Non-Small Cell Lung Cancer, Triple-negative Breast Cancer
Conditions
Brief summary
Part 1of the study will evaluate the safety, pharmacokinetics, pharmacodynamics and immunogenicity of increasing doses of a vaccine-based immunotherapy regimen (VBIR-2) for patients with advanced or metastatic non-small cell lung cancer and metastatic triple-negative breast cancer. Part 2 will evaluate the safety, pharmacokinetics and pharmacodynamics, immunogenicity and preliminary evidence of efficacy of the Expansion dose of VBIR-2 in participants with advanced or metastatic non-small cell lung cancer.
Detailed description
The study is divided into two parts, Dose Escalation (Part 1) in participants with NSCLC and TNBC without acceptable alternative treatment options, followed by Dose Expansion (Part 2) in participants with NSCLC who have progressed on or after treatment with platinum-based chemotherapy and treatment with 1 immune checkpoint inhibitor, given concurrently or sequentially with chemotherapy. Part 1 has been completed.
Interventions
BIOLOGICALPF-06936308
PF-06936308 components will be administered 4 times per cycle. A cycle is 4 months.
Sponsors
Pfizer
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 1:Histological or cytological diagnosis of non-small cell lung cancer or triple-negative breast cancer. Adequate bone marrow, renal and liver function. Part 2: Histological or cytological diagnosis of metastatic non-small cell lung cancer previously treated with 1 or 2 regimens in metastatic setting including a CPI and platinum-based chemotherapy. Adequate bone marrow, renal and liver function.
Exclusion criteria
* Known symptomatic brain metastases * ECOG performance status greater than or equal to 2 * Concurrent immunotherapy * History of or active autoimmune disorders (including but not limited to: myasthenia gravis, thyroiditis, pneumonitis, rheumatoid arthritis, multiple sclerosis, systemic lupus, erythematosus, scleroderma) and other conditions that disorganize or alter the immune system. * History of inflammatory bowel disease. * Current use of any implanted electronic stimulation device, such as cardiac demand pacemakers, automatic implantable cardiac defibrillator, nerve stimulators, or deep brain stimulators. * Presence of any surgical or traumatic metal implants at the site of administration
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Laboratory Abnormalities in Chemistry (Grade 3 or 4) | Baseline up to 6 months after EOT (22 months in maximum) | Chemistry abnormalities (graded per NCI CTCAE v5.0: Grade 3: severe AE; Grade 4: life-threatening consequences, urgent intervention indicated) in at least 1 participant with data in the categories are presented here. Chemistry parameters included aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, sodium, potassium, magnesium, total chloride, total calcium, total bilirubin, blood urea nitrogen (or urea), creatinine, uric acid, glucose (nonfasted), albumin, phosphorous or phosphate, lactate dehydrogenase, lipase, amylase, bicarbonate or carbon dioxide, total protein, TSH (reflex free T4 and free T3). |
| Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Baseline up to 6 months after End of Treatment (EOT; 22 months in maximum) | An AE was any untoward medical occurrence in a clinical investigation where participant administered a product; the event did not need to have a causal relationship with the treatment. Treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. An SAE was any untoward medical occurrence at any dose that resulted in death; was life threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in congenital anomaly/birth defect or considered to be an important medical event. AEs included both SAEs and non-serious AEs. |
| Number of Participants With Laboratory Abnormalities in Urinalysis (Grade 3 or 4) | Baseline up to 6 months after EOT (22 months in maximum) | Urinalysis abnormalities (graded per NCI CTCAE v5.0: Grade 3: severe AE; Grade 4: life-threatening consequences, urgent intervention indicated) in at least 1 participant with data in the categories are presented here. Urine parameters included urine protein and urine blood. |
| Number of Participants With AEs as Graded by National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0) (Grade ≥3) | Baseline up to 6 months after EOT (22 months in maximum) | An AE was any untoward medical occurrence in a clinical investigation participant administered a product; the event did not need to have a causal relationship with the treatment. Treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. Grades of AEs were defined by NCI CTCAE v5.0. Grade 1 = asymptomatic/mild symptoms, clinical or diagnostic observations only, intervention not indicated; Grade 2 = minimal, local or noninvasive intervention indicated, limiting age-appropriate instrumental activities of daily living (ADL); Grade 3 = severe or medically significant but not immediately life-threatening, hospitalization of prolongation of hospitalization indicated; disabling limiting self-care ADL; Grade 4 = events with life-threatening consequences, urgent intervention indicated; Grade 5 = death related to AE. |
| Number of Participants With AEs Leading to Discontinuation or Dose Reduction | Baseline up to 6 months after EOT (22 months in maximum) | An AE was any untoward medical occurrence in a clinical investigation where participant administered a product; the event did not need to have a causal relationship with the treatment. |
| Number of Participants With Dose-Limiting Toxicities (DLTs) | The first 28 days following the first AdC68 vaccination (Cycle 1 Day 1) | AEs in the first 28 d (days) following the first AdC68 vaccination that were considered possibly related to study treatment and not to disease/progression were DLTs: Grade≥3 neutropenia lasting\>7 d, febrile neutropenia, Grade≥3 neutropenic infection, Grade≥3 thrombocytopenia with Grade≥2 clinically significant bleeding, Grade≥3 anemia lasting \>7 d, Grade≥3 lymphopenia lasting\>14 d; Grade≥3 lab abnormalities associated with symptoms or worsening of an existing condition or that suggested a new disease process or that required additional active management, Grade≥3 AEs considered non-hematologic, non-hepatic major organ toxicity, Grade 3 flu-like symptoms lasting\>3 d, fever of \>40.0 degree Celsius lasting\>3 d, concurrent aspartate aminotransferase or alanine aminotransferase \>3x upper limit of normal (ULN) and total bilirubin \>2x ULN (potential Hy's law case). Other clinically important or persistent toxicities at discretion of investigator and Pfizer. |
| Number of Participants With Laboratory Abnormalities in Hematology and Coagulation (Grade 3 or 4) | Baseline up to 6 months after EOT (22 months in maximum) | Laboratory abnormalities (graded per NCI CTCAE v5.0: Grade 3: severe AE; Grade 4: life-threatening consequences, urgent intervention indicated) in at least 1 participant with data in the categories are presented here. Hematology parameters included hemoglobin, platelets, white blood cell (WBC) count, neutrophils, eosinophils, monocytes, basophils and lymphocytes. Coagulation should include prothrombin time (PT) or international normalized ratio (INR) and activated partial thromboplastin time (APTT). |
| Proportion of Participants Who Achieved Complete Response, Partial Response or Stable Disease for More Than 6 Months Using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 Criteria (Part 2) | Performed every 8 weeks from baseline up to Week 32 | Clinical Benefit Rate (CBR) is defined as the proportion of participants who achieved anti-tumor responses of Complete Response (CR), Partial Response (PR), or Stable Disease (SD) for \>6 months. CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All target nodes must decrease to normal size (short axis \<10 mm). All target lesions must be assessed. PR was defined as ≥30% decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease and no new lesions. All target lesions must be assessed. SD: Does not qualify for CR, PR or Progression. SD can follow PR only in the rare case that the sum increases by \<20% from the nadir, but enough that a previously documented 30% decrease no longer holds. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) Using RECIST v1.1 | Performed every 8 weeks from baseline up to Week 32 | ORR was defined as the percentage of participants with best overall response based assessment of CR or PR according to RECIST v1.1. Per RECIST v1.1: CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All target nodes must decrease to normal size (short axis \<10 mm). All target lesions must be assessed. PR was defined as ≥30% decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease and no new lesions. All target lesions must be assessed. |
| Progression-Free Survival (PFS) Using RECIST v1.1 With NSCLC | Performed every 3 weeks after treatment discontinuation until death, participant refusal, or lost to follow-up (telephone contact acceptable). | PFS was defined as the time from start date to date of first documentation of progression, or death due to any cause. Progression was defined as the appearance of local, regional or distant disease of the same type after complete response or progression of pre-existing lesions. |
| PFS Using RECIST v1.1 With TNBC | Performed every 3 weeks after treatment discontinuation until death, participant refusal, or lost to follow-up (telephone contact acceptable). | PFS was defined as the time from start date to date of first documentation of progression, or death due to any cause. Progression was defined as the appearance of local, regional or distant disease of the same type after complete response or progression of pre existing lesions. |
| Number of Participants With Anti-Drug Antibody (ADA) Against Sasanlimab | Cycle 1: on Day 1, Day 29, and Day 85; Cycle 2: on Day 29; at the EOT visit, and 2, 4 and 6 months after EOT. Samples to be collected on dosing days were obtained within 6 hours prior to sasanlimab dosing. | Participants were considered ADA-positive if (1) baseline titer was missing or negative and participant had ≥1 post-treatment positive titer (treatment-induced), or (2) positive titer at baseline and had a ratio of ≥4 in titer (dilution) to baseline in ≥1 post-treatment sample (treatment-boosted). |
| Maximum Observed Serum Concentration (Cmax) of Sasanlimab | Cycle 1: at pre-dose on Days 1, 3-6, 8, 15, 22, 29, 57, 85; Cycle 2: at pre-dose on Day 1 and Day 29; EOT; Months 2, 4, and 6 after EOT visit | Cmax was defined as the maximum observed serum concentration. |
| Number of Participants With ADA Against Tremelimumab | Cycle 1: on Day 1, Day 29, and Day 85; Cycle 2: on Day 29; at the EOT visit, and 2, 4 and 6 months after EOT. Samples collected on dosing days were obtained within 6 hours prior to tremelimumab dosing. | Participants were considered ADA-positive if (1) baseline titer was missing or negative and participant had ≥1 post-treatment positive titer (treatment-induced), or (2) positive titer at baseline and had a ratio of ≥4 in titer (dilution) to baseline in ≥1 post-treatment sample (treatment-boosted). |
