dosing Interval (AUC0-tau) of Avelumab | Cycle 4 Day 1 | NA mcg*h/mL | — |
| Part A Cohort 5: M9241 16.8 mcg/kg + Avelumab 800 mg | Part A: Area Under the Serum Concentration-Time Curve Within One Dosing Interval (AUC0-tau) of Avelumab | Cycle 1 Day 22 | 27500 mcg*h/mL | Geometric Coefficient of Variation 34.7 |
| Part A Cohort 5: M9241 16.8 mcg/kg + Avelumab 800 mg | Part A: Area Under the Serum Concentration-Time Curve Within One Dosing Interval (AUC0-tau) of Avelumab | Cycle 1 Day 1 | 19800 mcg*h/mL | Geometric Coefficient of Variation 44.7 |
| Part A Cohort 5: M9241 16.8 mcg/kg + Avelumab 800 mg | Part A: Area Under the Serum Concentration-Time Curve Within One Dosing Interval (AUC0-tau) of Avelumab | Cycle 2 Day 1 | 25500 mcg*h/mL | Geometric Coefficient of Variation 26.1 |
Secondary
Part A: Area Under the Serum Concentration-Time Curve Within One Dosing Interval (AUC0-tau) of M9241
AUCtau was defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).
Time frame: PrD, 1, 4, 8 hours PD on Day 1 of cycle 1 and Day 1 of cycle 2; PrD on Day 15 of cycle 1 and cycle 2; PrD, 1 hour PD on Day 1 of cycle 3 and cycle 4; PrD on Day 1 Cycle 7, 10, 13, 16, 19, 22, 25, and 28 (Each cycle: 28 days)
Population: Pharmacokinetic analysis set included participants who completed at least 1 administration of avelumab and/or M9241 and provided at least 1 sample with a measurable concentration. Here, Overall Number of participants analyzed, signifies participants evaluable for this outcome measure and Number analyzed signifies participants evaluable at the specified time point. None of the participants were analyzed in Part A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kg arm at specified timepoints.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A Cohort 2: M9241 8 mcg/kg + Avelumab 10 mg/kg | Part A: Area Under the Serum Concentration-Time Curve Within One Dosing Interval (AUC0-tau) of M9241 | Cycle 1 Day 1 | NA ng*h/mL | — |
| Part A Cohort 2: M9241 8 mcg/kg + Avelumab 10 mg/kg | Part A: Area Under the Serum Concentration-Time Curve Within One Dosing Interval (AUC0-tau) of M9241 | Cycle 2 Day 1 | NA ng*h/mL | — |
| Part A Cohort 3: M9241 12 mcg/kg + Avelumab 10 mg/kg | Part A: Area Under the Serum Concentration-Time Curve Within One Dosing Interval (AUC0-tau) of M9241 | Cycle 2 Day 1 | NA ng*h/mL | — |
| Part A Cohort 3: M9241 12 mcg/kg + Avelumab 10 mg/kg | Part A: Area Under the Serum Concentration-Time Curve Within One Dosing Interval (AUC0-tau) of M9241 | Cycle 1 Day 1 | NA ng*h/mL | — |
| Part A Cohort 4: M9241 16.8 mcg/kg +Avelumab 10 mg/kg | Part A: Area Under the Serum Concentration-Time Curve Within One Dosing Interval (AUC0-tau) of M9241 | Cycle 1 Day 1 | 835 ng*h/mL | Geometric Coefficient of Variation 64.3 |
| Part A Cohort 4: M9241 16.8 mcg/kg +Avelumab 10 mg/kg | Part A: Area Under the Serum Concentration-Time Curve Within One Dosing Interval (AUC0-tau) of M9241 | Cycle 2 Day 1 | NA ng*h/mL | — |
| Part A Cohort 5: M9241 16.8 mcg/kg + Avelumab 800 mg | Part A: Area Under the Serum Concentration-Time Curve Within One Dosing Interval (AUC0-tau) of M9241 | Cycle 1 Day 1 | 2130 ng*h/mL | Geometric Coefficient of Variation 35.6 |
| Part A Cohort 5: M9241 16.8 mcg/kg + Avelumab 800 mg | Part A: Area Under the Serum Concentration-Time Curve Within One Dosing Interval (AUC0-tau) of M9241 | Cycle 2 Day 1 | 2390 ng*h/mL | Geometric Coefficient of Variation 80.4 |
Secondary
Part A: Maximum Observed Serum Concentration (Cmax) of Avelumab
Cmax is the maximum observed serum concentration obtained directly from the concentration versus time curve.
Time frame: PrD, 1, 4, 8 hours PD on Day 1, 22 of cycle 1 & 2; PrD, 1 hour PD on Day 8, 15 of cycle 1 & Day 8, 15, 22 of cycle 2; PrD, 1 hour PD on Day 1 cycle 3 & Day 1, 15 of cycle 4; PrD on Day 1 of cycle 7, 10,13,16,19,22,25, & 28 (Each cycle: 28 days)
Population: Pharmacokinetic analysis set included all participants who completed at least 1 administration of avelumab and/or M9241, and who provided at least 1 sample with a measurable concentration of avelumab or M9241. Here, Overall Number of participants analyzed, signifies those participants who were evaluable for this outcome measure and Number analyzed signifies those participants who were evaluable at the specified time point.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kg | Part A: Maximum Observed Serum Concentration (Cmax) of Avelumab | Cycle 1 Day 15 | 229 microgram/milliliter (mcg/mL) | Geometric Coefficient of Variation 54.4 |
| Part A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kg | Part A: Maximum Observed Serum Concentration (Cmax) of Avelumab | Cycle 2 Day 1 | 213 microgram/milliliter (mcg/mL) | Geometric Coefficient of Variation 21.3 |
| Part A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kg | Part A: Maximum Observed Serum Concentration (Cmax) of Avelumab | Cycle 1 Day 1 | 241 microgram/milliliter (mcg/mL) | Geometric Coefficient of Variation 39.9 |
| Part A Cohort 2: M9241 8 mcg/kg + Avelumab 10 mg/kg | Part A: Maximum Observed Serum Concentration (Cmax) of Avelumab | Cycle 1 Day 15 | 250 microgram/milliliter (mcg/mL) | Geometric Coefficient of Variation 14.6 |
| Part A Cohort 2: M9241 8 mcg/kg + Avelumab 10 mg/kg | Part A: Maximum Observed Serum Concentration (Cmax) of Avelumab | Cycle 2 Day 1 | 249 microgram/milliliter (mcg/mL) | Geometric Coefficient of Variation 37.5 |
| Part A Cohort 2: M9241 8 mcg/kg + Avelumab 10 mg/kg | Part A: Maximum Observed Serum Concentration (Cmax) of Avelumab | Cycle 1 Day 1 | 244 microgram/milliliter (mcg/mL) | Geometric Coefficient of Variation 29.9 |
| Part A Cohort 3: M9241 12 mcg/kg + Avelumab 10 mg/kg | Part A: Maximum Observed Serum Concentration (Cmax) of Avelumab | Cycle 1 Day 15 | 256 microgram/milliliter (mcg/mL) | Geometric Coefficient of Variation 32 |
| Part A Cohort 3: M9241 12 mcg/kg + Avelumab 10 mg/kg | Part A: Maximum Observed Serum Concentration (Cmax) of Avelumab | Cycle 1 Day 1 | 287 microgram/milliliter (mcg/mL) | Geometric Coefficient of Variation 36.4 |
| Part A Cohort 3: M9241 12 mcg/kg + Avelumab 10 mg/kg | Part A: Maximum Observed Serum Concentration (Cmax) of Avelumab | Cycle 2 Day 1 | 210 microgram/milliliter (mcg/mL) | Geometric Coefficient of Variation 19.7 |
| Part A Cohort 4: M9241 16.8 mcg/kg +Avelumab 10 mg/kg | Part A: Maximum Observed Serum Concentration (Cmax) of Avelumab | Cycle 2 Day 1 | 200 microgram/milliliter (mcg/mL) | Geometric Coefficient of Variation 8.1 |
| Part A Cohort 4: M9241 16.8 mcg/kg +Avelumab 10 mg/kg | Part A: Maximum Observed Serum Concentration (Cmax) of Avelumab | Cycle 1 Day 15 | 201 microgram/milliliter (mcg/mL) | Geometric Coefficient of Variation 25.6 |
| Part A Cohort 4: M9241 16.8 mcg/kg +Avelumab 10 mg/kg | Part A: Maximum Observed Serum Concentration (Cmax) of Avelumab | Cycle 1 Day 1 | 156 microgram/milliliter (mcg/mL) | Geometric Coefficient of Variation 67.7 |
| Part A Cohort 5: M9241 16.8 mcg/kg + Avelumab 800 mg | Part A: Maximum Observed Serum Concentration (Cmax) of Avelumab | Cycle 1 Day 1 | 228 microgram/milliliter (mcg/mL) | Geometric Coefficient of Variation 29.3 |
| Part A Cohort 5: M9241 16.8 mcg/kg + Avelumab 800 mg | Part A: Maximum Observed Serum Concentration (Cmax) of Avelumab | Cycle 4 Day 1 | NA microgram/milliliter (mcg/mL) | — |
| Part A Cohort 5: M9241 16.8 mcg/kg + Avelumab 800 mg | Part A: Maximum Observed Serum Concentration (Cmax) of Avelumab | Cycle 1 Day 22 | 269 microgram/milliliter (mcg/mL) | Geometric Coefficient of Variation 44 |
| Part A Cohort 5: M9241 16.8 mcg/kg + Avelumab 800 mg | Part A: Maximum Observed Serum Concentration (Cmax) of Avelumab | Cycle 2 Day 1 | 318 microgram/milliliter (mcg/mL) | Geometric Coefficient of Variation 33.5 |
Secondary
Part A: Maximum Observed Serum Concentration (Cmax) of M9241
Cmax is the maximum observed serum concentration obtained directly from the concentration versus time curve.