| Number of Participants With NAb Against Tremelimumab | Cycle 1: on Day 1, Day 29, and Day 85; Cycle 2: on Day 29; at the EOT visit, and 2, 4 and 6 months after EOT. Samples to be collected on dosing days were obtained within 6 hours prior to tremelimumab dosing. | A participant was NAb positive if (1) baseline titer was missing or negative and participant had ≥1 post-treatment positive titer (treatment-induced), or (2) positive titer at baseline and had a ratio of ≥4 in titer (dilution) to baseline in ≥1 post-treatment sample (treatment-boosted). Participants who were either (1) an ADA-negative participant or (2) an ADA-positive participant without treatment-induced or treatment-boosted NAb response were considered as NAb negative. NAb evaluation was not considered as meaningful taken that treatment-induced ADA was found in only 1 participant. Thus, NAb to tremelimumab was not examined. |
| Titers of Treatment-Induced ADA and NAb Against Sasanlimab | Cycle 1: at Day 1, Day 29, and Day 85; Cycle 2: at Day 29; at the EOT visit, and 2, 4 and 6 months after EOT. Samples to be collected on dosing days were obtained within 6 hours prior to sasanlimab dosing. | Titers were measured in terms of 1/dilution. Only the samples tested positive for ADA were to be further tested for Nab. Treatment-induced ADA: baseline titer is missing or negative and participant has \>= 1 post-treatment positive titer. Treatment-induced NAb: baseline titer was missing or negative and participant had ≥1 post-treatment positive titer. |
| Titers of Treatment-Induced ADA and NAb Against Tremelimumab | Cycle 1: at Day 1, Day 29, and Day 85; Cycle 2: at Day 29; at the EOT visit, and 2, 4 and 6 months after EOT. Samples to be collected on dosing days were obtained within 6 hours prior to tremelimumab dosing. | Titers were measured in terms of 1/dilution. Only the samples tested positive for ADA were to be further tested for Nab. Treatment-induced ADA: baseline titer is missing or negative and participant has \>= 1 post-treatment positive titer. Treatment-induced NAb: baseline titer was missing or negative and participant had ≥1 post-treatment positive titer. NAb was not examined as the evaluation was not meaningful considering only 1 participant had treatment-induced ADA. |
| Number of Participants With Neutralizing Antibody (NAb) Against Sasanlimab | Cycle 1: on Day 1, Day 29, and Day 85; Cycle 2: on Day 29; at the EOT visit, and 2, 4 and 6 months after EOT. Samples to be collected on dosing days were obtained within 6 hours prior to sasanlimab dosing. | A participant was NAb positive if (1) baseline titer was missing or negative and participant had ≥1 post-treatment positive titer (treatment-induced), or (2) positive titer at baseline and had a ratio of ≥4 in titer (dilution) to baseline in ≥1 post-treatment sample (treatment-boosted). Participants who were either (1) an ADA-negative participant or (2) an ADA-positive participant without treatment-induced or treatment-boosted NAb response were considered as NAb negative. |
| Cmax of Tremelimumab | Cycle 1: at pre-dose on Days 1, 3-6, 8, 15, 22, 29, 57, 85; Cycle 2: at pre-dose on Day 1 and Day 29; EOT; Months 2, 4 and 6 after EOT visit | Cmax was defined as the maximum observed serum concentration. |
| Time to Maximum Concentration (Tmax) of Sasanlimab | Cycle 1: at pre-dose on Days 1, 3-6, 8, 15, 22, 29, 57, 85; Cycle 2: at pre-dose on Day 1 and Day 29; EOT; Months 2, 4 and 6 after EOT visit | Tmax was defined as the time to reach maximum observed serum concentration. |
| Tmax of Tremelimumab | Cycle 1: at pre-dose on Days 1, 3-6, 8, 15, 22, 29, 57, 85; Cycle 2: at pre-dose on Day 1 and Day 29; EOT; Months 2, 4 and 6 after EOT visit | Tmax was defined as the time to reach maximum observed serum concentration. |
| Area Under the Curve From Time 0 Extrapolated to Infinity (AUCinf) of Sasanlimab | Cycle 1: at pre-dose on Days 1, 3-6, 8, 15, 22, 29, 57, 85; Cycle 2: at pre-dose on Day 1 and Day 29; EOT; Months 2, 4 and 6 after EOT visit | AUCinf was defined as area under the concentration time curve from time 0 extrapolated to infinity. AUCinf of sasanlimab was not reported due to the limited data points during elimination phase, and the lack of a well-characterized terminal phase. A well-characterized terminal phase was defined as one with at least 3 data points, r\^2 ≥0.9, and percent of AUCextrap% ≤20%. |
| AUCinf of Tremelimumab | Cycle 1: at pre-dose on Days 1, 3-6, 8, 15, 22, 29, 57, 85; Cycle 2: at pre-dose on Day 1 and Day 29; EOT; Months 2, 4 and 6 after EOT visit | AUCinf was defined as area under the concentration time curve from time 0 extrapolated to infinity. AUCinf of tremelimumab was not reported due to the limited data points during elimination phase, and the lack of a well-characterized terminal phase. A well-characterized terminal phase was defined as one with at least 3 data points, r\^2 ≥0.9, and percent of AUCextrap% ≤20%. |
| Trough Concentrations After Multiple Dosing (Ctrough) of Sasanlimab | Cycle 1: at pre-dose on Days 1, 3-6, 8, 15, 22, 29, 57, 85; Cycle 2: at pre-dose on Day 1 and Day 29; Months 2, 4, 6 after EOT visit | Ctrough was defined as the drug concentration observed at the last planned timepoint prior to dosing. Ctrough was not calculated for sasanlimab because trough concentration prior to the fifth dose (on Cycle 2 Day 1) were not collected for any participants in Cohorts 4A or 5A. |
| Ctrough of Tremelimumab | Cycle 1: at pre-dose on Days 1, 3-6, 8, 15, 22, 29, 57, 85; Cycle 2: at pre-dose on Day 1 | Ctrough was defined as the drug concentration observed at the last planned timepoint prior to dosing. |
Countries
United States
Participant flow
Pre-assignment details
A total of 55 participants were screened and 36 of them were enrolled and treated in this study.
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1A Adenovirus C68 (AdC68) 2X10^11 Viral Particles (VP) + Plasmid DNA (pDNA) 5 mg Participants with advanced non-small cell lung cancer (NSCLC) or metastatic triple negative breast cancer (mTNBC) in Cohort 1A received 2 repeated cycles of treatment, including AdC68 2x10\^11 VP intramuscularly (IM) on Day 1 of Cycles 1 and 2, and pDNA 5 mg IM on Days 29, 57, and 85 of Cycles 1 and 2. | 3 |
| Cohort 2A AdC68 6X10^11 VP + pDNA 5 mg Participants with advanced NSCLC or mTNBC in Cohort 2A received 2 repeated cycles of treatment, including AdC68 6x10\^11 VP IM on Day 1 of Cycles 1 and 2, and pDNA 5 mg IM on Days 29, 57, and 85 of Cycles 1 and 2. | 5 |
| Cohort 3A AdC68 6X10^11 VP + pDNA 5 mg + Tremelimumab (Treme) 40 mg Participants with advanced NSCLC or mTNBC in Cohort 3A received 2 repeated cycles of treatment, including AdC68 6x10\^11 VP IM on Day 1 of Cycles 1 and 2, pDNA 5 mg IM and treme 40 mg subcutaneously (SC) on Days 29, 57, and 85 of Cycles 1 and 2. Treme was administered after AdC68 or pDNA. | 3 |
| Cohort 4A AdC68 6X10^11 VP + pDNA 5 mg + Treme 40 mg + Sasanlimab (Sasan) 130 mg Participants with advanced NSCLC or mTNBC in Cohort 4A received 2 repeated cycles of treatment, including AdC68 6x10\^11 VP IM on Day 1 of Cycles 1 and 2; pDNA 5 mg IM, treme 40 mg SC, and sasan 130 mg SC on Days 29, 57, and 85 of Cycles 1 and 2. Sasan was administered after AdC68 or pDNA and after Treme. | 4 |
| Cohort 5A AdC68 6X10^11 VP + pDNA 5 mg + Treme 40 mg + Sasan 300 mg Participants with advanced NSCLC or mTNBC in Cohort 5A received 2 repeated cycles of treatment, including AdC68 6x10\^11 VP IM on Day 1 of Cycles 1 and 2; pDNA 5 mg IM, treme 40 mg SC, and sasan 300 mg SC on Days 29, 57, and 85 of Cycles 1 and 2. Sasan was administered after AdC68 or pDNA and after treme. | 5 |
| Cohort 6A AdC68 6X10^11 VP + pDNA 5 mg + Treme 80 mg + Sasan 300 mg Participants with advanced NSCLC or mTNBC in Cohort 6A received 2 repeated cycles of treatment, including AdC68 6x10\^11 VP IM on Day 1 of Cycles 1 and 2; pDNA 5 mg IM, treme 80 mg SC, and sasan 300 mg SC on Days 29, 57, and 85 of Cycles 1 and 2. Sasan was administered after AdC68 or pDNA and after treme. | 16 |
| Total | 36 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Long-Term Follow-up Phase | Death | 2 | 4 | 2 | 3 | 2 | 6 |
| Long-Term Follow-up Phase | Study Terminated by Sponsor | 0 | 0 | 1 | 1 | 2 | 8 |
| Long-Term Follow-up Phase | Withdrawal by Subject | 1 | 1 | 0 | 0 | 1 | 2 |
| Treatment Phase | Adverse Event | 0 | 0 | 0 | 0 | 0 | 2 |
| Treatment Phase | Death | 2 | 0 | 0 | 0 | 1 | 0 |
| Treatment Phase | Global Deterioration of Health Status | 1 | 0 | 0 | 0 | 0 | 2 |
| Treatment Phase | Other | 0 | 1 | 0 | 0 | 0 | 1 |
| Treatment Phase | Progressive Disease | 0 | 4 | 3 | 4 | 4 | 9 |
| Treatment Phase | Study Terminated by Sponsor | 0 | 0 | 0 | 0 | 0 | 1 |
| Treatment Phase | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Cohort 1A Adenovirus C68 (AdC68) 2X10^11 Viral Particles (VP) + Plasmid DNA (pDNA) 5 mg | Cohort 2A AdC68 6X10^11 VP + pDNA 5 mg | Cohort 3A AdC68 6X10^11 VP + pDNA 5 mg + Tremelimumab (Treme) 40 mg | Cohort 4A AdC68 6X10^11 VP + pDNA 5 mg + Treme 40 mg + Sasanlimab (Sasan) 130 mg | Cohort 5A AdC68 6X10^11 VP + pDNA 5 mg + Treme 40 mg + Sasan 300 mg | Cohort 6A AdC68 6X10^11 VP + pDNA 5 mg + Treme 80 mg + Sasan 300 mg | Total |
|---|---|---|---|---|---|---|---|
| Age, Customized 18-44 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 3 Participants | 4 Participants |
| Age, Customized <18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized 45-64 years | 2 Participants | 2 Participants | 1 Participants | 4 Participants | 3 Participants | 7 Participants | 19 Participants |
| Age, Customized ≥65 years | 1 Participants | 3 Participants | 2 Participants | 0 Participants | 1 Participants | 6 Participants | 13 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants | 5 Participants | 3 Participants | 4 Participants | 5 Participants | 16 Participants | 36 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized Multiracial | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Other | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Unknown | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized White | 3 Participants | 5 Participants | 3 Participants | 4 Participants | 2 Participants | 15 Participants | 32 Participants |
| Sex: Female, Male Female | 1 Participants | 3 Participants | 3 Participants | 4 Participants | 2 Participants | 11 Participants | 24 Participants |
| Sex: Female, Male Male | 2 Participants | 2 Participants | 0 Participants | 0 Participants | 3 Participants | 5 Participants | 12 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 | 2 / 3 | 4 / 5 | 2 / 3 | 3 / 4 | 2 / 5 | 6 / 16 |
| other Total, other adverse events | 2 / 3 | 5 / 5 | 3 / 3 | 4 / 4 | 5 / 5 | 16 / 16 |
| serious Total, serious adverse events | 2 / 3 | 4 / 5 | 2 / 3 | 3 / 4 | 1 / 5 | 6 / 16 |
Outcome results
Primary
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
An AE was any untoward medical occurrence in a clinical investigation where participant administered a product; the event did not need to have a causal relationship with the treatment. Treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. An SAE was any untoward medical occurrence at any dose that resulted in death; was life threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in congenital anomaly/birth defect or considered to be an important medical event. AEs included both SAEs and non-serious AEs.
Time frame: Baseline up to 6 months after End of Treatment (EOT; 22 months in maximum)
Population: The safety analysis set included all enrolled participants who received at least 1 dose of one of the components of the regimen.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1A Adenovirus C68 (AdC68) 2X10^11 Viral Particles (VP) + Plasmid DNA (pDNA) 5 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Number of participants with all-causality AEs | 3 Participants |
| Cohort 1A Adenovirus C68 (AdC68) 2X10^11 Viral Particles (VP) + Plasmid DNA (pDNA) 5 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Number of participants with treatment-related AEs | 1 Participants |
| Cohort 1A Adenovirus C68 (AdC68) 2X10^11 Viral Particles (VP) + Plasmid DNA (pDNA) 5 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Number of participants with all-causality SAEs | 2 Participants |
| Cohort 1A Adenovirus C68 (AdC68) 2X10^11 Viral Particles (VP) + Plasmid DNA (pDNA) 5 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Number of participants with treatment-related SAEs | 0 Participants |
| Cohort 2A AdC68 6X10^11 VP + pDNA 5 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Number of participants with all-causality SAEs | 4 Participants |
| Cohort 2A AdC68 6X10^11 VP + pDNA 5 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Number of participants with treatment-related AEs | 5 Participants |
| Cohort 2A AdC68 6X10^11 VP + pDNA 5 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Number of participants with all-causality AEs | 5 Participants |
| Cohort 2A AdC68 6X10^11 VP + pDNA 5 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Number of participants with treatment-related SAEs | 0 Participants |
| Cohort 3A AdC68 6X10^11 VP + pDNA 5 mg + Tremelimumab (Treme) 40 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Number of participants with treatment-related SAEs | 0 Participants |
| Cohort 3A AdC68 6X10^11 VP + pDNA 5 mg + Tremelimumab (Treme) 40 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Number of participants with all-causality SAEs | 2 Participants |
| Cohort 3A AdC68 6X10^11 VP + pDNA 5 mg + Tremelimumab (Treme) 40 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Number of participants with treatment-related AEs | 1 Participants |
| Cohort 3A AdC68 6X10^11 VP + pDNA 5 mg + Tremelimumab (Treme) 40 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Number of participants with all-causality AEs | 3 Participants |
| Cohort 4A AdC68 6X10^11 VP + pDNA 5 mg + Treme 40 mg + Sasanlimab (Sasan) 130 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Number of participants with all-causality AEs | 4 Participants |
| Cohort 4A AdC68 6X10^11 VP + pDNA 5 mg + Treme 40 mg + Sasanlimab (Sasan) 130 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Number of participants with treatment-related SAEs | 0 Participants |
| Cohort 4A AdC68 6X10^11 VP + pDNA 5 mg + Treme 40 mg + Sasanlimab (Sasan) 130 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Number of participants with treatment-related AEs | 4 Participants |
| Cohort 4A AdC68 6X10^11 VP + pDNA 5 mg + Treme 40 mg + Sasanlimab (Sasan) 130 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Number of participants with all-causality SAEs | 3 Participants |
| Cohort 5A AdC68 6X10^11 VP + pDNA 5 mg + Treme 40 mg + Sasan 300 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Number of participants with all-causality SAEs | 1 Participants |
| Cohort 5A AdC68 6X10^11 VP + pDNA 5 mg + Treme 40 mg + Sasan 300 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Number of participants with treatment-related SAEs | 0 Participants |
| Cohort 5A AdC68 6X10^11 VP + pDNA 5 mg + Treme 40 mg + Sasan 300 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Number of participants with treatment-related AEs | 3 Participants |
| Cohort 5A AdC68 6X10^11 VP + pDNA 5 mg + Treme 40 mg + Sasan 300 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Number of participants with all-causality AEs | 5 Participants |
| Cohort 6A AdC68 6X10^11 VP + pDNA 5 mg + Treme 80 mg + Sasan 300 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Number of participants with treatment-related AEs | 14 Participants |
| Cohort 6A AdC68 6X10^11 VP + pDNA 5 mg + Treme 80 mg + Sasan 300 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Number of participants with all-causality SAEs | 6 Participants |
| Cohort 6A AdC68 6X10^11 VP + pDNA 5 mg + Treme 80 mg + Sasan 300 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Number of participants with treatment-related SAEs | 0 Participants |
| Cohort 6A AdC68 6X10^11 VP + pDNA 5 mg + Treme 80 mg + Sasan 300 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Number of participants with all-causality AEs | 16 Participants |
Primary
Number of Participants With AEs as Graded by National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0) (Grade ≥3)
An AE was any untoward medical occurrence in a clinical investigation participant administered a product; the event did not need to have a causal relationship with the treatment. Treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. Grades of AEs were defined by NCI CTCAE v5.0. Grade 1 = asymptomatic/mild symptoms, clinical or diagnostic observations only, intervention not indicated; Grade 2 = minimal, local or noninvasive intervention indicated, limiting age-appropriate instrumental activities of daily living (ADL); Grade 3 = severe or medically significant but not immediately life-threatening, hospitalization of prolongation of hospitalization indicated; disabling limiting self-care ADL; Grade 4 = events with life-threatening consequences, urgent intervention indicated; Grade 5 = death related to AE.
Time frame: Baseline up to 6 months after EOT (22 months in maximum)
Population: The safety analysis set included all enrolled participants who received at least 1 dose of one of the components of the regimen.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1A Adenovirus C68 (AdC68) 2X10^11 Viral Particles (VP) + Plasmid DNA (pDNA) 5 mg | Number of Participants With AEs as Graded by National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0) (Grade ≥3) | Grade 3 or Grade 4 (all-causality) | 1 Participants |
| Cohort 1A Adenovirus C68 (AdC68) 2X10^11 Viral Particles (VP) + Plasmid DNA (pDNA) 5 mg | Number of Participants With AEs as Graded by National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0) (Grade ≥3) | Grade 3 or Grade 4 (treatment-related) | 0 Participants |
| Cohort 1A Adenovirus C68 (AdC68) 2X10^11 Viral Particles (VP) + Plasmid DNA (pDNA) 5 mg | Number of Participants With AEs as Graded by National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0) (Grade ≥3) | Grade 5 (all-causality) | 2 Participants |
| Cohort 1A Adenovirus C68 (AdC68) 2X10^11 Viral Particles (VP) + Plasmid DNA (pDNA) 5 mg | Number of Participants With AEs as Graded by National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0) (Grade ≥3) | Grade 5 (treatment-related) | 0 Participants |
| Cohort 2A AdC68 6X10^11 VP + pDNA 5 mg | Number of Participants With AEs as Graded by National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0) (Grade ≥3) | Grade 5 (all-causality) | 4 Participants |
| Cohort 2A AdC68 6X10^11 VP + pDNA 5 mg | Number of Participants With AEs as Graded by National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0) (Grade ≥3) | Grade 3 or Grade 4 (treatment-related) | 0 Participants |
| Cohort 2A AdC68 6X10^11 VP + pDNA 5 mg | Number of Participants With AEs as Graded by National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0) (Grade ≥3) | Grade 3 or Grade 4 (all-causality) | 1 Participants |
| Cohort 2A AdC68 6X10^11 VP + pDNA 5 mg | Number of Participants With AEs as Graded by National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0) (Grade ≥3) | Grade 5 (treatment-related) | 0 Participants |
| Cohort 3A AdC68 6X10^11 VP + pDNA 5 mg + Tremelimumab (Treme) 40 mg | Number of Participants With AEs as Graded by National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0) (Grade ≥3) | Grade 5 (treatment-related) | 0 Participants |
| Cohort 3A AdC68 6X10^11 VP + pDNA 5 mg + Tremelimumab (Treme) 40 mg | Number of Participants With AEs as Graded by National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0) (Grade ≥3) | Grade 5 (all-causality) | 2 Participants |
| Cohort 3A AdC68 6X10^11 VP + pDNA 5 mg + Tremelimumab (Treme) 40 mg | Number of Participants With AEs as Graded by National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0) (Grade ≥3) | Grade 3 or Grade 4 (treatment-related) | 0 Participants |
| Cohort 3A AdC68 6X10^11 VP + pDNA 5 mg + Tremelimumab (Treme) 40 mg | Number of Participants With AEs as Graded by National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0) (Grade ≥3) | Grade 3 or Grade 4 (all-causality) | 0 Participants |
| Cohort 4A AdC68 6X10^11 VP + pDNA 5 mg + Treme 40 mg + Sasanlimab (Sasan) 130 mg | Number of Participants With AEs as Graded by National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0) (Grade ≥3) | Grade 3 or Grade 4 (all-causality) | 1 Participants |
| Cohort 4A AdC68 6X10^11 VP + pDNA 5 mg + Treme 40 mg + Sasanlimab (Sasan) 130 mg | Number of Participants With AEs as Graded by National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0) (Grade ≥3) | Grade 5 (treatment-related) | 0 Participants |
| Cohort 4A AdC68 6X10^11 VP + pDNA 5 mg + Treme 40 mg + Sasanlimab (Sasan) 130 mg | Number of Participants With AEs as Graded by National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0) (Grade ≥3) | Grade 3 or Grade 4 (treatment-related) | 0 Participants |
| Cohort 4A AdC68 6X10^11 VP + pDNA 5 mg + Treme 40 mg + Sasanlimab (Sasan) 130 mg | Number of Participants With AEs as Graded by National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0) (Grade ≥3) | Grade 5 (all-causality) | 1 Participants |
| Cohort 5A AdC68 6X10^11 VP + pDNA 5 mg + Treme 40 mg + Sasan 300 mg | Number of Participants With AEs as Graded by National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0) (Grade ≥3) | Grade 5 (all-causality) | 1 Participants |
| Cohort 5A AdC68 6X10^11 VP + pDNA 5 mg + Treme 40 mg + Sasan 300 mg | Number of Participants With AEs as Graded by National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0) (Grade ≥3) | Grade 5 (treatment-related) | 0 Participants |
| Cohort 5A AdC68 6X10^11 VP + pDNA 5 mg + Treme 40 mg + Sasan 300 mg | Number of Participants With AEs as Graded by National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0) (Grade ≥3) | Grade 3 or Grade 4 (treatment-related) | 1 Participants |
| Cohort 5A AdC68 6X10^11 VP + pDNA 5 mg + Treme 40 mg + Sasan 300 mg | Number of Participants With AEs as Graded by National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0) (Grade ≥3) | Grade 3 or Grade 4 (all-causality) | 2 Participants |
| Cohort 6A AdC68 6X10^11 VP + pDNA 5 mg + Treme 80 mg + Sasan 300 mg | Number of Participants With AEs as Graded by National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0) (Grade ≥3) | Grade 3 or Grade 4 (treatment-related) | 1 Participants |
| Cohort 6A AdC68 6X10^11 VP + pDNA 5 mg + Treme 80 mg + Sasan 300 mg | Number of Participants With AEs as Graded by National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0) (Grade ≥3) | Grade 5 (all-causality) | 6 Participants |
| Cohort 6A AdC68 6X10^11 VP + pDNA 5 mg + Treme 80 mg + Sasan 300 mg | Number of Participants With AEs as Graded by National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0) (Grade ≥3) | Grade 5 (treatment-related) | 0 Participants |
| Cohort 6A AdC68 6X10^11 VP + pDNA 5 mg + Treme 80 mg + Sasan 300 mg | Number of Participants With AEs as Graded by National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0) (Grade ≥3) | Grade 3 or Grade 4 (all-causality) | 2 Participants |
Primary
Number of Participants With AEs Leading to Discontinuation or Dose Reduction
An AE was any untoward medical occurrence in a clinical investigation where participant administered a product; the event did not need to have a causal relationship with the treatment.