Time frame: PrD, 1, 4, 8 hours PD on Day 1 of cycle 1 and Day 1 of cycle 2; PrD on Day 15 of cycle 1 and cycle 2; PrD, 1 hour PD on Day 1 of cycle 3 and cycle 4; PrD on Day 1 Cycle 7, 10, 13, 16, 19, 22, 25, and 28 (Each cycle: 28 days)
Population: Pharmacokinetic analysis set included all participants who completed at least 1 administration of avelumab and/or M9241, and who provided at least 1 sample with a measurable concentration of avelumab or M9241. Here, Overall Number of participants analyzed, signifies those participants who were evaluable for this outcome measure and Number analyzed signifies those participants who were evaluable at the specified time point.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kg | Part A: Maximum Observed Serum Concentration (Cmax) of M9241 | Cycle 1 Day 1 | 2.79 ng/mL | Geometric Coefficient of Variation 79.1 |
| Part A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kg | Part A: Maximum Observed Serum Concentration (Cmax) of M9241 | Cycle 2 Day 1 | 2.68 ng/mL | Geometric Coefficient of Variation 45.7 |
| Part A Cohort 2: M9241 8 mcg/kg + Avelumab 10 mg/kg | Part A: Maximum Observed Serum Concentration (Cmax) of M9241 | Cycle 1 Day 1 | 4.42 ng/mL | Geometric Coefficient of Variation 84.9 |
| Part A Cohort 2: M9241 8 mcg/kg + Avelumab 10 mg/kg | Part A: Maximum Observed Serum Concentration (Cmax) of M9241 | Cycle 2 Day 1 | 3.81 ng/mL | Geometric Coefficient of Variation 39.4 |
| Part A Cohort 3: M9241 12 mcg/kg + Avelumab 10 mg/kg | Part A: Maximum Observed Serum Concentration (Cmax) of M9241 | Cycle 2 Day 1 | 4.45 ng/mL | Geometric Coefficient of Variation 112.8 |
| Part A Cohort 3: M9241 12 mcg/kg + Avelumab 10 mg/kg | Part A: Maximum Observed Serum Concentration (Cmax) of M9241 | Cycle 1 Day 1 | 12.6 ng/mL | Geometric Coefficient of Variation 40.9 |
| Part A Cohort 4: M9241 16.8 mcg/kg +Avelumab 10 mg/kg | Part A: Maximum Observed Serum Concentration (Cmax) of M9241 | Cycle 1 Day 1 | 5.91 ng/mL | Geometric Coefficient of Variation 54.8 |
| Part A Cohort 4: M9241 16.8 mcg/kg +Avelumab 10 mg/kg | Part A: Maximum Observed Serum Concentration (Cmax) of M9241 | Cycle 2 Day 1 | 9.42 ng/mL | Geometric Coefficient of Variation 63.3 |
| Part A Cohort 5: M9241 16.8 mcg/kg + Avelumab 800 mg | Part A: Maximum Observed Serum Concentration (Cmax) of M9241 | Cycle 1 Day 1 | 6.88 ng/mL | Geometric Coefficient of Variation 99.6 |
| Part A Cohort 5: M9241 16.8 mcg/kg + Avelumab 800 mg | Part A: Maximum Observed Serum Concentration (Cmax) of M9241 | Cycle 2 Day 1 | 10.4 ng/mL | Geometric Coefficient of Variation 134.1 |
| Part A Cohort 5: M9241 16.8 mcg/kg + Avelumab 800 mg | Part A: Maximum Observed Serum Concentration (Cmax) of M9241 | Cycle 4 Day 1 | NA ng/mL | — |
Secondary
Part A: Minimum Observed Serum Concentration (Cmin) of Avelumab
Cmin is minimum observed serum concentration obtained directly from the concentration versus time curve.
Time frame: PrD, 1, 4, 8 hours PD on Day 1, 22 of cycle 1 & 2; PrD, 1 hour PD on Day 8, 15 of cycle 1 & Day 8, 15, 22 of cycle 2; PrD, 1 hour PD on Day 1 cycle 3 & Day 1, 15 of cycle 4; PrD on Day 1 of cycle 7, 10,13,16,19,22,25, & 28 (Each cycle: 28 days)
Population: Pharmacokinetic analysis set included all participants who completed at least 1 administration of avelumab and/or M9241, and who provided at least 1 sample with a measurable concentration of avelumab or M9241. Here, Overall Number of participants analyzed, signifies those participants who were evaluable for this outcome measure and Number analyzed signifies those participants who were evaluable at the specified time point.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kg | Part A: Minimum Observed Serum Concentration (Cmin) of Avelumab | Cycle 1 Day 15 | 11.3 mcg/mL | Geometric Coefficient of Variation 90.4 |
| Part A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kg | Part A: Minimum Observed Serum Concentration (Cmin) of Avelumab | Cycle 2 Day 1 | 20.5 mcg/mL | Geometric Coefficient of Variation 37.6 |
| Part A Cohort 2: M9241 8 mcg/kg + Avelumab 10 mg/kg | Part A: Minimum Observed Serum Concentration (Cmin) of Avelumab | Cycle 1 Day 15 | 14.5 mcg/mL | Geometric Coefficient of Variation 37.2 |
| Part A Cohort 2: M9241 8 mcg/kg + Avelumab 10 mg/kg | Part A: Minimum Observed Serum Concentration (Cmin) of Avelumab | Cycle 2 Day 1 | 24.0 mcg/mL | Geometric Coefficient of Variation 79.9 |
| Part A Cohort 3: M9241 12 mcg/kg + Avelumab 10 mg/kg | Part A: Minimum Observed Serum Concentration (Cmin) of Avelumab | Cycle 2 Day 1 | 14.4 mcg/mL | Geometric Coefficient of Variation 91.9 |
| Part A Cohort 3: M9241 12 mcg/kg + Avelumab 10 mg/kg | Part A: Minimum Observed Serum Concentration (Cmin) of Avelumab | Cycle 1 Day 15 | 14.0 mcg/mL | Geometric Coefficient of Variation 70.3 |
| Part A Cohort 4: M9241 16.8 mcg/kg +Avelumab 10 mg/kg | Part A: Minimum Observed Serum Concentration (Cmin) of Avelumab | Cycle 1 Day 15 | 9.28 mcg/mL | Geometric Coefficient of Variation 51.8 |
| Part A Cohort 4: M9241 16.8 mcg/kg +Avelumab 10 mg/kg | Part A: Minimum Observed Serum Concentration (Cmin) of Avelumab | Cycle 2 Day 1 | 13.1 mcg/mL | Geometric Coefficient of Variation 24.4 |
| Part A Cohort 5: M9241 16.8 mcg/kg + Avelumab 800 mg | Part A: Minimum Observed Serum Concentration (Cmin) of Avelumab | Cycle 1 Day 22 | 74.1 mcg/mL | Geometric Coefficient of Variation 62 |
| Part A Cohort 5: M9241 16.8 mcg/kg + Avelumab 800 mg | Part A: Minimum Observed Serum Concentration (Cmin) of Avelumab | Cycle 2 Day 1 | 59.3 mcg/mL | Geometric Coefficient of Variation 122.5 |
| Part A Cohort 5: M9241 16.8 mcg/kg + Avelumab 800 mg | Part A: Minimum Observed Serum Concentration (Cmin) of Avelumab | Cycle 4 Day 1 | NA mcg/mL | — |
| Unknown | Part A: Minimum Observed Serum Concentration (Cmin) of Avelumab | Cycle 16 Day 1 | — mcg/mL | — |
| Unknown | Part A: Minimum Observed Serum Concentration (Cmin) of Avelumab | Cycle 19 Day 1 | — mcg/mL | — |
| Unknown | Part A: Minimum Observed Serum Concentration (Cmin) of Avelumab | Cycle 28 Day 1 | — mcg/mL | — |
| Unknown | Part A: Minimum Observed Serum Concentration (Cmin) of Avelumab | Cycle 25 Day 1 | — mcg/mL | — |
| Unknown | Part A: Minimum Observed Serum Concentration (Cmin) of Avelumab | Cycle 22 Day 1 | — mcg/mL | — |
| Unknown | Part A: Minimum Observed Serum Concentration (Cmin) of Avelumab | Cycle 1 Day 1 | — mcg/mL | — |
| Unknown | Part A: Minimum Observed Serum Concentration (Cmin) of Avelumab | Cycle 1 Day 8 | — mcg/mL | — |
| Unknown | Part A: Minimum Observed Serum Concentration (Cmin) of Avelumab | Cycle 2 Day 8 | — mcg/mL | — |
| Unknown | Part A: Minimum Observed Serum Concentration (Cmin) of Avelumab | Cycle 2 Day 15 | — mcg/mL | — |
| Unknown | Part A: Minimum Observed Serum Concentration (Cmin) of Avelumab | Cycle 2 Day 22 | — mcg/mL | — |
| Unknown | Part A: Minimum Observed Serum Concentration (Cmin) of Avelumab | Cycle 3 Day 1 | — mcg/mL | — |
| Unknown | Part A: Minimum Observed Serum Concentration (Cmin) of Avelumab | Cycle 4 Day 15 | — mcg/mL | — |
| Unknown | Part A: Minimum Observed Serum Concentration (Cmin) of Avelumab | Cycle 7 Day 1 | — mcg/mL | — |
| Unknown | Part A: Minimum Observed Serum Concentration (Cmin) of Avelumab | Cycle 10 Day 1 | — mcg/mL | — |
| Unknown | Part A: Minimum Observed Serum Concentration (Cmin) of Avelumab | Cycle 13 Day 1 | — mcg/mL | — |
Secondary
Part A: Minimum Observed Serum Concentration (Cmin) of M9241
Cmin is minimum observed serum concentration obtained directly from the concentration versus time curve.
Time frame: PrD, 1, 4, 8 hours PD on Day 1 of cycle 1 and Day 1 of cycle 2; PrD on Day 15 of cycle 1 and cycle 2; PrD, 1 hour PD on Day 1 of cycle 3 and cycle 4; PrD on Day 1 Cycle 7, 10, 13, 16, 19, 22, 25, and 28 (Each cycle: 28 days)
Population: Pharmacokinetic analysis set included all participants who completed at least 1 administration of avelumab and/or M9241, and who provided at least 1 sample with a measurable concentration of avelumab or M9241. Here, Overall Number of participants analyzed, signifies those participants who were evaluable for this outcome measure and Number analyzed signifies those participants who were evaluable at the specified time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kg | Part A: Minimum Observed Serum Concentration (Cmin) of M9241 | Cycle 2 Day 1 | 0.0 ng/mL | Standard Deviation 0 |
| Part A Cohort 2: M9241 8 mcg/kg + Avelumab 10 mg/kg | Part A: Minimum Observed Serum Concentration (Cmin) of M9241 | Cycle 2 Day 1 | 0.0 ng/mL | Standard Deviation 0 |
| Part A Cohort 3: M9241 12 mcg/kg + Avelumab 10 mg/kg | Part A: Minimum Observed Serum Concentration (Cmin) of M9241 | Cycle 2 Day 1 | 0.0 ng/mL | Standard Deviation 0 |
| Part A Cohort 4: M9241 16.8 mcg/kg +Avelumab 10 mg/kg | Part A: Minimum Observed Serum Concentration (Cmin) of M9241 | Cycle 2 Day 1 | 0.0 ng/mL | Standard Deviation 0 |
| Part A Cohort 5: M9241 16.8 mcg/kg + Avelumab 800 mg | Part A: Minimum Observed Serum Concentration (Cmin) of M9241 | Cycle 2 Day 1 | 0.0 ng/mL | Standard Deviation 0 |
| Unknown | Part A: Minimum Observed Serum Concentration (Cmin) of M9241 | Cycle 3 Day 1 | — ng/mL | — |
| Unknown | Part A: Minimum Observed Serum Concentration (Cmin) of M9241 | Cycle 4 Day 1 | — ng/mL | — |
| Unknown | Part A: Minimum Observed Serum Concentration (Cmin) of M9241 | Cycle 7 Day 1 | — ng/mL | — |
| Unknown | Part A: Minimum Observed Serum Concentration (Cmin) of M9241 | Cycle 10 Day 1 | — ng/mL | — |
| Unknown | Part A: Minimum Observed Serum Concentration (Cmin) of M9241 | Cycle 25 Day 1 | — ng/mL | — |
| Unknown | Part A: Minimum Observed Serum Concentration (Cmin) of M9241 | Cycle 16 Day 1 | — ng/mL | — |
| Unknown | Part A: Minimum Observed Serum Concentration (Cmin) of M9241 | Cycle 19 Day 1 | — ng/mL | — |
| Unknown | Part A: Minimum Observed Serum Concentration (Cmin) of M9241 | Cycle 28 Day 1 | — ng/mL | — |
| Unknown | Part A: Minimum Observed Serum Concentration (Cmin) of M9241 | Cycle 13 Day 1 | — ng/mL | — |
| Unknown | Part A: Minimum Observed Serum Concentration (Cmin) of M9241 | Cycle 22 Day 1 | — ng/mL | — |
| Unknown | Part A: Minimum Observed Serum Concentration (Cmin) of M9241 | Cycle 1 Day 1 | — ng/mL | — |
| Unknown | Part A: Minimum Observed Serum Concentration (Cmin) of M9241 | Cycle 1 Day 15 | — ng/mL | — |
| Unknown | Part A: Minimum Observed Serum Concentration (Cmin) of M9241 | Cycle 2 Day 15 | — ng/mL | — |
Secondary
Part A: Number of Participants With At Least One Positive Anti-drug Antibodies (ADA) for Avelumab and M9241
ADA category of each participant was classified as pre-existing immunoreactivity (positive ADA response at baseline (prior to treatment), treatment-boosted (positive response at baseline with at least one post baseline titer at \>=8-fold baseline titer), or treatment-emergent (TE \[any positive post baseline assay response when baseline results were negative or missing or not reported\]). TE ADA responses were further classified as persistent (treatment-emergent positive ADA response detected in at least 2 consecutive post baseline samples separated by at least a 16-week post baseline period \[based on nominal sampling time\], with no ADA-negative samples in-between or positive response at last ADA sampling time point) and transient (not persistent/indeterminate, regardless of any missing samples).
Time frame: First dose of study drug up to 1311 days
Population: Immunogenicity analysis set included all participants who received at least 1 complete dose (at least 90% of planned dose) of any study treatment \& at least 1 valid ADA result for avelumab or NHS-IL12.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kg | Part A: Number of Participants With At Least One Positive Anti-drug Antibodies (ADA) for Avelumab and M9241 | Avelumab: Treatment-Emergent Persistent Positive | 0 Participants |
| Part A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kg | Part A: Number of Participants With At Least One Positive Anti-drug Antibodies (ADA) for Avelumab and M9241 | M9241: ADA Treatment boosted | 0 Participants |
| Part A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kg | Part A: Number of Participants With At Least One Positive Anti-drug Antibodies (ADA) for Avelumab and M9241 | M9241: ADA pre-existing | 0 Participants |
| Part A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kg | Part A: Number of Participants With At Least One Positive Anti-drug Antibodies (ADA) for Avelumab and M9241 | Avelumab: Treatment-Emergent Transient positive | 0 Participants |
| Part A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kg | Part A: Number of Participants With At Least One Positive Anti-drug Antibodies (ADA) for Avelumab and M9241 | Avelumab: ADA Treatment boosted | 0 Participants |
| Part A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kg | Part A: Number of Participants With At Least One Positive Anti-drug Antibodies (ADA) for Avelumab and M9241 | M9241: Treatment-Emergent Persistent Positive | 0 Participants |
| Part A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kg | Part A: Number of Participants With At Least One Positive Anti-drug Antibodies (ADA) for Avelumab and M9241 | M9241: Treatment-Emergent Transient Positive | 0 Participants |
| Part A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kg | Part A: Number of Participants With At Least One Positive Anti-drug Antibodies (ADA) for Avelumab and M9241 | Avelumab: ADA pre-existing | 0 Participants |
| Part A Cohort 2: M9241 8 mcg/kg + Avelumab 10 mg/kg | Part A: Number of Participants With At Least One Positive Anti-drug Antibodies (ADA) for Avelumab and M9241 | M9241: ADA pre-existing | 0 Participants |
| Part A Cohort 2: M9241 8 mcg/kg + Avelumab 10 mg/kg | Part A: Number of Participants With At Least One Positive Anti-drug Antibodies (ADA) for Avelumab and M9241 | M9241: Treatment-Emergent Transient Positive | 0 Participants |
| Part A Cohort 2: M9241 8 mcg/kg + Avelumab 10 mg/kg | Part A: Number of Participants With At Least One Positive Anti-drug Antibodies (ADA) for Avelumab and M9241 | Avelumab: ADA Treatment boosted | 0 Participants |
| Part A Cohort 2: M9241 8 mcg/kg + Avelumab 10 mg/kg | Part A: Number of Participants With At Least One Positive Anti-drug Antibodies (ADA) for Avelumab and M9241 | Avelumab: ADA pre-existing | 0 Participants |
| Part A Cohort 2: M9241 8 mcg/kg + Avelumab 10 mg/kg | Part A: Number of Participants With At Least One Positive Anti-drug Antibodies (ADA) for Avelumab and M9241 | M9241: Treatment-Emergent Persistent Positive | 0 Participants |