Time frame: Baseline up to 6 months after EOT (22 months in maximum)
Population: The safety analysis set included all enrolled participants who received at least 1 dose of one of the components of the regimen.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1A Adenovirus C68 (AdC68) 2X10^11 Viral Particles (VP) + Plasmid DNA (pDNA) 5 mg | Number of Participants With AEs Leading to Discontinuation or Dose Reduction | Number of participants with dose reduction or temporary discontinuations | 0 Participants |
| Cohort 1A Adenovirus C68 (AdC68) 2X10^11 Viral Particles (VP) + Plasmid DNA (pDNA) 5 mg | Number of Participants With AEs Leading to Discontinuation or Dose Reduction | Number of participants with permanent discontinuations | 2 Participants |
| Cohort 2A AdC68 6X10^11 VP + pDNA 5 mg | Number of Participants With AEs Leading to Discontinuation or Dose Reduction | Number of participants with permanent discontinuations | 0 Participants |
| Cohort 2A AdC68 6X10^11 VP + pDNA 5 mg | Number of Participants With AEs Leading to Discontinuation or Dose Reduction | Number of participants with dose reduction or temporary discontinuations | 0 Participants |
| Cohort 3A AdC68 6X10^11 VP + pDNA 5 mg + Tremelimumab (Treme) 40 mg | Number of Participants With AEs Leading to Discontinuation or Dose Reduction | Number of participants with permanent discontinuations | 2 Participants |
| Cohort 3A AdC68 6X10^11 VP + pDNA 5 mg + Tremelimumab (Treme) 40 mg | Number of Participants With AEs Leading to Discontinuation or Dose Reduction | Number of participants with dose reduction or temporary discontinuations | 0 Participants |
| Cohort 4A AdC68 6X10^11 VP + pDNA 5 mg + Treme 40 mg + Sasanlimab (Sasan) 130 mg | Number of Participants With AEs Leading to Discontinuation or Dose Reduction | Number of participants with permanent discontinuations | 1 Participants |
| Cohort 4A AdC68 6X10^11 VP + pDNA 5 mg + Treme 40 mg + Sasanlimab (Sasan) 130 mg | Number of Participants With AEs Leading to Discontinuation or Dose Reduction | Number of participants with dose reduction or temporary discontinuations | 0 Participants |
| Cohort 5A AdC68 6X10^11 VP + pDNA 5 mg + Treme 40 mg + Sasan 300 mg | Number of Participants With AEs Leading to Discontinuation or Dose Reduction | Number of participants with permanent discontinuations | 1 Participants |
| Cohort 5A AdC68 6X10^11 VP + pDNA 5 mg + Treme 40 mg + Sasan 300 mg | Number of Participants With AEs Leading to Discontinuation or Dose Reduction | Number of participants with dose reduction or temporary discontinuations | 2 Participants |
| Cohort 6A AdC68 6X10^11 VP + pDNA 5 mg + Treme 80 mg + Sasan 300 mg | Number of Participants With AEs Leading to Discontinuation or Dose Reduction | Number of participants with permanent discontinuations | 2 Participants |
| Cohort 6A AdC68 6X10^11 VP + pDNA 5 mg + Treme 80 mg + Sasan 300 mg | Number of Participants With AEs Leading to Discontinuation or Dose Reduction | Number of participants with dose reduction or temporary discontinuations | 2 Participants |
Primary
Number of Participants With Dose-Limiting Toxicities (DLTs)
AEs in the first 28 d (days) following the first AdC68 vaccination that were considered possibly related to study treatment and not to disease/progression were DLTs: Grade≥3 neutropenia lasting\>7 d, febrile neutropenia, Grade≥3 neutropenic infection, Grade≥3 thrombocytopenia with Grade≥2 clinically significant bleeding, Grade≥3 anemia lasting \>7 d, Grade≥3 lymphopenia lasting\>14 d; Grade≥3 lab abnormalities associated with symptoms or worsening of an existing condition or that suggested a new disease process or that required additional active management, Grade≥3 AEs considered non-hematologic, non-hepatic major organ toxicity, Grade 3 flu-like symptoms lasting\>3 d, fever of \>40.0 degree Celsius lasting\>3 d, concurrent aspartate aminotransferase or alanine aminotransferase \>3x upper limit of normal (ULN) and total bilirubin \>2x ULN (potential Hy's law case). Other clinically important or persistent toxicities at discretion of investigator and Pfizer.
Time frame: The first 28 days following the first AdC68 vaccination (Cycle 1 Day 1)
Population: The safety analysis set included all enrolled participants who received at least 1 dose of one of the components of the regimen.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1A Adenovirus C68 (AdC68) 2X10^11 Viral Particles (VP) + Plasmid DNA (pDNA) 5 mg | Number of Participants With Dose-Limiting Toxicities (DLTs) | 0 Participants |
| Cohort 2A AdC68 6X10^11 VP + pDNA 5 mg | Number of Participants With Dose-Limiting Toxicities (DLTs) | 0 Participants |
| Cohort 3A AdC68 6X10^11 VP + pDNA 5 mg + Tremelimumab (Treme) 40 mg | Number of Participants With Dose-Limiting Toxicities (DLTs) | 0 Participants |
| Cohort 4A AdC68 6X10^11 VP + pDNA 5 mg + Treme 40 mg + Sasanlimab (Sasan) 130 mg | Number of Participants With Dose-Limiting Toxicities (DLTs) | 0 Participants |
| Cohort 5A AdC68 6X10^11 VP + pDNA 5 mg + Treme 40 mg + Sasan 300 mg | Number of Participants With Dose-Limiting Toxicities (DLTs) | 0 Participants |
| Cohort 6A AdC68 6X10^11 VP + pDNA 5 mg + Treme 80 mg + Sasan 300 mg | Number of Participants With Dose-Limiting Toxicities (DLTs) | 0 Participants |
Primary
Number of Participants With Laboratory Abnormalities in Chemistry (Grade 3 or 4)
Chemistry abnormalities (graded per NCI CTCAE v5.0: Grade 3: severe AE; Grade 4: life-threatening consequences, urgent intervention indicated) in at least 1 participant with data in the categories are presented here. Chemistry parameters included aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, sodium, potassium, magnesium, total chloride, total calcium, total bilirubin, blood urea nitrogen (or urea), creatinine, uric acid, glucose (nonfasted), albumin, phosphorous or phosphate, lactate dehydrogenase, lipase, amylase, bicarbonate or carbon dioxide, total protein, TSH (reflex free T4 and free T3).
Time frame: Baseline up to 6 months after EOT (22 months in maximum)
Population: The safety analysis set included all enrolled participants who received at least 1 dose of one of the components of the regimen.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1A Adenovirus C68 (AdC68) 2X10^11 Viral Particles (VP) + Plasmid DNA (pDNA) 5 mg | Number of Participants With Laboratory Abnormalities in Chemistry (Grade 3 or 4) | Blood bilirubin increased | 0 Participants |
| Cohort 1A Adenovirus C68 (AdC68) 2X10^11 Viral Particles (VP) + Plasmid DNA (pDNA) 5 mg | Number of Participants With Laboratory Abnormalities in Chemistry (Grade 3 or 4) | Aspartate aminotransferase increased | 0 Participants |
| Cohort 1A Adenovirus C68 (AdC68) 2X10^11 Viral Particles (VP) + Plasmid DNA (pDNA) 5 mg | Number of Participants With Laboratory Abnormalities in Chemistry (Grade 3 or 4) | Serum amylase increased | 0 Participants |
| Cohort 1A Adenovirus C68 (AdC68) 2X10^11 Viral Particles (VP) + Plasmid DNA (pDNA) 5 mg | Number of Participants With Laboratory Abnormalities in Chemistry (Grade 3 or 4) | Lipase increased | 0 Participants |
| Cohort 1A Adenovirus C68 (AdC68) 2X10^11 Viral Particles (VP) + Plasmid DNA (pDNA) 5 mg | Number of Participants With Laboratory Abnormalities in Chemistry (Grade 3 or 4) | Hypophosphatemia | 0 Participants |
| Cohort 1A Adenovirus C68 (AdC68) 2X10^11 Viral Particles (VP) + Plasmid DNA (pDNA) 5 mg | Number of Participants With Laboratory Abnormalities in Chemistry (Grade 3 or 4) | Hyponatremia | 0 Participants |
| Cohort 1A Adenovirus C68 (AdC68) 2X10^11 Viral Particles (VP) + Plasmid DNA (pDNA) 5 mg | Number of Participants With Laboratory Abnormalities in Chemistry (Grade 3 or 4) | Alkaline phosphatase increased | 0 Participants |
| Cohort 1A Adenovirus C68 (AdC68) 2X10^11 Viral Particles (VP) + Plasmid DNA (pDNA) 5 mg | Number of Participants With Laboratory Abnormalities in Chemistry (Grade 3 or 4) | Alanine aminotransferase increased | 0 Participants |
| Cohort 1A Adenovirus C68 (AdC68) 2X10^11 Viral Particles (VP) + Plasmid DNA (pDNA) 5 mg | Number of Participants With Laboratory Abnormalities in Chemistry (Grade 3 or 4) | Hyperkalemia | 0 Participants |
| Cohort 1A Adenovirus C68 (AdC68) 2X10^11 Viral Particles (VP) + Plasmid DNA (pDNA) 5 mg | Number of Participants With Laboratory Abnormalities in Chemistry (Grade 3 or 4) | Hyperglycemia | 0 Participants |
| Cohort 2A AdC68 6X10^11 VP + pDNA 5 mg | Number of Participants With Laboratory Abnormalities in Chemistry (Grade 3 or 4) | Alkaline phosphatase increased | 0 Participants |
| Cohort 2A AdC68 6X10^11 VP + pDNA 5 mg | Number of Participants With Laboratory Abnormalities in Chemistry (Grade 3 or 4) | Alanine aminotransferase increased | 0 Participants |
| Cohort 2A AdC68 6X10^11 VP + pDNA 5 mg | Number of Participants With Laboratory Abnormalities in Chemistry (Grade 3 or 4) | Aspartate aminotransferase increased | 0 Participants |
| Cohort 2A AdC68 6X10^11 VP + pDNA 5 mg | Number of Participants With Laboratory Abnormalities in Chemistry (Grade 3 or 4) | Blood bilirubin increased | 0 Participants |
| Cohort 2A AdC68 6X10^11 VP + pDNA 5 mg | Number of Participants With Laboratory Abnormalities in Chemistry (Grade 3 or 4) | Hyperglycemia | 1 Participants |