| Part A Cohort 2: M9241 8 mcg/kg + Avelumab 10 mg/kg | Part A: Number of Participants With At Least One Positive Anti-drug Antibodies (ADA) for Avelumab and M9241 | Avelumab: Treatment-Emergent Transient positive | 0 Participants |
| Part A Cohort 2: M9241 8 mcg/kg + Avelumab 10 mg/kg | Part A: Number of Participants With At Least One Positive Anti-drug Antibodies (ADA) for Avelumab and M9241 | M9241: ADA Treatment boosted | 0 Participants |
| Part A Cohort 2: M9241 8 mcg/kg + Avelumab 10 mg/kg | Part A: Number of Participants With At Least One Positive Anti-drug Antibodies (ADA) for Avelumab and M9241 | Avelumab: Treatment-Emergent Persistent Positive | 1 Participants |
| Part A Cohort 3: M9241 12 mcg/kg + Avelumab 10 mg/kg | Part A: Number of Participants With At Least One Positive Anti-drug Antibodies (ADA) for Avelumab and M9241 | Avelumab: ADA Treatment boosted | 0 Participants |
| Part A Cohort 3: M9241 12 mcg/kg + Avelumab 10 mg/kg | Part A: Number of Participants With At Least One Positive Anti-drug Antibodies (ADA) for Avelumab and M9241 | M9241: ADA Treatment boosted | 0 Participants |
| Part A Cohort 3: M9241 12 mcg/kg + Avelumab 10 mg/kg | Part A: Number of Participants With At Least One Positive Anti-drug Antibodies (ADA) for Avelumab and M9241 | M9241: ADA pre-existing | 0 Participants |
| Part A Cohort 3: M9241 12 mcg/kg + Avelumab 10 mg/kg | Part A: Number of Participants With At Least One Positive Anti-drug Antibodies (ADA) for Avelumab and M9241 | Avelumab: Treatment-Emergent Persistent Positive | 1 Participants |
| Part A Cohort 3: M9241 12 mcg/kg + Avelumab 10 mg/kg | Part A: Number of Participants With At Least One Positive Anti-drug Antibodies (ADA) for Avelumab and M9241 | M9241: Treatment-Emergent Persistent Positive | 0 Participants |
| Part A Cohort 3: M9241 12 mcg/kg + Avelumab 10 mg/kg | Part A: Number of Participants With At Least One Positive Anti-drug Antibodies (ADA) for Avelumab and M9241 | M9241: Treatment-Emergent Transient Positive | 0 Participants |
| Part A Cohort 3: M9241 12 mcg/kg + Avelumab 10 mg/kg | Part A: Number of Participants With At Least One Positive Anti-drug Antibodies (ADA) for Avelumab and M9241 | Avelumab: ADA pre-existing | 0 Participants |
| Part A Cohort 3: M9241 12 mcg/kg + Avelumab 10 mg/kg | Part A: Number of Participants With At Least One Positive Anti-drug Antibodies (ADA) for Avelumab and M9241 | Avelumab: Treatment-Emergent Transient positive | 1 Participants |
| Part A Cohort 4: M9241 16.8 mcg/kg +Avelumab 10 mg/kg | Part A: Number of Participants With At Least One Positive Anti-drug Antibodies (ADA) for Avelumab and M9241 | Avelumab: Treatment-Emergent Persistent Positive | 0 Participants |
| Part A Cohort 4: M9241 16.8 mcg/kg +Avelumab 10 mg/kg | Part A: Number of Participants With At Least One Positive Anti-drug Antibodies (ADA) for Avelumab and M9241 | M9241: Treatment-Emergent Transient Positive | 0 Participants |
| Part A Cohort 4: M9241 16.8 mcg/kg +Avelumab 10 mg/kg | Part A: Number of Participants With At Least One Positive Anti-drug Antibodies (ADA) for Avelumab and M9241 | Avelumab: ADA pre-existing | 0 Participants |
| Part A Cohort 4: M9241 16.8 mcg/kg +Avelumab 10 mg/kg | Part A: Number of Participants With At Least One Positive Anti-drug Antibodies (ADA) for Avelumab and M9241 | Avelumab: ADA Treatment boosted | 0 Participants |
| Part A Cohort 4: M9241 16.8 mcg/kg +Avelumab 10 mg/kg | Part A: Number of Participants With At Least One Positive Anti-drug Antibodies (ADA) for Avelumab and M9241 | Avelumab: Treatment-Emergent Transient positive | 1 Participants |
| Part A Cohort 4: M9241 16.8 mcg/kg +Avelumab 10 mg/kg | Part A: Number of Participants With At Least One Positive Anti-drug Antibodies (ADA) for Avelumab and M9241 | M9241: ADA pre-existing | 0 Participants |
| Part A Cohort 4: M9241 16.8 mcg/kg +Avelumab 10 mg/kg | Part A: Number of Participants With At Least One Positive Anti-drug Antibodies (ADA) for Avelumab and M9241 | M9241: ADA Treatment boosted | 0 Participants |
| Part A Cohort 4: M9241 16.8 mcg/kg +Avelumab 10 mg/kg | Part A: Number of Participants With At Least One Positive Anti-drug Antibodies (ADA) for Avelumab and M9241 | M9241: Treatment-Emergent Persistent Positive | 0 Participants |
| Part A Cohort 5: M9241 16.8 mcg/kg + Avelumab 800 mg | Part A: Number of Participants With At Least One Positive Anti-drug Antibodies (ADA) for Avelumab and M9241 | M9241: ADA pre-existing | 0 Participants |
| Part A Cohort 5: M9241 16.8 mcg/kg + Avelumab 800 mg | Part A: Number of Participants With At Least One Positive Anti-drug Antibodies (ADA) for Avelumab and M9241 | Avelumab: Treatment-Emergent Persistent Positive | 1 Participants |
| Part A Cohort 5: M9241 16.8 mcg/kg + Avelumab 800 mg | Part A: Number of Participants With At Least One Positive Anti-drug Antibodies (ADA) for Avelumab and M9241 | M9241: Treatment-Emergent Transient Positive | 0 Participants |
| Part A Cohort 5: M9241 16.8 mcg/kg + Avelumab 800 mg | Part A: Number of Participants With At Least One Positive Anti-drug Antibodies (ADA) for Avelumab and M9241 | Avelumab: Treatment-Emergent Transient positive | 0 Participants |
| Part A Cohort 5: M9241 16.8 mcg/kg + Avelumab 800 mg | Part A: Number of Participants With At Least One Positive Anti-drug Antibodies (ADA) for Avelumab and M9241 | Avelumab: ADA Treatment boosted | 0 Participants |
| Part A Cohort 5: M9241 16.8 mcg/kg + Avelumab 800 mg | Part A: Number of Participants With At Least One Positive Anti-drug Antibodies (ADA) for Avelumab and M9241 | Avelumab: ADA pre-existing | 1 Participants |
| Part A Cohort 5: M9241 16.8 mcg/kg + Avelumab 800 mg | Part A: Number of Participants With At Least One Positive Anti-drug Antibodies (ADA) for Avelumab and M9241 | M9241: Treatment-Emergent Persistent Positive | 1 Participants |
| Part A Cohort 5: M9241 16.8 mcg/kg + Avelumab 800 mg | Part A: Number of Participants With At Least One Positive Anti-drug Antibodies (ADA) for Avelumab and M9241 | M9241: ADA Treatment boosted | 0 Participants |
Secondary
Part A: Number of Participants With Confirmed Best Overall Response (BOR) According to Response Evaluation Criteria in Solid Tumors Version 1.1
BOR is defined as best response of any of confirmed complete response, confirmed partial response, stable disease and progressive disease recorded from date of randomization until disease progression or recurrence. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30 percent (%) reduction from baseline in the sum of the longest diameter (SLD) of all lesions. Stable disease (SD)= Neither sufficient increase to qualify for progression of disease (PD) nor sufficient shrinkage to qualify for PR. PD: At least a 20 % increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions. Non-CR/non-PD (for participants with non-measurable disease at baseline) = at least one Non-CR/non-PD assessment (or better) \>= 6 weeks after first study treatment administration and before progression and Not Evaluable: all other cases. BOR assessments were assessed by investigators.
Time frame: First dose of study drug up to 1311 days
Population: Full analysis set included all participants who received at least 1 dose of any study treatment.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kg | Part A: Number of Participants With Confirmed Best Overall Response (BOR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 | Partial Response (PR) | 0 Participants |
| Part A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kg | Part A: Number of Participants With Confirmed Best Overall Response (BOR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 | Not Evaluable | 1 Participants |
| Part A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kg | Part A: Number of Participants With Confirmed Best Overall Response (BOR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 | Stable Disease (SD) | 2 Participants |
| Part A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kg | Part A: Number of Participants With Confirmed Best Overall Response (BOR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 | Non CR/Non PD | 0 Participants |
| Part A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kg | Part A: Number of Participants With Confirmed Best Overall Response (BOR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 | Progressive Disease (PD) | 6 Participants |
| Part A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kg | Part A: Number of Participants With Confirmed Best Overall Response (BOR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 | Complete Response (CR) | 0 Participants |
| Part A Cohort 2: M9241 8 mcg/kg + Avelumab 10 mg/kg | Part A: Number of Participants With Confirmed Best Overall Response (BOR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 | Stable Disease (SD) | 2 Participants |
| Part A Cohort 2: M9241 8 mcg/kg + Avelumab 10 mg/kg | Part A: Number of Participants With Confirmed Best Overall Response (BOR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 | Not Evaluable | 1 Participants |
| Part A Cohort 2: M9241 8 mcg/kg + Avelumab 10 mg/kg | Part A: Number of Participants With Confirmed Best Overall Response (BOR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 | Partial Response (PR) | 0 Participants |
| Part A Cohort 2: M9241 8 mcg/kg + Avelumab 10 mg/kg | Part A: Number of Participants With Confirmed Best Overall Response (BOR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 | Complete Response (CR) | 1 Participants |
| Part A Cohort 2: M9241 8 mcg/kg + Avelumab 10 mg/kg | Part A: Number of Participants With Confirmed Best Overall Response (BOR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 | Progressive Disease (PD) | 3 Participants |
| Part A Cohort 2: M9241 8 mcg/kg + Avelumab 10 mg/kg | Part A: Number of Participants With Confirmed Best Overall Response (BOR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 | Non CR/Non PD | 0 Participants |
| Part A Cohort 3: M9241 12 mcg/kg + Avelumab 10 mg/kg | Part A: Number of Participants With Confirmed Best Overall Response (BOR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 | Partial Response (PR) | 0 Participants |
| Part A Cohort 3: M9241 12 mcg/kg + Avelumab 10 mg/kg | Part A: Number of Participants With Confirmed Best Overall Response (BOR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 | Stable Disease (SD) | 2 Participants |
| Part A Cohort 3: M9241 12 mcg/kg + Avelumab 10 mg/kg | Part A: Number of Participants With Confirmed Best Overall Response (BOR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 | Complete Response (CR) | 0 Participants |
| Part A Cohort 3: M9241 12 mcg/kg + Avelumab 10 mg/kg | Part A: Number of Participants With Confirmed Best Overall Response (BOR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 | Non CR/Non PD | 0 Participants |
| Part A Cohort 3: M9241 12 mcg/kg + Avelumab 10 mg/kg | Part A: Number of Participants With Confirmed Best Overall Response (BOR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 | Progressive Disease (PD) | 4 Participants |
| Part A Cohort 3: M9241 12 mcg/kg + Avelumab 10 mg/kg | Part A: Number of Participants With Confirmed Best Overall Response (BOR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 | Not Evaluable | 1 Participants |
| Part A Cohort 4: M9241 16.8 mcg/kg +Avelumab 10 mg/kg | Part A: Number of Participants With Confirmed Best Overall Response (BOR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 | Non CR/Non PD | 0 Participants |
| Part A Cohort 4: M9241 16.8 mcg/kg +Avelumab 10 mg/kg | Part A: Number of Participants With Confirmed Best Overall Response (BOR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 | Complete Response (CR) | 1 Participants |
| Part A Cohort 4: M9241 16.8 mcg/kg +Avelumab 10 mg/kg | Part A: Number of Participants With Confirmed Best Overall Response (BOR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 | Stable Disease (SD) | 1 Participants |
| Part A Cohort 4: M9241 16.8 mcg/kg +Avelumab 10 mg/kg | Part A: Number of Participants With Confirmed Best Overall Response (BOR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 | Progressive Disease (PD) | 2 Participants |
| Part A Cohort 4: M9241 16.8 mcg/kg +Avelumab 10 mg/kg | Part A: Number of Participants With Confirmed Best Overall Response (BOR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 | Not Evaluable | 2 Participants |
| Part A Cohort 4: M9241 16.8 mcg/kg +Avelumab 10 mg/kg | Part A: Number of Participants With Confirmed Best Overall Response (BOR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 | Partial Response (PR) | 0 Participants |
| Part A Cohort 5: M9241 16.8 mcg/kg + Avelumab 800 mg | Part A: Number of Participants With Confirmed Best Overall Response (BOR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 | Not Evaluable | 0 Participants |
| Part A Cohort 5: M9241 16.8 mcg/kg + Avelumab 800 mg | Part A: Number of Participants With Confirmed Best Overall Response (BOR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 | Complete Response (CR) | 0 Participants |
| Part A Cohort 5: M9241 16.8 mcg/kg + Avelumab 800 mg | Part A: Number of Participants With Confirmed Best Overall Response (BOR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 | Partial Response (PR) | 0 Participants |
| Part A Cohort 5: M9241 16.8 mcg/kg + Avelumab 800 mg | Part A: Number of Participants With Confirmed Best Overall Response (BOR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 | Stable Disease (SD) | 2 Participants |
| Part A Cohort 5: M9241 16.8 mcg/kg + Avelumab 800 mg | Part A: Number of Participants With Confirmed Best Overall Response (BOR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 | Progressive Disease (PD) | 5 Participants |
| Part A Cohort 5: M9241 16.8 mcg/kg + Avelumab 800 mg | Part A: Number of Participants With Confirmed Best Overall Response (BOR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 | Non CR/Non PD | 0 Participants |
Secondary
Part A: Terminal Elimination Rate Constant (Lambdaz) of Avelumab
Lambda(z) was determined from the terminal slope of the log-transformed serum concentration curve using linear regression method.
Time frame: PrD, 1, 4, 8 hours PD on Day 1, 22 of cycle 1 & 2; PrD, 1 hour PD on Day 8, 15 of cycle 1 & Day 8, 15, 22 of cycle 2; PrD, 1 hour PD on Day 1 cycle 3 & Day 1, 15 of cycle 4; PrD on Day 1 of cycle 7, 10,13,16,19,22,25, & 28 (Each cycle: 28 days)
Population: Pharmacokinetic analysis set included all participants who completed at least 1 administration of avelumab and/or M9241, and who provided at least 1 sample with a measurable concentration of avelumab or M9241. Here, Overall Number of participants analyzed, signifies those participants who were evaluable for this outcome measure and Number analyzed signifies those participants who were evaluable at the specified time point.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kg | Part A: Terminal Elimination Rate Constant (Lambdaz) of Avelumab | Cycle 1 Day 1 | 0.00847 One per hour (1/hour) | Geometric Coefficient of Variation 29.6 |
| Part A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kg | Part A: Terminal Elimination Rate Constant (Lambdaz) of Avelumab | Cycle 2 Day 1 | 0.00659 One per hour (1/hour) | Geometric Coefficient of Variation 15.7 |
| Part A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kg | Part A: Terminal Elimination Rate Constant (Lambdaz) of Avelumab | Cycle 1 Day 15 | 0.00780 One per hour (1/hour) | Geometric Coefficient of Variation 31.6 |
| Part A Cohort 2: M9241 8 mcg/kg + Avelumab 10 mg/kg | Part A: Terminal Elimination Rate Constant (Lambdaz) of Avelumab | Cycle 1 Day 15 | 0.00814 One per hour (1/hour) | Geometric Coefficient of Variation 15.7 |
| Part A Cohort 2: M9241 8 mcg/kg + Avelumab 10 mg/kg | Part A: Terminal Elimination Rate Constant (Lambdaz) of Avelumab | Cycle 1 Day 1 | 0.00729 One per hour (1/hour) | Geometric Coefficient of Variation 48.5 |
| Part A Cohort 2: M9241 8 mcg/kg + Avelumab 10 mg/kg | Part A: Terminal Elimination Rate Constant (Lambdaz) of Avelumab | Cycle 2 Day 1 | 0.00714 One per hour (1/hour) | Geometric Coefficient of Variation 39.8 |
| Part A Cohort 3: M9241 12 mcg/kg + Avelumab 10 mg/kg | Part A: Terminal Elimination Rate Constant (Lambdaz) of Avelumab | Cycle 1 Day 15 | 0.00780 One per hour (1/hour) | Geometric Coefficient of Variation 31.4 |
| Part A Cohort 3: M9241 12 mcg/kg + Avelumab 10 mg/kg | Part A: Terminal Elimination Rate Constant (Lambdaz) of Avelumab | Cycle 1 Day 1 | 0.00756 One per hour (1/hour) | Geometric Coefficient of Variation 20.6 |
| Part A Cohort 3: M9241 12 mcg/kg + Avelumab 10 mg/kg | Part A: Terminal Elimination Rate Constant (Lambdaz) of Avelumab | Cycle 2 Day 1 | 0.00868 One per hour (1/hour) | Geometric Coefficient of Variation 19.2 |
| Part A Cohort 4: M9241 16.8 mcg/kg +Avelumab 10 mg/kg | Part A: Terminal Elimination Rate Constant (Lambdaz) of Avelumab | Cycle 1 Day 1 | 0.00790 One per hour (1/hour) | Geometric Coefficient of Variation 14.4 |
| Part A Cohort 4: M9241 16.8 mcg/kg +Avelumab 10 mg/kg | Part A: Terminal Elimination Rate Constant (Lambdaz) of Avelumab | Cycle 2 Day 1 | 0.00830 One per hour (1/hour) | Geometric Coefficient of Variation 16.4 |
| Part A Cohort 4: M9241 16.8 mcg/kg +Avelumab 10 mg/kg | Part A: Terminal Elimination Rate Constant (Lambdaz) of Avelumab | Cycle 1 Day 15 | 0.00803 One per hour (1/hour) | Geometric Coefficient of Variation 17.1 |
| Part A Cohort 5: M9241 16.8 mcg/kg + Avelumab 800 mg | Part A: Terminal Elimination Rate Constant (Lambdaz) of Avelumab | Cycle 1 Day 22 | 0.00620 One per hour (1/hour) | Geometric Coefficient of Variation 34.3 |
| Part A Cohort 5: M9241 16.8 mcg/kg + Avelumab 800 mg | Part A: Terminal Elimination Rate Constant (Lambdaz) of Avelumab | Cycle 1 Day 1 | 0.00822 One per hour (1/hour) | Geometric Coefficient of Variation 37.1 |
| Part A Cohort 5: M9241 16.8 mcg/kg + Avelumab 800 mg | Part A: Terminal Elimination Rate Constant (Lambdaz) of Avelumab | Cycle 2 Day 1 | 0.00793 One per hour (1/hour) | Geometric Coefficient of Variation 35.9 |
Secondary
Part A: Terminal Elimination Rate Constant (Lambdaz) of M9241
Lambda(z) was determined from the terminal slope of the log-transformed serum concentration curve using linear regression method.