| Cohort 2A AdC68 6X10^11 VP + pDNA 5 mg | Number of Participants With Laboratory Abnormalities in Chemistry (Grade 3 or 4) | Hyperkalemia | 1 Participants |
| Cohort 2A AdC68 6X10^11 VP + pDNA 5 mg | Number of Participants With Laboratory Abnormalities in Chemistry (Grade 3 or 4) | Hyponatremia | 0 Participants |
| Cohort 2A AdC68 6X10^11 VP + pDNA 5 mg | Number of Participants With Laboratory Abnormalities in Chemistry (Grade 3 or 4) | Hypophosphatemia | 2 Participants |
| Cohort 2A AdC68 6X10^11 VP + pDNA 5 mg | Number of Participants With Laboratory Abnormalities in Chemistry (Grade 3 or 4) | Lipase increased | 0 Participants |
| Cohort 2A AdC68 6X10^11 VP + pDNA 5 mg | Number of Participants With Laboratory Abnormalities in Chemistry (Grade 3 or 4) | Serum amylase increased | 0 Participants |
| Cohort 3A AdC68 6X10^11 VP + pDNA 5 mg + Tremelimumab (Treme) 40 mg | Number of Participants With Laboratory Abnormalities in Chemistry (Grade 3 or 4) | Blood bilirubin increased | 0 Participants |
| Cohort 3A AdC68 6X10^11 VP + pDNA 5 mg + Tremelimumab (Treme) 40 mg | Number of Participants With Laboratory Abnormalities in Chemistry (Grade 3 or 4) | Hypophosphatemia | 0 Participants |
| Cohort 3A AdC68 6X10^11 VP + pDNA 5 mg + Tremelimumab (Treme) 40 mg | Number of Participants With Laboratory Abnormalities in Chemistry (Grade 3 or 4) | Alanine aminotransferase increased | 0 Participants |
| Cohort 3A AdC68 6X10^11 VP + pDNA 5 mg + Tremelimumab (Treme) 40 mg | Number of Participants With Laboratory Abnormalities in Chemistry (Grade 3 or 4) | Hyperglycemia | 0 Participants |
| Cohort 3A AdC68 6X10^11 VP + pDNA 5 mg + Tremelimumab (Treme) 40 mg | Number of Participants With Laboratory Abnormalities in Chemistry (Grade 3 or 4) | Aspartate aminotransferase increased | 1 Participants |
| Cohort 3A AdC68 6X10^11 VP + pDNA 5 mg + Tremelimumab (Treme) 40 mg | Number of Participants With Laboratory Abnormalities in Chemistry (Grade 3 or 4) | Alkaline phosphatase increased | 0 Participants |
| Cohort 3A AdC68 6X10^11 VP + pDNA 5 mg + Tremelimumab (Treme) 40 mg | Number of Participants With Laboratory Abnormalities in Chemistry (Grade 3 or 4) | Hyperkalemia | 0 Participants |
| Cohort 3A AdC68 6X10^11 VP + pDNA 5 mg + Tremelimumab (Treme) 40 mg | Number of Participants With Laboratory Abnormalities in Chemistry (Grade 3 or 4) | Lipase increased | 0 Participants |
| Cohort 3A AdC68 6X10^11 VP + pDNA 5 mg + Tremelimumab (Treme) 40 mg | Number of Participants With Laboratory Abnormalities in Chemistry (Grade 3 or 4) | Serum amylase increased | 0 Participants |
| Cohort 3A AdC68 6X10^11 VP + pDNA 5 mg + Tremelimumab (Treme) 40 mg | Number of Participants With Laboratory Abnormalities in Chemistry (Grade 3 or 4) | Hyponatremia | 1 Participants |
| Cohort 4A AdC68 6X10^11 VP + pDNA 5 mg + Treme 40 mg + Sasanlimab (Sasan) 130 mg | Number of Participants With Laboratory Abnormalities in Chemistry (Grade 3 or 4) | Hyponatremia | 1 Participants |
| Cohort 4A AdC68 6X10^11 VP + pDNA 5 mg + Treme 40 mg + Sasanlimab (Sasan) 130 mg | Number of Participants With Laboratory Abnormalities in Chemistry (Grade 3 or 4) | Hypophosphatemia | 0 Participants |
| Cohort 4A AdC68 6X10^11 VP + pDNA 5 mg + Treme 40 mg + Sasanlimab (Sasan) 130 mg | Number of Participants With Laboratory Abnormalities in Chemistry (Grade 3 or 4) | Alkaline phosphatase increased | 1 Participants |
| Cohort 4A AdC68 6X10^11 VP + pDNA 5 mg + Treme 40 mg + Sasanlimab (Sasan) 130 mg | Number of Participants With Laboratory Abnormalities in Chemistry (Grade 3 or 4) | Serum amylase increased | 1 Participants |
| Cohort 4A AdC68 6X10^11 VP + pDNA 5 mg + Treme 40 mg + Sasanlimab (Sasan) 130 mg | Number of Participants With Laboratory Abnormalities in Chemistry (Grade 3 or 4) | Lipase increased | 1 Participants |
| Cohort 4A AdC68 6X10^11 VP + pDNA 5 mg + Treme 40 mg + Sasanlimab (Sasan) 130 mg | Number of Participants With Laboratory Abnormalities in Chemistry (Grade 3 or 4) | Alanine aminotransferase increased | 0 Participants |
| Cohort 4A AdC68 6X10^11 VP + pDNA 5 mg + Treme 40 mg + Sasanlimab (Sasan) 130 mg | Number of Participants With Laboratory Abnormalities in Chemistry (Grade 3 or 4) | Hyperkalemia | 0 Participants |
| Cohort 4A AdC68 6X10^11 VP + pDNA 5 mg + Treme 40 mg + Sasanlimab (Sasan) 130 mg | Number of Participants With Laboratory Abnormalities in Chemistry (Grade 3 or 4) | Hyperglycemia | 0 Participants |
| Cohort 4A AdC68 6X10^11 VP + pDNA 5 mg + Treme 40 mg + Sasanlimab (Sasan) 130 mg | Number of Participants With Laboratory Abnormalities in Chemistry (Grade 3 or 4) | Blood bilirubin increased | 0 Participants |
| Cohort 4A AdC68 6X10^11 VP + pDNA 5 mg + Treme 40 mg + Sasanlimab (Sasan) 130 mg | Number of Participants With Laboratory Abnormalities in Chemistry (Grade 3 or 4) | Aspartate aminotransferase increased | 1 Participants |
| Cohort 5A AdC68 6X10^11 VP + pDNA 5 mg + Treme 40 mg + Sasan 300 mg | Number of Participants With Laboratory Abnormalities in Chemistry (Grade 3 or 4) | Hyponatremia | 0 Participants |
| Cohort 5A AdC68 6X10^11 VP + pDNA 5 mg + Treme 40 mg + Sasan 300 mg | Number of Participants With Laboratory Abnormalities in Chemistry (Grade 3 or 4) | Blood bilirubin increased | 0 Participants |
| Cohort 5A AdC68 6X10^11 VP + pDNA 5 mg + Treme 40 mg + Sasan 300 mg | Number of Participants With Laboratory Abnormalities in Chemistry (Grade 3 or 4) | Hyperglycemia | 2 Participants |
| Cohort 5A AdC68 6X10^11 VP + pDNA 5 mg + Treme 40 mg + Sasan 300 mg | Number of Participants With Laboratory Abnormalities in Chemistry (Grade 3 or 4) | Hyperkalemia | 0 Participants |
| Cohort 5A AdC68 6X10^11 VP + pDNA 5 mg + Treme 40 mg + Sasan 300 mg | Number of Participants With Laboratory Abnormalities in Chemistry (Grade 3 or 4) | Alanine aminotransferase increased | 0 Participants |
| Cohort 5A AdC68 6X10^11 VP + pDNA 5 mg + Treme 40 mg + Sasan 300 mg | Number of Participants With Laboratory Abnormalities in Chemistry (Grade 3 or 4) | Hypophosphatemia | 0 Participants |
| Cohort 5A AdC68 6X10^11 VP + pDNA 5 mg + Treme 40 mg + Sasan 300 mg | Number of Participants With Laboratory Abnormalities in Chemistry (Grade 3 or 4) | Serum amylase increased | 1 Participants |
| Cohort 5A AdC68 6X10^11 VP + pDNA 5 mg + Treme 40 mg + Sasan 300 mg | Number of Participants With Laboratory Abnormalities in Chemistry (Grade 3 or 4) | Lipase increased | 1 Participants |
| Cohort 5A AdC68 6X10^11 VP + pDNA 5 mg + Treme 40 mg + Sasan 300 mg | Number of Participants With Laboratory Abnormalities in Chemistry (Grade 3 or 4) | Aspartate aminotransferase increased | 0 Participants |
| Cohort 5A AdC68 6X10^11 VP + pDNA 5 mg + Treme 40 mg + Sasan 300 mg | Number of Participants With Laboratory Abnormalities in Chemistry (Grade 3 or 4) | Alkaline phosphatase increased | 0 Participants |
| Cohort 6A AdC68 6X10^11 VP + pDNA 5 mg + Treme 80 mg + Sasan 300 mg | Number of Participants With Laboratory Abnormalities in Chemistry (Grade 3 or 4) | Hyperkalemia | 0 Participants |
| Cohort 6A AdC68 6X10^11 VP + pDNA 5 mg + Treme 80 mg + Sasan 300 mg | Number of Participants With Laboratory Abnormalities in Chemistry (Grade 3 or 4) | Serum amylase increased | 0 Participants |
| Cohort 6A AdC68 6X10^11 VP + pDNA 5 mg + Treme 80 mg + Sasan 300 mg | Number of Participants With Laboratory Abnormalities in Chemistry (Grade 3 or 4) | Alkaline phosphatase increased | 0 Participants |
| Cohort 6A AdC68 6X10^11 VP + pDNA 5 mg + Treme 80 mg + Sasan 300 mg | Number of Participants With Laboratory Abnormalities in Chemistry (Grade 3 or 4) | Aspartate aminotransferase increased | 1 Participants |
| Cohort 6A AdC68 6X10^11 VP + pDNA 5 mg + Treme 80 mg + Sasan 300 mg | Number of Participants With Laboratory Abnormalities in Chemistry (Grade 3 or 4) | Hyperglycemia | 0 Participants |
| Cohort 6A AdC68 6X10^11 VP + pDNA 5 mg + Treme 80 mg + Sasan 300 mg | Number of Participants With Laboratory Abnormalities in Chemistry (Grade 3 or 4) | Hyponatremia | 1 Participants |
| Cohort 6A AdC68 6X10^11 VP + pDNA 5 mg + Treme 80 mg + Sasan 300 mg | Number of Participants With Laboratory Abnormalities in Chemistry (Grade 3 or 4) | Blood bilirubin increased | 1 Participants |
| Cohort 6A AdC68 6X10^11 VP + pDNA 5 mg + Treme 80 mg + Sasan 300 mg | Number of Participants With Laboratory Abnormalities in Chemistry (Grade 3 or 4) | Hypophosphatemia | 1 Participants |
| Cohort 6A AdC68 6X10^11 VP + pDNA 5 mg + Treme 80 mg + Sasan 300 mg | Number of Participants With Laboratory Abnormalities in Chemistry (Grade 3 or 4) | Alanine aminotransferase increased | 1 Participants |
| Cohort 6A AdC68 6X10^11 VP + pDNA 5 mg + Treme 80 mg + Sasan 300 mg | Number of Participants With Laboratory Abnormalities in Chemistry (Grade 3 or 4) | Lipase increased | 0 Participants |
Primary
Number of Participants With Laboratory Abnormalities in Hematology and Coagulation (Grade 3 or 4)
Laboratory abnormalities (graded per NCI CTCAE v5.0: Grade 3: severe AE; Grade 4: life-threatening consequences, urgent intervention indicated) in at least 1 participant with data in the categories are presented here. Hematology parameters included hemoglobin, platelets, white blood cell (WBC) count, neutrophils, eosinophils, monocytes, basophils and lymphocytes. Coagulation should include prothrombin time (PT) or international normalized ratio (INR) and activated partial thromboplastin time (APTT).