Time frame: PrD, 1, 4, 8 hours PD on Day 1 of cycle 1 and Day 1 of cycle 2; PrD on Day 15 of cycle 1 and cycle 2; PrD, 1 hour PD on Day 1 of cycle 3 and cycle 4; PrD on Day 1 Cycle 7, 10, 13, 16, 19, 22, 25, and 28 (Each cycle: 28 days)
Population: Pharmacokinetic analysis set included participants who completed at least 1 administration of avelumab and/or M9241 and provided at least 1 sample with a measurable concentration. Here, Overall Number of participants analyzed, signifies participants evaluable for this outcome measure and Number analyzed signifies participants evaluable at the specified time point. None of the participants were analyzed in Part A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kg arm at specified timepoints.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A Cohort 2: M9241 8 mcg/kg + Avelumab 10 mg/kg | Part A: Terminal Elimination Rate Constant (Lambdaz) of M9241 | Cycle 2 Day 1 | NA One per hour (1/hour) | — |
| Part A Cohort 2: M9241 8 mcg/kg + Avelumab 10 mg/kg | Part A: Terminal Elimination Rate Constant (Lambdaz) of M9241 | Cycle 1 Day 1 | NA One per hour (1/hour) | — |
| Part A Cohort 3: M9241 12 mcg/kg + Avelumab 10 mg/kg | Part A: Terminal Elimination Rate Constant (Lambdaz) of M9241 | Cycle 1 Day 1 | NA One per hour (1/hour) | — |
| Part A Cohort 4: M9241 16.8 mcg/kg +Avelumab 10 mg/kg | Part A: Terminal Elimination Rate Constant (Lambdaz) of M9241 | Cycle 1 Day 1 | NA One per hour (1/hour) | — |
| Part A Cohort 4: M9241 16.8 mcg/kg +Avelumab 10 mg/kg | Part A: Terminal Elimination Rate Constant (Lambdaz) of M9241 | Cycle 2 Day 1 | NA One per hour (1/hour) | — |
| Part A Cohort 5: M9241 16.8 mcg/kg + Avelumab 800 mg | Part A: Terminal Elimination Rate Constant (Lambdaz) of M9241 | Cycle 1 Day 1 | 0.00451 One per hour (1/hour) | Geometric Coefficient of Variation 12.5 |
| Part A Cohort 5: M9241 16.8 mcg/kg + Avelumab 800 mg | Part A: Terminal Elimination Rate Constant (Lambdaz) of M9241 | Cycle 2 Day 1 | 0.00835 One per hour (1/hour) | Geometric Coefficient of Variation 14 |
| Part A Cohort 5: M9241 16.8 mcg/kg + Avelumab 800 mg | Part A: Terminal Elimination Rate Constant (Lambdaz) of M9241 | Cycle 4 Day 1 | NA One per hour (1/hour) | — |
Secondary
Part A: Time to Reach Maximum Observed Concentration (Tmax) of Avelumab
Tmax is time to reach maximum observed serum concentration obtained directly from the concentration versus time curve.
Time frame: PrD, 1, 4, 8 hours PD on Day 1, 22 of cycle 1 & 2; PrD, 1 hour PD on Day 8, 15 of cycle 1 & Day 8, 15, 22 of cycle 2; PrD, 1 hour PD on Day 1 cycle 3 & Day 1, 15 of cycle 4; PrD on Day 1 of cycle 7, 10,13,16,19,22,25, & 28 (Each cycle: 28 days)
Population: Pharmacokinetic analysis set included all participants who completed at least 1 administration of avelumab and/or M9241, and who provided at least 1 sample with a measurable concentration of avelumab or M9241. Here, Overall Number of participants analyzed, signifies those participants who were evaluable for this outcome measure and Number analyzed signifies those participants who were evaluable at the specified time point.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kg | Part A: Time to Reach Maximum Observed Concentration (Tmax) of Avelumab | Cycle 2 Day 1 | 1.58 hours |
| Part A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kg | Part A: Time to Reach Maximum Observed Concentration (Tmax) of Avelumab | Cycle 1 Day 15 | 5.04 hours |
| Part A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kg | Part A: Time to Reach Maximum Observed Concentration (Tmax) of Avelumab | Cycle 1 Day 1 | 4.00 hours |
| Part A Cohort 2: M9241 8 mcg/kg + Avelumab 10 mg/kg | Part A: Time to Reach Maximum Observed Concentration (Tmax) of Avelumab | Cycle 2 Day 1 | 1.17 hours |
| Part A Cohort 2: M9241 8 mcg/kg + Avelumab 10 mg/kg | Part A: Time to Reach Maximum Observed Concentration (Tmax) of Avelumab | Cycle 1 Day 1 | 1.05 hours |
| Part A Cohort 2: M9241 8 mcg/kg + Avelumab 10 mg/kg | Part A: Time to Reach Maximum Observed Concentration (Tmax) of Avelumab | Cycle 1 Day 15 | 1.13 hours |
| Part A Cohort 3: M9241 12 mcg/kg + Avelumab 10 mg/kg | Part A: Time to Reach Maximum Observed Concentration (Tmax) of Avelumab | Cycle 2 Day 1 | 23.07 hours |
| Part A Cohort 3: M9241 12 mcg/kg + Avelumab 10 mg/kg | Part A: Time to Reach Maximum Observed Concentration (Tmax) of Avelumab | Cycle 1 Day 15 | 4.00 hours |
| Part A Cohort 3: M9241 12 mcg/kg + Avelumab 10 mg/kg | Part A: Time to Reach Maximum Observed Concentration (Tmax) of Avelumab | Cycle 1 Day 1 | 3.90 hours |
| Part A Cohort 4: M9241 16.8 mcg/kg +Avelumab 10 mg/kg | Part A: Time to Reach Maximum Observed Concentration (Tmax) of Avelumab | Cycle 1 Day 15 | 4.09 hours |
| Part A Cohort 4: M9241 16.8 mcg/kg +Avelumab 10 mg/kg | Part A: Time to Reach Maximum Observed Concentration (Tmax) of Avelumab | Cycle 1 Day 1 | 2.58 hours |
| Part A Cohort 4: M9241 16.8 mcg/kg +Avelumab 10 mg/kg | Part A: Time to Reach Maximum Observed Concentration (Tmax) of Avelumab | Cycle 2 Day 1 | 2.00 hours |
| Part A Cohort 5: M9241 16.8 mcg/kg + Avelumab 800 mg | Part A: Time to Reach Maximum Observed Concentration (Tmax) of Avelumab | Cycle 1 Day 1 | 4.00 hours |
| Part A Cohort 5: M9241 16.8 mcg/kg + Avelumab 800 mg | Part A: Time to Reach Maximum Observed Concentration (Tmax) of Avelumab | Cycle 4 Day 1 | NA hours |
| Part A Cohort 5: M9241 16.8 mcg/kg + Avelumab 800 mg | Part A: Time to Reach Maximum Observed Concentration (Tmax) of Avelumab | Cycle 2 Day 1 | 4.00 hours |
| Part A Cohort 5: M9241 16.8 mcg/kg + Avelumab 800 mg | Part A: Time to Reach Maximum Observed Concentration (Tmax) of Avelumab | Cycle 1 Day 22 | 4.00 hours |
Secondary
Part A: Time to Reach Maximum Observed Concentration (Tmax) of M9241
Tmax is time to reach maximum observed serum concentration obtained directly from the concentration versus time curve.
Time frame: PrD, 1, 4, 8 hours PD on Day 1 of cycle 1 and Day 1 of cycle 2; PrD on Day 15 of cycle 1 and cycle 2; PrD, 1 hour PD on Day 1 of cycle 3 and cycle 4; PrD on Day 1 Cycle 7, 10, 13, 16, 19, 22, 25, and 28 (Each cycle: 28 days)
Population: Pharmacokinetic analysis set included all participants who completed at least 1 administration of avelumab and/or M9241, and who provided at least 1 sample with a measurable concentration of avelumab or M9241. Here, Overall Number of participants analyzed, signifies those participants who were evaluable for this outcome measure and Number analyzed signifies those participants who were evaluable at the specified time point.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kg | Part A: Time to Reach Maximum Observed Concentration (Tmax) of M9241 | Cycle 2 Day 1 | 34.28 hours |
| Part A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kg | Part A: Time to Reach Maximum Observed Concentration (Tmax) of M9241 | Cycle 1 Day 1 | 25.08 hours |
| Part A Cohort 2: M9241 8 mcg/kg + Avelumab 10 mg/kg | Part A: Time to Reach Maximum Observed Concentration (Tmax) of M9241 | Cycle 1 Day 1 | 25.17 hours |
| Part A Cohort 2: M9241 8 mcg/kg + Avelumab 10 mg/kg | Part A: Time to Reach Maximum Observed Concentration (Tmax) of M9241 | Cycle 2 Day 1 | 25.17 hours |
| Part A Cohort 3: M9241 12 mcg/kg + Avelumab 10 mg/kg | Part A: Time to Reach Maximum Observed Concentration (Tmax) of M9241 | Cycle 2 Day 1 | 25.08 hours |
| Part A Cohort 3: M9241 12 mcg/kg + Avelumab 10 mg/kg | Part A: Time to Reach Maximum Observed Concentration (Tmax) of M9241 | Cycle 1 Day 1 | 24.11 hours |
| Part A Cohort 4: M9241 16.8 mcg/kg +Avelumab 10 mg/kg | Part A: Time to Reach Maximum Observed Concentration (Tmax) of M9241 | Cycle 1 Day 1 | 36.17 hours |
| Part A Cohort 4: M9241 16.8 mcg/kg +Avelumab 10 mg/kg | Part A: Time to Reach Maximum Observed Concentration (Tmax) of M9241 | Cycle 2 Day 1 | 25.43 hours |
| Part A Cohort 5: M9241 16.8 mcg/kg + Avelumab 800 mg | Part A: Time to Reach Maximum Observed Concentration (Tmax) of M9241 | Cycle 4 Day 1 | NA hours |
| Part A Cohort 5: M9241 16.8 mcg/kg + Avelumab 800 mg | Part A: Time to Reach Maximum Observed Concentration (Tmax) of M9241 | Cycle 1 Day 1 | 25.08 hours |
| Part A Cohort 5: M9241 16.8 mcg/kg + Avelumab 800 mg | Part A: Time to Reach Maximum Observed Concentration (Tmax) of M9241 | Cycle 2 Day 1 | 25.50 hours |
Secondary
Part B: Concentration at the End of Infusion (Ceoi) of Avelumab
Ceoi is the observed serum drug concentration at the end of Intravenous (IV) infusion.