Time frame: Baseline up to 6 months after EOT (22 months in maximum)
Population: The safety analysis set included all enrolled participants who received at least 1 dose of one of the components of the regimen.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1A Adenovirus C68 (AdC68) 2X10^11 Viral Particles (VP) + Plasmid DNA (pDNA) 5 mg | Number of Participants With Laboratory Abnormalities in Hematology and Coagulation (Grade 3 or 4) | WBC count decreased | 0 Participants |
| Cohort 1A Adenovirus C68 (AdC68) 2X10^11 Viral Particles (VP) + Plasmid DNA (pDNA) 5 mg | Number of Participants With Laboratory Abnormalities in Hematology and Coagulation (Grade 3 or 4) | Lymphocyte count decreased | 0 Participants |
| Cohort 1A Adenovirus C68 (AdC68) 2X10^11 Viral Particles (VP) + Plasmid DNA (pDNA) 5 mg | Number of Participants With Laboratory Abnormalities in Hematology and Coagulation (Grade 3 or 4) | Platelet count decreased | 0 Participants |
| Cohort 1A Adenovirus C68 (AdC68) 2X10^11 Viral Particles (VP) + Plasmid DNA (pDNA) 5 mg | Number of Participants With Laboratory Abnormalities in Hematology and Coagulation (Grade 3 or 4) | APTT prolonged | 0 Participants |
| Cohort 1A Adenovirus C68 (AdC68) 2X10^11 Viral Particles (VP) + Plasmid DNA (pDNA) 5 mg | Number of Participants With Laboratory Abnormalities in Hematology and Coagulation (Grade 3 or 4) | Anemia | 0 Participants |
| Cohort 1A Adenovirus C68 (AdC68) 2X10^11 Viral Particles (VP) + Plasmid DNA (pDNA) 5 mg | Number of Participants With Laboratory Abnormalities in Hematology and Coagulation (Grade 3 or 4) | Neutrophil count decreased | 0 Participants |
| Cohort 2A AdC68 6X10^11 VP + pDNA 5 mg | Number of Participants With Laboratory Abnormalities in Hematology and Coagulation (Grade 3 or 4) | WBC count decreased | 0 Participants |
| Cohort 2A AdC68 6X10^11 VP + pDNA 5 mg | Number of Participants With Laboratory Abnormalities in Hematology and Coagulation (Grade 3 or 4) | APTT prolonged | 0 Participants |
| Cohort 2A AdC68 6X10^11 VP + pDNA 5 mg | Number of Participants With Laboratory Abnormalities in Hematology and Coagulation (Grade 3 or 4) | Lymphocyte count decreased | 0 Participants |
| Cohort 2A AdC68 6X10^11 VP + pDNA 5 mg | Number of Participants With Laboratory Abnormalities in Hematology and Coagulation (Grade 3 or 4) | Anemia | 0 Participants |
| Cohort 2A AdC68 6X10^11 VP + pDNA 5 mg | Number of Participants With Laboratory Abnormalities in Hematology and Coagulation (Grade 3 or 4) | Neutrophil count decreased | 0 Participants |
| Cohort 2A AdC68 6X10^11 VP + pDNA 5 mg | Number of Participants With Laboratory Abnormalities in Hematology and Coagulation (Grade 3 or 4) | Platelet count decreased | 0 Participants |
| Cohort 3A AdC68 6X10^11 VP + pDNA 5 mg + Tremelimumab (Treme) 40 mg | Number of Participants With Laboratory Abnormalities in Hematology and Coagulation (Grade 3 or 4) | Lymphocyte count decreased | 1 Participants |
| Cohort 3A AdC68 6X10^11 VP + pDNA 5 mg + Tremelimumab (Treme) 40 mg | Number of Participants With Laboratory Abnormalities in Hematology and Coagulation (Grade 3 or 4) | WBC count decreased | 0 Participants |
| Cohort 3A AdC68 6X10^11 VP + pDNA 5 mg + Tremelimumab (Treme) 40 mg | Number of Participants With Laboratory Abnormalities in Hematology and Coagulation (Grade 3 or 4) | Anemia | 2 Participants |
| Cohort 3A AdC68 6X10^11 VP + pDNA 5 mg + Tremelimumab (Treme) 40 mg | Number of Participants With Laboratory Abnormalities in Hematology and Coagulation (Grade 3 or 4) | APTT prolonged | 1 Participants |
| Cohort 3A AdC68 6X10^11 VP + pDNA 5 mg + Tremelimumab (Treme) 40 mg | Number of Participants With Laboratory Abnormalities in Hematology and Coagulation (Grade 3 or 4) | Neutrophil count decreased | 0 Participants |
| Cohort 3A AdC68 6X10^11 VP + pDNA 5 mg + Tremelimumab (Treme) 40 mg | Number of Participants With Laboratory Abnormalities in Hematology and Coagulation (Grade 3 or 4) | Platelet count decreased | 1 Participants |
| Cohort 4A AdC68 6X10^11 VP + pDNA 5 mg + Treme 40 mg + Sasanlimab (Sasan) 130 mg | Number of Participants With Laboratory Abnormalities in Hematology and Coagulation (Grade 3 or 4) | Platelet count decreased | 0 Participants |
| Cohort 4A AdC68 6X10^11 VP + pDNA 5 mg + Treme 40 mg + Sasanlimab (Sasan) 130 mg | Number of Participants With Laboratory Abnormalities in Hematology and Coagulation (Grade 3 or 4) | Anemia | 0 Participants |
| Cohort 4A AdC68 6X10^11 VP + pDNA 5 mg + Treme 40 mg + Sasanlimab (Sasan) 130 mg | Number of Participants With Laboratory Abnormalities in Hematology and Coagulation (Grade 3 or 4) | Neutrophil count decreased | 0 Participants |
| Cohort 4A AdC68 6X10^11 VP + pDNA 5 mg + Treme 40 mg + Sasanlimab (Sasan) 130 mg | Number of Participants With Laboratory Abnormalities in Hematology and Coagulation (Grade 3 or 4) | APTT prolonged | 1 Participants |
| Cohort 4A AdC68 6X10^11 VP + pDNA 5 mg + Treme 40 mg + Sasanlimab (Sasan) 130 mg | Number of Participants With Laboratory Abnormalities in Hematology and Coagulation (Grade 3 or 4) | WBC count decreased | 0 Participants |
| Cohort 4A AdC68 6X10^11 VP + pDNA 5 mg + Treme 40 mg + Sasanlimab (Sasan) 130 mg | Number of Participants With Laboratory Abnormalities in Hematology and Coagulation (Grade 3 or 4) | Lymphocyte count decreased | 0 Participants |
| Cohort 5A AdC68 6X10^11 VP + pDNA 5 mg + Treme 40 mg + Sasan 300 mg | Number of Participants With Laboratory Abnormalities in Hematology and Coagulation (Grade 3 or 4) | Anemia | 0 Participants |
| Cohort 5A AdC68 6X10^11 VP + pDNA 5 mg + Treme 40 mg + Sasan 300 mg | Number of Participants With Laboratory Abnormalities in Hematology and Coagulation (Grade 3 or 4) | Lymphocyte count decreased | 0 Participants |
| Cohort 5A AdC68 6X10^11 VP + pDNA 5 mg + Treme 40 mg + Sasan 300 mg | Number of Participants With Laboratory Abnormalities in Hematology and Coagulation (Grade 3 or 4) | WBC count decreased | 1 Participants |
| Cohort 5A AdC68 6X10^11 VP + pDNA 5 mg + Treme 40 mg + Sasan 300 mg | Number of Participants With Laboratory Abnormalities in Hematology and Coagulation (Grade 3 or 4) | Platelet count decreased | 0 Participants |
| Cohort 5A AdC68 6X10^11 VP + pDNA 5 mg + Treme 40 mg + Sasan 300 mg | Number of Participants With Laboratory Abnormalities in Hematology and Coagulation (Grade 3 or 4) | APTT prolonged | 1 Participants |
| Cohort 5A AdC68 6X10^11 VP + pDNA 5 mg + Treme 40 mg + Sasan 300 mg | Number of Participants With Laboratory Abnormalities in Hematology and Coagulation (Grade 3 or 4) | Neutrophil count decreased | 2 Participants |
| Cohort 6A AdC68 6X10^11 VP + pDNA 5 mg + Treme 80 mg + Sasan 300 mg | Number of Participants With Laboratory Abnormalities in Hematology and Coagulation (Grade 3 or 4) | WBC count decreased | 0 Participants |
| Cohort 6A AdC68 6X10^11 VP + pDNA 5 mg + Treme 80 mg + Sasan 300 mg | Number of Participants With Laboratory Abnormalities in Hematology and Coagulation (Grade 3 or 4) | APTT prolonged | 1 Participants |
| Cohort 6A AdC68 6X10^11 VP + pDNA 5 mg + Treme 80 mg + Sasan 300 mg | Number of Participants With Laboratory Abnormalities in Hematology and Coagulation (Grade 3 or 4) | Anemia | 0 Participants |
| Cohort 6A AdC68 6X10^11 VP + pDNA 5 mg + Treme 80 mg + Sasan 300 mg | Number of Participants With Laboratory Abnormalities in Hematology and Coagulation (Grade 3 or 4) | Lymphocyte count decreased | 3 Participants |
| Cohort 6A AdC68 6X10^11 VP + pDNA 5 mg + Treme 80 mg + Sasan 300 mg | Number of Participants With Laboratory Abnormalities in Hematology and Coagulation (Grade 3 or 4) | Neutrophil count decreased | 0 Participants |
| Cohort 6A AdC68 6X10^11 VP + pDNA 5 mg + Treme 80 mg + Sasan 300 mg | Number of Participants With Laboratory Abnormalities in Hematology and Coagulation (Grade 3 or 4) | Platelet count decreased | 0 Participants |
Primary
Number of Participants With Laboratory Abnormalities in Urinalysis (Grade 3 or 4)
Urinalysis abnormalities (graded per NCI CTCAE v5.0: Grade 3: severe AE; Grade 4: life-threatening consequences, urgent intervention indicated) in at least 1 participant with data in the categories are presented here. Urine parameters included urine protein and urine blood.
Time frame: Baseline up to 6 months after EOT (22 months in maximum)
Population: The safety analysis set included all enrolled participants who received at least 1 dose of one of the components of the regimen.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1A Adenovirus C68 (AdC68) 2X10^11 Viral Particles (VP) + Plasmid DNA (pDNA) 5 mg | Number of Participants With Laboratory Abnormalities in Urinalysis (Grade 3 or 4) | 0 Participants |
| Cohort 2A AdC68 6X10^11 VP + pDNA 5 mg | Number of Participants With Laboratory Abnormalities in Urinalysis (Grade 3 or 4) | 0 Participants |
| Cohort 3A AdC68 6X10^11 VP + pDNA 5 mg + Tremelimumab (Treme) 40 mg | Number of Participants With Laboratory Abnormalities in Urinalysis (Grade 3 or 4) | 0 Participants |
| Cohort 4A AdC68 6X10^11 VP + pDNA 5 mg + Treme 40 mg + Sasanlimab (Sasan) 130 mg | Number of Participants With Laboratory Abnormalities in Urinalysis (Grade 3 or 4) | 0 Participants |
| Cohort 5A AdC68 6X10^11 VP + pDNA 5 mg + Treme 40 mg + Sasan 300 mg | Number of Participants With Laboratory Abnormalities in Urinalysis (Grade 3 or 4) | 0 Participants |
| Cohort 6A AdC68 6X10^11 VP + pDNA 5 mg + Treme 80 mg + Sasan 300 mg | Number of Participants With Laboratory Abnormalities in Urinalysis (Grade 3 or 4) | 0 Participants |
Primary
Proportion of Participants Who Achieved Complete Response, Partial Response or Stable Disease for More Than 6 Months Using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 Criteria (Part 2)
Clinical Benefit Rate (CBR) is defined as the proportion of participants who achieved anti-tumor responses of Complete Response (CR), Partial Response (PR), or Stable Disease (SD) for \>6 months. CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All target nodes must decrease to normal size (short axis \<10 mm). All target lesions must be assessed. PR was defined as ≥30% decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease and no new lesions. All target lesions must be assessed. SD: Does not qualify for CR, PR or Progression. SD can follow PR only in the rare case that the sum increases by \<20% from the nadir, but enough that a previously documented 30% decrease no longer holds.
Time frame: Performed every 8 weeks from baseline up to Week 32
Population: All enrolled participants who received at least 1 dose of all regimen components administered on Cycle 1 Day 1 and must at least 1 valid and determinate assay result related to the proposed analysis. This was a primary endpoint of Part 2. Part 2 of the study was never opened as the study terminated.
Secondary
Area Under the Curve From Time 0 Extrapolated to Infinity (AUCinf) of Sasanlimab
AUCinf was defined as area under the concentration time curve from time 0 extrapolated to infinity. AUCinf of sasanlimab was not reported due to the limited data points during elimination phase, and the lack of a well-characterized terminal phase. A well-characterized terminal phase was defined as one with at least 3 data points, r\^2 ≥0.9, and percent of AUCextrap% ≤20%.