Time frame: Pre-dose, 1 hour post-dose on Day 1 and 15 of Cycle 1 and 2 (Each cycle: 28 days)
Population: Pharmacokinetic analysis set included all participants who completed at least 1 administration of avelumab and/or M9241, and who provided at least 1 sample with a measurable concentration of avelumab or M9241. Here, Number analyzed signifies those participants who were evaluable at the specified time point.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kg | Part B: Concentration at the End of Infusion (Ceoi) of Avelumab | Day 1 | 199 mcg/mL | Geometric Coefficient of Variation 22 |
| Part A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kg | Part B: Concentration at the End of Infusion (Ceoi) of Avelumab | Day 15 | 220 mcg/mL | Geometric Coefficient of Variation 37.9 |
| Part A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kg | Part B: Concentration at the End of Infusion (Ceoi) of Avelumab | Day 29 | 272 mcg/mL | Geometric Coefficient of Variation 59.6 |
| Part A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kg | Part B: Concentration at the End of Infusion (Ceoi) of Avelumab | Day 43 | 253 mcg/mL | Geometric Coefficient of Variation 40 |
Secondary
Part B: Duration of Response (DOR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) Criteria Assessed by Investigator
DOR according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) and as assessed by an Investigator was defined as the time from first documentation of objective response (Complete Response \[CR\] or Partial Response \[PR\]) to the date of first documentation of objective progression of disease (PD) or death due to any cause whichever occurs first. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the sum of the longest diameter (SLD) of all lesions. PD was defined as at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions. If a participant has not an event (PD or death), DOR was censored at the date of last adequate tumor assessment.
Time frame: Time from first dose of study treatment up to 443 days
Population: Data could not be calculated as none of the participants showed objective response.
Secondary
Part B: Maximum Observed Serum Concentration (Cmax) of M9241
Cmax is the maximum observed serum concentration obtained directly from the concentration versus time curve.
Time frame: Pre-dose, 1 hour post-dose on Day 1 and Day 29 of Cycle 1 and 2 (Each cycle: 28 days)
Population: Pharmacokinetic analysis set included all participants who completed at least 1 administration of avelumab and/or M9241, and who provided at least 1 sample with a measurable concentration of avelumab or M9241. Here Number analyzed signifies those participants who were evaluable at the specified time point.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kg | Part B: Maximum Observed Serum Concentration (Cmax) of M9241 | Day 1 | 6.95 ng/mL | Geometric Coefficient of Variation 59.6 |
| Part A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kg | Part B: Maximum Observed Serum Concentration (Cmax) of M9241 | Day 29 | 7.62 ng/mL | Geometric Coefficient of Variation 113 |
Secondary
Part B: Number of Participants With At Least One Positive Anti-drug Antibodies (ADA) of Avelumab and M9241
ADA category of each participant was classified as pre-existing immunoreactivity (positive ADA response at baseline (prior to treatment), treatment-boosted (positive response at baseline with at least one post baseline titer at \>=8-fold baseline titer), or treatment-emergent (TE \[any positive post baseline assay response when baseline results were negative or missing or not reported\]). TE ADA responses were further classified as persistent (treatment-emergent positive ADA response detected in at least 2 consecutive post baseline samples separated by at least a 16-week post baseline period \[based on nominal sampling time\], with no ADA-negative samples in-between or positive response at last ADA sampling time point) and transient (not persistent/indeterminate, regardless of any missing samples).
Time frame: Time from first dose of study treatment up to 443 days
Population: Immunogenicity analysis set included all participants who received at least 1 complete dose (at least 90% of planned dose) of any study treatment \& at least 1 valid ADA result for avelumab or NHS-IL12.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kg | Part B: Number of Participants With At Least One Positive Anti-drug Antibodies (ADA) of Avelumab and M9241 | Avelumab: ADA pre-existing | 0 Participants |
| Part A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kg | Part B: Number of Participants With At Least One Positive Anti-drug Antibodies (ADA) of Avelumab and M9241 | Avelumab: ADA treatment boosted | 0 Participants |
| Part A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kg | Part B: Number of Participants With At Least One Positive Anti-drug Antibodies (ADA) of Avelumab and M9241 | Avelumab: Treatment-Emergent Transient Positive | 0 Participants |
| Part A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kg | Part B: Number of Participants With At Least One Positive Anti-drug Antibodies (ADA) of Avelumab and M9241 | Avelumab: Treatment-Emergent Persistent Positive | 1 Participants |
| Part A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kg | Part B: Number of Participants With At Least One Positive Anti-drug Antibodies (ADA) of Avelumab and M9241 | M9241: ADA pre-existing | 0 Participants |
| Part A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kg | Part B: Number of Participants With At Least One Positive Anti-drug Antibodies (ADA) of Avelumab and M9241 | M9241: ADA treatment boosted | 0 Participants |
| Part A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kg | Part B: Number of Participants With At Least One Positive Anti-drug Antibodies (ADA) of Avelumab and M9241 | M9241: Treatment-Emergent Transient Positive | 1 Participants |
| Part A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kg | Part B: Number of Participants With At Least One Positive Anti-drug Antibodies (ADA) of Avelumab and M9241 | M9241: Treatment-Emergent Persistent Positive | 0 Participants |
Secondary
Part B: Overall Survival (OS) Time
The OS time was defined as the time from treatment day 1 to the date of death due to any cause. The participants who were still alive at the time of data analysis or who were lost to follow-up OS time was censored at the last recorded date that the participant was known to be alive before the data cutoff date. OS was measured using Kaplan-Meier estimates.
Time frame: Time from first dose of study treatment up to 443 days
Population: Full analysis set included all participants who received at least 1 dose of any study treatment.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Part A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kg | Part B: Overall Survival (OS) Time | 4.9 months | 95% Confidence Interval 2.3 |
Secondary
Part B: Progression Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) Criteria Assessed by Investigator
PFS was defined as the time from first treatment day until date of the first documentation of progressive disease (PD) or death due to any cause, whichever occurs first. PD was defined as at least a 20 percent (%) increase in the sum of longest diameter (SLD), taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions. PFS was measured using Kaplan-Meier estimates.
Time frame: Time from first dose administration until progressive disease or death, assessed up to 443 days
Population: Full analysis set included all participants who received at least 1 dose of any study treatment.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Part A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kg | Part B: Progression Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) Criteria Assessed by Investigator | 7.6 weeks | 95% Confidence Interval 7.1 |
Secondary
Part B: Serum Trough Concentration Levels (Ctrough) of Avelumab
Ctrough was defined as the trough or minimum serum concentration.
Time frame: Pre-dose, 1 hour post-dose on Day 15, 29 and 43
Population: Pharmacokinetic analysis set included all participants who completed at least 1 administration of avelumab and/or M9241, and who provided at least 1 sample with a measurable concentration of avelumab or M9241. Here, Overall Number of participants analyzed, signifies those participants who were evaluable for this outcome measure and Number analyzed signifies those participants who were evaluable at the specified time point.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kg | Part B: Serum Trough Concentration Levels (Ctrough) of Avelumab | Day 15 | 54.2 mcg/mL | Geometric Coefficient of Variation 64.9 |
| Part A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kg | Part B: Serum Trough Concentration Levels (Ctrough) of Avelumab | Day 29 | 53.9 mcg/mL | Geometric Coefficient of Variation 217.5 |
| Part A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kg | Part B: Serum Trough Concentration Levels (Ctrough) of Avelumab | Day 43 | 44.6 mcg/mL | Geometric Coefficient of Variation 101.8 |
Secondary
Part B: Serum Trough Concentration Levels (Ctrough) of M9241
Ctrough was defined as the trough or minimum serum concentration.
Time frame: Pre-dose, 1 hour post-dose on Day 1 of cycle 2; Day 1, 27 of cycle 3; Day 1 of cycle 5 (Each cycle: 28 days)
Population: Pharmacokinetic analysis set included all participants who completed at least 1 administration of avelumab and/or M9241, and who provided at least 1 sample with a measurable concentration of avelumab or M9241. Here, Overall Number of participants analyzed, signifies those participants who were evaluable for this outcome measure and Number analyzed signifies those participants who were evaluable at the specified time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kg | Part B: Serum Trough Concentration Levels (Ctrough) of M9241 | Day 29 | 0 ng/mL | Standard Deviation 0 |
| Part A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kg | Part B: Serum Trough Concentration Levels (Ctrough) of M9241 | Day 57 | 0 ng/mL | Standard Deviation 0 |
| Part A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kg | Part B: Serum Trough Concentration Levels (Ctrough) of M9241 | Day 83 | NA ng/mL | — |
| Part A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kg | Part B: Serum Trough Concentration Levels (Ctrough) of M9241 | Day 113 | NA ng/mL | — |
Secondary
Pat A: Number of Participants With Immune-related Best Overall Response (BOR) Using Immune-related Response Criteria Derived From Response Evaluation Criteria in Solid Tumors Version 1.1
BOR: best response of any of immune related complete response (irCR), immune related partial response (irPR), immune related stable disease (irSD) and immune related progressive disease (irPD) recorded from the date of randomization until disease progression or recurrence (taking the smallest measurement recorded since the start of treatment as reference). irCR: Complete disappearance of all tumor lesions (both index and non-index lesions with no new measurable/unmeasurable lesions). irPR: At least 30% reduction from baseline in the sum of the longest diameter (SLD) of all lesions). irSD: SLD of target and new measurable lesions neither irCR, irPR, or irPD. irPD: SLD of target and new measurable lesions increases greater than or equal to \[\>=\] 20%, confirmed by a repeat, consecutive observations at least 4 weeks from the date first documented. Number of participants with immune-related best overall response in each category (irCR, irPR, irSD, irPD) was reported.
Time frame: First dose of study drug up to 1311 days
Population: Full analysis set included all participants who received at least 1 dose of any study treatment.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kg | Pat A: Number of Participants With Immune-related Best Overall Response (BOR) Using Immune-related Response Criteria Derived From Response Evaluation Criteria in Solid Tumors Version 1.1 | Immune-Related Progressive Disease (irPD) | 0 Participants |
| Part A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kg | Pat A: Number of Participants With Immune-related Best Overall Response (BOR) Using Immune-related Response Criteria Derived From Response Evaluation Criteria in Solid Tumors Version 1.1 | Immune-Related Complete Response (irCR) | 0 Participants |
| Part A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kg | Pat A: Number of Participants With Immune-related Best Overall Response (BOR) Using Immune-related Response Criteria Derived From Response Evaluation Criteria in Solid Tumors Version 1.1 | Not evaluable (NE) | 7 Participants |
| Part A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kg | Pat A: Number of Participants With Immune-related Best Overall Response (BOR) Using Immune-related Response Criteria Derived From Response Evaluation Criteria in Solid Tumors Version 1.1 | Immune-Related Partial Response (irPR) | 0 Participants |
| Part A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kg | Pat A: Number of Participants With Immune-related Best Overall Response (BOR) Using Immune-related Response Criteria Derived From Response Evaluation Criteria in Solid Tumors Version 1.1 | Immune-Related Stable Disease (irSD) | 2 Participants |
| Part A Cohort 2: M9241 8 mcg/kg + Avelumab 10 mg/kg | Pat A: Number of Participants With Immune-related Best Overall Response (BOR) Using Immune-related Response Criteria Derived From Response Evaluation Criteria in Solid Tumors Version 1.1 | Immune-Related Progressive Disease (irPD) | 0 Participants |
| Part A Cohort 2: M9241 8 mcg/kg + Avelumab 10 mg/kg | Pat A: Number of Participants With Immune-related Best Overall Response (BOR) Using Immune-related Response Criteria Derived From Response Evaluation Criteria in Solid Tumors Version 1.1 | Immune-Related Stable Disease (irSD) | 2 Participants |
| Part A Cohort 2: M9241 8 mcg/kg + Avelumab 10 mg/kg | Pat A: Number of Participants With Immune-related Best Overall Response (BOR) Using Immune-related Response Criteria Derived From Response Evaluation Criteria in Solid Tumors Version 1.1 | Immune-Related Partial Response (irPR) | 0 Participants |
| Part A Cohort 2: M9241 8 mcg/kg + Avelumab 10 mg/kg | Pat A: Number of Participants With Immune-related Best Overall Response (BOR) Using Immune-related Response Criteria Derived From Response Evaluation Criteria in Solid Tumors Version 1.1 | Not evaluable (NE) | 4 Participants |
| Part A Cohort 2: M9241 8 mcg/kg + Avelumab 10 mg/kg | Pat A: Number of Participants With Immune-related Best Overall Response (BOR) Using Immune-related Response Criteria Derived From Response Evaluation Criteria in Solid Tumors Version 1.1 | Immune-Related Complete Response (irCR) | 1 Participants |
| Part A Cohort 3: M9241 12 mcg/kg + Avelumab 10 mg/kg | Pat A: Number of Participants With Immune-related Best Overall Response (BOR) Using Immune-related Response Criteria Derived From Response Evaluation Criteria in Solid Tumors Version 1.1 | Immune-Related Stable Disease (irSD) | 2 Participants |
| Part A Cohort 3: M9241 12 mcg/kg + Avelumab 10 mg/kg | Pat A: Number of Participants With Immune-related Best Overall Response (BOR) Using Immune-related Response Criteria Derived From Response Evaluation Criteria in Solid Tumors Version 1.1 | Immune-Related Complete Response (irCR) | 0 Participants |
| Part A Cohort 3: M9241 12 mcg/kg + Avelumab 10 mg/kg | Pat A: Number of Participants With Immune-related Best Overall Response (BOR) Using Immune-related Response Criteria Derived From Response Evaluation Criteria in Solid Tumors Version 1.1 | Immune-Related Partial Response (irPR) | 0 Participants |
| Part A Cohort 3: M9241 12 mcg/kg + Avelumab 10 mg/kg | Pat A: Number of Participants With Immune-related Best Overall Response (BOR) Using Immune-related Response Criteria Derived From Response Evaluation Criteria in Solid Tumors Version 1.1 | Immune-Related Progressive Disease (irPD) | 0 Participants |
| Part A Cohort 3: M9241 12 mcg/kg + Avelumab 10 mg/kg | Pat A: Number of Participants With Immune-related Best Overall Response (BOR) Using Immune-related Response Criteria Derived From Response Evaluation Criteria in Solid Tumors Version 1.1 | Not evaluable (NE) | 5 Participants |
| Part A Cohort 4: M9241 16.8 mcg/kg +Avelumab 10 mg/kg | Pat A: Number of Participants With Immune-related Best Overall Response (BOR) Using Immune-related Response Criteria Derived From Response Evaluation Criteria in Solid Tumors Version 1.1 | Not evaluable (NE) | 2 Participants |
| Part A Cohort 4: M9241 16.8 mcg/kg +Avelumab 10 mg/kg | Pat A: Number of Participants With Immune-related Best Overall Response (BOR) Using Immune-related Response Criteria Derived From Response Evaluation Criteria in Solid Tumors Version 1.1 | Immune-Related Complete Response (irCR) | 1 Participants |
| Part A Cohort 4: M9241 16.8 mcg/kg +Avelumab 10 mg/kg | Pat A: Number of Participants With Immune-related Best Overall Response (BOR) Using Immune-related Response Criteria Derived From Response Evaluation Criteria in Solid Tumors Version 1.1 | Immune-Related Progressive Disease (irPD) | 0 Participants |
| Part A Cohort 4: M9241 16.8 mcg/kg +Avelumab 10 mg/kg | Pat A: Number of Participants With Immune-related Best Overall Response (BOR) Using Immune-related Response Criteria Derived From Response Evaluation Criteria in Solid Tumors Version 1.1 | Immune-Related Stable Disease (irSD) | 3 Participants |
| Part A Cohort 4: M9241 16.8 mcg/kg +Avelumab 10 mg/kg | Pat A: Number of Participants With Immune-related Best Overall Response (BOR) Using Immune-related Response Criteria Derived From Response Evaluation Criteria in Solid Tumors Version 1.1 | Immune-Related Partial Response (irPR) | 0 Participants |
| Part A Cohort 5: M9241 16.8 mcg/kg + Avelumab 800 mg | Pat A: Number of Participants With Immune-related Best Overall Response (BOR) Using Immune-related Response Criteria Derived From Response Evaluation Criteria in Solid Tumors Version 1.1 | Immune-Related Stable Disease (irSD) | 3 Participants |
| Part A Cohort 5: M9241 16.8 mcg/kg + Avelumab 800 mg | Pat A: Number of Participants With Immune-related Best Overall Response (BOR) Using Immune-related Response Criteria Derived From Response Evaluation Criteria in Solid Tumors Version 1.1 | Immune-Related Progressive Disease (irPD) | 2 Participants |
| Part A Cohort 5: M9241 16.8 mcg/kg + Avelumab 800 mg | Pat A: Number of Participants With Immune-related Best Overall Response (BOR) Using Immune-related Response Criteria Derived From Response Evaluation Criteria in Solid Tumors Version 1.1 | Immune-Related Complete Response (irCR) | 0 Participants |
| Part A Cohort 5: M9241 16.8 mcg/kg + Avelumab 800 mg | Pat A: Number of Participants With Immune-related Best Overall Response (BOR) Using Immune-related Response Criteria Derived From Response Evaluation Criteria in Solid Tumors Version 1.1 | Not evaluable (NE) | 2 Participants |
| Part A Cohort 5: M9241 16.8 mcg/kg + Avelumab 800 mg | Pat A: Number of Participants With Immune-related Best Overall Response (BOR) Using Immune-related Response Criteria Derived From Response Evaluation Criteria in Solid Tumors Version 1.1 | Immune-Related Partial Response (irPR) | 0 Participants |