Time frame: Cycle 1: at pre-dose on Days 1, 3-6, 8, 15, 22, 29, 57, 85; Cycle 2: at pre-dose on Day 1 and Day 29; EOT; Months 2, 4 and 6 after EOT visit
Population: According to PK analysis reporting defined in protocol, the concentration-time data of sasan after the 1st dose were analyzed individually by noncompartmental methods to determine PK parameters for participants in Cohorts 4A and 5A. Sasan PK parameters in Cohort 6A were not calculated because by design only sparse PK samples were collected. Cohorts 1A, 2A and 3A were not included in the analysis since sasan was not administered in those cohorts.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Cohort 1A Adenovirus C68 (AdC68) 2X10^11 Viral Particles (VP) + Plasmid DNA (pDNA) 5 mg | Area Under the Curve From Time 0 Extrapolated to Infinity (AUCinf) of Sasanlimab | NA ng*hr/mL |
| Cohort 2A AdC68 6X10^11 VP + pDNA 5 mg | Area Under the Curve From Time 0 Extrapolated to Infinity (AUCinf) of Sasanlimab | NA ng*hr/mL |
Secondary
AUCinf of Tremelimumab
AUCinf was defined as area under the concentration time curve from time 0 extrapolated to infinity. AUCinf of tremelimumab was not reported due to the limited data points during elimination phase, and the lack of a well-characterized terminal phase. A well-characterized terminal phase was defined as one with at least 3 data points, r\^2 ≥0.9, and percent of AUCextrap% ≤20%.
Time frame: Cycle 1: at pre-dose on Days 1, 3-6, 8, 15, 22, 29, 57, 85; Cycle 2: at pre-dose on Day 1 and Day 29; EOT; Months 2, 4 and 6 after EOT visit
Population: According to PK analysis reporting defined in protocol, the concentration-time data of treme after the 1st dose were analyzed individually by noncompartmental methods to determine PK parameters for participants in Cohorts 3A and 6A. Treme PK parameters in Cohort 4A and 5A were not calculated because only sparse PK samples were collected. Cohorts 1A and 2A were not included in the analysis since treme was not administered in those cohorts.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Cohort 1A Adenovirus C68 (AdC68) 2X10^11 Viral Particles (VP) + Plasmid DNA (pDNA) 5 mg | AUCinf of Tremelimumab | NA ng*hr/mL |
| Cohort 2A AdC68 6X10^11 VP + pDNA 5 mg | AUCinf of Tremelimumab | NA ng*hr/mL |
Secondary
Cmax of Tremelimumab
Cmax was defined as the maximum observed serum concentration.
Time frame: Cycle 1: at pre-dose on Days 1, 3-6, 8, 15, 22, 29, 57, 85; Cycle 2: at pre-dose on Day 1 and Day 29; EOT; Months 2, 4 and 6 after EOT visit
Population: According to PK analysis reporting defined in protocol, the concentration-time data of treme after the 1st dose were analyzed individually by noncompartmental methods to determine PK parameters for participants in Cohorts 3A and 6A. Treme PK parameters in Cohort 4A and 5A were not calculated because only sparse PK samples were collected. Cohorts 1A and 2A were not included in the analysis since treme was not administered in those cohorts.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1A Adenovirus C68 (AdC68) 2X10^11 Viral Particles (VP) + Plasmid DNA (pDNA) 5 mg | Cmax of Tremelimumab | 1692 ng/mL | Geometric Coefficient of Variation 47 |
| Cohort 2A AdC68 6X10^11 VP + pDNA 5 mg | Cmax of Tremelimumab | 4550 ng/mL | Geometric Coefficient of Variation 62 |
Secondary
Ctrough of Tremelimumab
Ctrough was defined as the drug concentration observed at the last planned timepoint prior to dosing.
Time frame: Cycle 1: at pre-dose on Days 1, 3-6, 8, 15, 22, 29, 57, 85; Cycle 2: at pre-dose on Day 1
Population: According to PK analysis reporting defined in protocol, the concentration-time data of treme after the 1st dose were analyzed individually by noncompartmental methods to determine PK parameters for participants in Cohorts 3A and 6A. Treme PK parameters in Cohort 4A and 5A were not calculated because only sparse PK samples were collected. Cohorts 1A and 2A were not included in the analysis since treme was not administered in those cohorts.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Cohort 1A Adenovirus C68 (AdC68) 2X10^11 Viral Particles (VP) + Plasmid DNA (pDNA) 5 mg | Ctrough of Tremelimumab | NA ng/mL |
| Cohort 2A AdC68 6X10^11 VP + pDNA 5 mg | Ctrough of Tremelimumab | NA ng/mL |
Secondary
Maximum Observed Serum Concentration (Cmax) of Sasanlimab
Cmax was defined as the maximum observed serum concentration.
Time frame: Cycle 1: at pre-dose on Days 1, 3-6, 8, 15, 22, 29, 57, 85; Cycle 2: at pre-dose on Day 1 and Day 29; EOT; Months 2, 4, and 6 after EOT visit
Population: According to PK analysis reporting defined in protocol, the concentration-time data of sasan after the 1st dose were analyzed individually by noncompartmental methods to determine PK parameters for participants in Cohorts 4A and 5A. Sasan PK parameters in Cohort 6A were not calculated because by design only sparse PK samples were collected. Cohorts 1A, 2A and 3A were not included in the analysis since sasan was not administered in those cohorts.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1A Adenovirus C68 (AdC68) 2X10^11 Viral Particles (VP) + Plasmid DNA (pDNA) 5 mg | Maximum Observed Serum Concentration (Cmax) of Sasanlimab | 10520 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 46 |
| Cohort 2A AdC68 6X10^11 VP + pDNA 5 mg | Maximum Observed Serum Concentration (Cmax) of Sasanlimab | 15640 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 82 |
Secondary
Number of Participants With ADA Against Tremelimumab
Participants were considered ADA-positive if (1) baseline titer was missing or negative and participant had ≥1 post-treatment positive titer (treatment-induced), or (2) positive titer at baseline and had a ratio of ≥4 in titer (dilution) to baseline in ≥1 post-treatment sample (treatment-boosted).
Time frame: Cycle 1: on Day 1, Day 29, and Day 85; Cycle 2: on Day 29; at the EOT visit, and 2, 4 and 6 months after EOT. Samples collected on dosing days were obtained within 6 hours prior to tremelimumab dosing.
Population: All enrolled participants who received at least 1 dose of the VBIR-2 component was the participant of the immunogenicity assessment (tremelimumab or sasanlimab). For this outcome measure, participants who received tremelimumab in Cohorts 3A, 4A, 5A and 6A were included.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1A Adenovirus C68 (AdC68) 2X10^11 Viral Particles (VP) + Plasmid DNA (pDNA) 5 mg | Number of Participants With ADA Against Tremelimumab | Treatment-induced | 0 Participants |
| Cohort 1A Adenovirus C68 (AdC68) 2X10^11 Viral Particles (VP) + Plasmid DNA (pDNA) 5 mg | Number of Participants With ADA Against Tremelimumab | Treatment-boosted | 0 Participants |
| Cohort 2A AdC68 6X10^11 VP + pDNA 5 mg | Number of Participants With ADA Against Tremelimumab | Treatment-boosted | 0 Participants |
| Cohort 2A AdC68 6X10^11 VP + pDNA 5 mg | Number of Participants With ADA Against Tremelimumab | Treatment-induced | 0 Participants |
| Cohort 3A AdC68 6X10^11 VP + pDNA 5 mg + Tremelimumab (Treme) 40 mg | Number of Participants With ADA Against Tremelimumab | Treatment-induced | 0 Participants |
| Cohort 3A AdC68 6X10^11 VP + pDNA 5 mg + Tremelimumab (Treme) 40 mg | Number of Participants With ADA Against Tremelimumab | Treatment-boosted | 0 Participants |
| Cohort 4A AdC68 6X10^11 VP + pDNA 5 mg + Treme 40 mg + Sasanlimab (Sasan) 130 mg | Number of Participants With ADA Against Tremelimumab | Treatment-induced | 1 Participants |
| Cohort 4A AdC68 6X10^11 VP + pDNA 5 mg + Treme 40 mg + Sasanlimab (Sasan) 130 mg | Number of Participants With ADA Against Tremelimumab | Treatment-boosted | 0 Participants |
Secondary
Number of Participants With Anti-Drug Antibody (ADA) Against Sasanlimab
Participants were considered ADA-positive if (1) baseline titer was missing or negative and participant had ≥1 post-treatment positive titer (treatment-induced), or (2) positive titer at baseline and had a ratio of ≥4 in titer (dilution) to baseline in ≥1 post-treatment sample (treatment-boosted).
Time frame: Cycle 1: on Day 1, Day 29, and Day 85; Cycle 2: on Day 29; at the EOT visit, and 2, 4 and 6 months after EOT. Samples to be collected on dosing days were obtained within 6 hours prior to sasanlimab dosing.
Population: All enrolled participants who received at least 1 dose of the VBIR-2 component was the participant of the immunogenicity assessment (tremelimumab or sasanlimab). For this outcome measure, participants who received sasanlimab in Cohorts 4A, 5A and 6A were included.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1A Adenovirus C68 (AdC68) 2X10^11 Viral Particles (VP) + Plasmid DNA (pDNA) 5 mg | Number of Participants With Anti-Drug Antibody (ADA) Against Sasanlimab | Treatment-induced | 0 Participants |
| Cohort 1A Adenovirus C68 (AdC68) 2X10^11 Viral Particles (VP) + Plasmid DNA (pDNA) 5 mg | Number of Participants With Anti-Drug Antibody (ADA) Against Sasanlimab | Treatment-boosted | 0 Participants |
| Cohort 2A AdC68 6X10^11 VP + pDNA 5 mg | Number of Participants With Anti-Drug Antibody (ADA) Against Sasanlimab | Treatment-induced | 0 Participants |
| Cohort 2A AdC68 6X10^11 VP + pDNA 5 mg | Number of Participants With Anti-Drug Antibody (ADA) Against Sasanlimab | Treatment-boosted | 0 Participants |
| Cohort 3A AdC68 6X10^11 VP + pDNA 5 mg + Tremelimumab (Treme) 40 mg | Number of Participants With Anti-Drug Antibody (ADA) Against Sasanlimab | Treatment-induced | 0 Participants |
| Cohort 3A AdC68 6X10^11 VP + pDNA 5 mg + Tremelimumab (Treme) 40 mg | Number of Participants With Anti-Drug Antibody (ADA) Against Sasanlimab | Treatment-boosted | 0 Participants |
Secondary
Number of Participants With NAb Against Tremelimumab
A participant was NAb positive if (1) baseline titer was missing or negative and participant had ≥1 post-treatment positive titer (treatment-induced), or (2) positive titer at baseline and had a ratio of ≥4 in titer (dilution) to baseline in ≥1 post-treatment sample (treatment-boosted). Participants who were either (1) an ADA-negative participant or (2) an ADA-positive participant without treatment-induced or treatment-boosted NAb response were considered as NAb negative. NAb evaluation was not considered as meaningful taken that treatment-induced ADA was found in only 1 participant. Thus, NAb to tremelimumab was not examined.
Time frame: Cycle 1: on Day 1, Day 29, and Day 85; Cycle 2: on Day 29; at the EOT visit, and 2, 4 and 6 months after EOT. Samples to be collected on dosing days were obtained within 6 hours prior to tremelimumab dosing.
Population: All enrolled participants who received at least 1 dose of all assigned regimen components administered, and must have had at least 1 valid and determinate assay result related to the proposed analysis.
Secondary
Number of Participants With Neutralizing Antibody (NAb) Against Sasanlimab
A participant was NAb positive if (1) baseline titer was missing or negative and participant had ≥1 post-treatment positive titer (treatment-induced), or (2) positive titer at baseline and had a ratio of ≥4 in titer (dilution) to baseline in ≥1 post-treatment sample (treatment-boosted). Participants who were either (1) an ADA-negative participant or (2) an ADA-positive participant without treatment-induced or treatment-boosted NAb response were considered as NAb negative.
Time frame: Cycle 1: on Day 1, Day 29, and Day 85; Cycle 2: on Day 29; at the EOT visit, and 2, 4 and 6 months after EOT. Samples to be collected on dosing days were obtained within 6 hours prior to sasanlimab dosing.
Population: All enrolled participants who received at least 1 dose of all assigned regimen components administered, and must have had at least 1 valid and determinate assay result related to the proposed analysis. For this outcome measure, NAb against sasanlimab was examined for the 2 participants with ADA positive samples at baseline in Cohort 6A.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 3A AdC68 6X10^11 VP + pDNA 5 mg + Tremelimumab (Treme) 40 mg | Number of Participants With Neutralizing Antibody (NAb) Against Sasanlimab | 0 Participants |
Secondary
Objective Response Rate (ORR) Using RECIST v1.1
ORR was defined as the percentage of participants with best overall response based assessment of CR or PR according to RECIST v1.1. Per RECIST v1.1: CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All target nodes must decrease to normal size (short axis \<10 mm). All target lesions must be assessed. PR was defined as ≥30% decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease and no new lesions. All target lesions must be assessed.
Time frame: Performed every 8 weeks from baseline up to Week 32
Population: All enrolled participants who received at least 1 dose of all regimen components administered on Cycle 1 Day 1 and must at least 1 valid and determinate assay result related to the proposed analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1A Adenovirus C68 (AdC68) 2X10^11 Viral Particles (VP) + Plasmid DNA (pDNA) 5 mg | Objective Response Rate (ORR) Using RECIST v1.1 | 0 Percentage of participants |
| Cohort 2A AdC68 6X10^11 VP + pDNA 5 mg | Objective Response Rate (ORR) Using RECIST v1.1 | 0 Percentage of participants |
| Cohort 3A AdC68 6X10^11 VP + pDNA 5 mg + Tremelimumab (Treme) 40 mg | Objective Response Rate (ORR) Using RECIST v1.1 | 0 Percentage of participants |
| Cohort 4A AdC68 6X10^11 VP + pDNA 5 mg + Treme 40 mg + Sasanlimab (Sasan) 130 mg | Objective Response Rate (ORR) Using RECIST v1.1 | 0 Percentage of participants |
| Cohort 5A AdC68 6X10^11 VP + pDNA 5 mg + Treme 40 mg + Sasan 300 mg | Objective Response Rate (ORR) Using RECIST v1.1 | 0 Percentage of participants |
| Cohort 6A AdC68 6X10^11 VP + pDNA 5 mg + Treme 80 mg + Sasan 300 mg | Objective Response Rate (ORR) Using RECIST v1.1 | 0 Percentage of participants |
Secondary
PFS Using RECIST v1.1 With TNBC
PFS was defined as the time from start date to date of first documentation of progression, or death due to any cause. Progression was defined as the appearance of local, regional or distant disease of the same type after complete response or progression of pre existing lesions.
Time frame: Performed every 3 weeks after treatment discontinuation until death, participant refusal, or lost to follow-up (telephone contact acceptable).
Population: All enrolled participants with TNBC who received at least 1 dose of all regimen components administered on Cycle 1 Day 1 and must at least 1 valid and determinate assay result related to the proposed analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1A Adenovirus C68 (AdC68) 2X10^11 Viral Particles (VP) + Plasmid DNA (pDNA) 5 mg | PFS Using RECIST v1.1 With TNBC | 1.2 Months |
| Cohort 2A AdC68 6X10^11 VP + pDNA 5 mg | PFS Using RECIST v1.1 With TNBC | 7.0 Months |
| Cohort 3A AdC68 6X10^11 VP + pDNA 5 mg + Tremelimumab (Treme) 40 mg | PFS Using RECIST v1.1 With TNBC | 1.3 Months |
| Cohort 4A AdC68 6X10^11 VP + pDNA 5 mg + Treme 40 mg + Sasanlimab (Sasan) 130 mg | PFS Using RECIST v1.1 With TNBC | 1.9 Months |
| Cohort 5A AdC68 6X10^11 VP + pDNA 5 mg + Treme 40 mg + Sasan 300 mg | PFS Using RECIST v1.1 With TNBC | 1.8 Months |
Secondary
Progression-Free Survival (PFS) Using RECIST v1.1 With NSCLC
PFS was defined as the time from start date to date of first documentation of progression, or death due to any cause. Progression was defined as the appearance of local, regional or distant disease of the same type after complete response or progression of pre-existing lesions.
Time frame: Performed every 3 weeks after treatment discontinuation until death, participant refusal, or lost to follow-up (telephone contact acceptable).
Population: All enrolled participants with NSCLC who received at least 1 dose of all regimen components administered on Cycle 1 Day 1 and must at least 1 valid and determinate assay result related to the proposed analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1A Adenovirus C68 (AdC68) 2X10^11 Viral Particles (VP) + Plasmid DNA (pDNA) 5 mg | Progression-Free Survival (PFS) Using RECIST v1.1 With NSCLC | 2.0 Months |
| Cohort 2A AdC68 6X10^11 VP + pDNA 5 mg | Progression-Free Survival (PFS) Using RECIST v1.1 With NSCLC | 1.8 Months |
| Cohort 3A AdC68 6X10^11 VP + pDNA 5 mg + Tremelimumab (Treme) 40 mg | Progression-Free Survival (PFS) Using RECIST v1.1 With NSCLC | 1.8 Months |
| Cohort 4A AdC68 6X10^11 VP + pDNA 5 mg + Treme 40 mg + Sasanlimab (Sasan) 130 mg | Progression-Free Survival (PFS) Using RECIST v1.1 With NSCLC | 1.8 Months |
Secondary
Time to Maximum Concentration (Tmax) of Sasanlimab
Tmax was defined as the time to reach maximum observed serum concentration.
Time frame: Cycle 1: at pre-dose on Days 1, 3-6, 8, 15, 22, 29, 57, 85; Cycle 2: at pre-dose on Day 1 and Day 29; EOT; Months 2, 4 and 6 after EOT visit
Population: According to PK analysis reporting defined in protocol, the concentration-time data of sasan after the 1st dose were analyzed individually by noncompartmental methods to determine PK parameters for participants in Cohorts 4A and 5A. Sasan PK parameters in Cohort 6A were not calculated because by design only sparse PK samples were collected. Cohorts 1A, 2A and 3A were not included in the analysis since sasan was not administered in those cohorts.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1A Adenovirus C68 (AdC68) 2X10^11 Viral Particles (VP) + Plasmid DNA (pDNA) 5 mg | Time to Maximum Concentration (Tmax) of Sasanlimab | 165.0 Hour |
| Cohort 2A AdC68 6X10^11 VP + pDNA 5 mg | Time to Maximum Concentration (Tmax) of Sasanlimab | 251.5 Hour |
Secondary
Titers of Treatment-Induced ADA and NAb Against Sasanlimab
Titers were measured in terms of 1/dilution. Only the samples tested positive for ADA were to be further tested for Nab. Treatment-induced ADA: baseline titer is missing or negative and participant has \>= 1 post-treatment positive titer. Treatment-induced NAb: baseline titer was missing or negative and participant had ≥1 post-treatment positive titer.
Time frame: Cycle 1: at Day 1, Day 29, and Day 85; Cycle 2: at Day 29; at the EOT visit, and 2, 4 and 6 months after EOT. Samples to be collected on dosing days were obtained within 6 hours prior to sasanlimab dosing.
Population: All enrolled participants who received at least 1 dose of all assigned regimen components administered, and must have had at least 1 valid and determinate assay result related to the proposed analysis. For this outcome measure, participants who received sasanlimab in Cohorts 4A, 5A and 6A were included. No participants had treatment-induced ADA.
| Arm | Measure | Group | Value |
|---|---|---|---|
| Unknown | Titers of Treatment-Induced ADA and NAb Against Sasanlimab | ADA Titer | — |
| Unknown | Titers of Treatment-Induced ADA and NAb Against Sasanlimab | NAb Titer | — |
Secondary
Titers of Treatment-Induced ADA and NAb Against Tremelimumab
Titers were measured in terms of 1/dilution. Only the samples tested positive for ADA were to be further tested for Nab. Treatment-induced ADA: baseline titer is missing or negative and participant has \>= 1 post-treatment positive titer. Treatment-induced NAb: baseline titer was missing or negative and participant had ≥1 post-treatment positive titer. NAb was not examined as the evaluation was not meaningful considering only 1 participant had treatment-induced ADA.
Time frame: Cycle 1: at Day 1, Day 29, and Day 85; Cycle 2: at Day 29; at the EOT visit, and 2, 4 and 6 months after EOT. Samples to be collected on dosing days were obtained within 6 hours prior to tremelimumab dosing.
Population: All enrolled participants who received at least 1 dose of all assigned regimen components administered, and must have had at least 1 valid and determinate assay result related to the proposed analysis.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort 4A AdC68 6X10^11 VP + pDNA 5 mg + Treme 40 mg + Sasanlimab (Sasan) 130 mg | Titers of Treatment-Induced ADA and NAb Against Tremelimumab | ADA Titer | NA 1/dilution |
Secondary
Tmax of Tremelimumab
Tmax was defined as the time to reach maximum observed serum concentration.
Time frame: Cycle 1: at pre-dose on Days 1, 3-6, 8, 15, 22, 29, 57, 85; Cycle 2: at pre-dose on Day 1 and Day 29; EOT; Months 2, 4 and 6 after EOT visit
Population: According to PK analysis reporting defined in protocol, the concentration-time data of treme after the 1st dose were analyzed individually by noncompartmental methods to determine PK parameters for participants in Cohorts 3A and 6A. Treme PK parameters in Cohort 4A and 5A were not calculated because only sparse PK samples were collected. Cohorts 1A and 2A were not included in the analysis since treme was not administered in those cohorts.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1A Adenovirus C68 (AdC68) 2X10^11 Viral Particles (VP) + Plasmid DNA (pDNA) 5 mg | Tmax of Tremelimumab | 284.0 Hour |
| Cohort 2A AdC68 6X10^11 VP + pDNA 5 mg | Tmax of Tremelimumab | 166.0 Hour |
Secondary
Trough Concentrations After Multiple Dosing (Ctrough) of Sasanlimab
Ctrough was defined as the drug concentration observed at the last planned timepoint prior to dosing. Ctrough was not calculated for sasanlimab because trough concentration prior to the fifth dose (on Cycle 2 Day 1) were not collected for any participants in Cohorts 4A or 5A.
Time frame: Cycle 1: at pre-dose on Days 1, 3-6, 8, 15, 22, 29, 57, 85; Cycle 2: at pre-dose on Day 1 and Day 29; Months 2, 4, 6 after EOT visit
Population: According to PK analysis reporting defined in protocol, the concentration-time data of sasan after the 1st dose were analyzed individually by noncompartmental methods to determine PK parameters for participants in Cohorts 4A and 5A. Sasan PK parameters in Cohort 6A were not calculated because by design only sparse PK samples were collected. Cohorts 1A, 2A and 3A were not included in the analysis since sasan was not administered in those cohorts.