Solid Tumors
Conditions
Brief summary
The goal of this trial is to learn about the antibody acasunlimab (an antibody also known as GEN1046) when it is used alone and when it is used together with standard of care treatment (docetaxel) or another antibody cancer drug, pembrolizumab (with or without chemotherapy), for treatment of patients with certain types of cancer. All subjects will receive active drug; no one will receive placebo. This trial has 2 parts. The purpose of the first part is to find out if acasunlimab at various doses is safe and to find out the best doses of acasunlimab to use. The purpose of the second part is to give acasunlimab to more subjects to see how well the doses of acasunlimab selected in the first part work against cancer when given alone and how well they work when given with pembrolizumab with or without chemotherapy. Trial details include: * The average trial duration for an individual subject will be about 74 weeks. * The average treatment duration for an individual subject will be about 21 weeks. * The visit frequency will be weekly at first and lessening over time until visits are only once every 3 weeks.
Detailed description
The trial is an open-label, multi-center safety trial of acasunlimab (GEN1046). The trial consists of 2 consecutive parts: a first-in-human (FIH) dose escalation (phase 1) and an expansion (phase 2a). The expansion part of the trial will be initiated once the Recommended Phase 2 Dose (RP2D) has been determined.
Interventions
BIOLOGICALAcasunlimab
Acasunlimab will be administered intravenously once every 21 days (in selected expansion cohorts acasunlimab will be administered intravenously once every 21 days for the first 2 cycles, and every 42 days in subsequent cycles).
BIOLOGICALAcasunlimab in combination with docetaxel (in a single expansion cohort)
Acasunlimab and docetaxel will be administered intravenously once every 21 days.
BIOLOGICALAcasunlimab in combination with pembrolizumab (in a separate expansion cohort)
Acasunlimab and pembrolizumab will be administered intravenously once every 21 days or every 42 days, respectively.
BIOLOGICALAcasunlimab in combination with pembrolizumab and standard chemotherapy (in separate expansion cohorts)
Acasunlimab and pembrolizumab and standard chemotherapy will be administered intravenously once every 21 days for 4 cycles, followed by treatment with acasunlimab and pembrolizumab once every 21 days.
Sponsors
Genmab
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: For Dose Escalation: • Have a histologically or cytologically confirmed non-CNS solid tumor that is metastatic or unresectable and for whom there is no available standard therapy For Expansion: • Have histologically or cytological confirmed diagnosis of relapsed or refractory, advanced and/or metastatic NSCLC, EC, UC, TNBC, SCCHN, or cervical cancer who are not anymore candidates for standard therapy For separate expansion cohorts: metastatic NSCLC without prior systemic treatment regimens for metastatic disease. For Both Dose Escalation and Expansion * Have measurable disease according to RECIST 1.1 * Have Eastern Cooperative Oncology Group (ECOG) 0-1 * Have an acceptable hematological status * Have acceptable liver function * Have an acceptable coagulation status * Have acceptable renal function Key
Exclusion criteria
* Have uncontrolled intercurrent illness, including but not limited to: * Ongoing or active infection requiring intravenous treatment with anti-infective therapy, or any ongoing systemic inflammatory condition requiring further diagnostic work-up or management during screening. * Symptomatic congestive heart failure (Grade III or IV as classified by the New York Heart Association), unstable angina pectoris or cardiac arrhythmia * Uncontrolled hypertension defined as systolic blood pressure ≥ 160 mmHg and/or diastolic blood pressure ≥ 100 mmHg, despite optimal medical management * Ongoing or recent evidence of autoimmune disease * History of irAEs that led to prior checkpoint treatment discontinuation * Prior history of myositis, Guillain-Barré syndrome, or myasthenia gravis of any grade * History of chronic liver disease or evidence of hepatic cirrhosis * History of non-infectious pneumonitis that has required steroids or currently has pneumonitis * History of organ allograft (except for corneal transplant) or autologous or allogeneic bone marrow transplant, or stem cell rescue within 3 months prior to the first dose of acasunlimab * Serious, non-healing wound, skin ulcer (of any grade), or bone fracture * Any history of intracerebral arteriovenous malformation, cerebral aneurysm, new (younger than 6 months) or progressive brain metastases or stroke * Prior therapy: * Radiotherapy within 14 days prior to first dose of acasunlimab. Note: palliative radiotherapy will be allowed. * Treatment with an anti-cancer agent (within 28 days or after at least 5 half-lives of the drug, whichever is shorter), prior to acasunlimab administration. Accepted exceptions are bisphosphonates (e.g., pamidronate, zoledronic acid, etc.) and denosumab * Toxicities from previous anti-cancer therapies that have not adequately resolved NOTE: Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose Escalation: Number of Participants With Dose Limiting Toxicities (DLT) | During first cycle (21 days) | In this trial, a DLT was defined as any grade 5 toxicity, grade 4 neutropenia lasting more than 7 days, grade 3 and 4 febrile neutropenia, grade 4 thrombocytopenia for minimal duration of 7 days, grade 3\&4 hemorrhage associated with thrombocytopenia of ≥ grade 3 requiring platelet transfusion, grade 4 anemia, liver toxicity (transaminases and bilirubin elevations), grade 3 nausea that didn't respond to optimal antiemetic treatment within 7 days, grade ≥3 vomiting that didn't respond to optimal antiemetic treatment within 3 days, grade ≥3 diarrhea that didn't respond to optimal antidiarrheal treatment within 3 days, grade 3 immune-related adverse event (irAEs) that didn't improve to ≤ grade 1 within 7 days by appropriate care or with corticosteroids (with exceptions per protocol), any grade 4 irAE, any other ≥ grade 3 non-hematological adverse events (AE), which occurred during the first GEN1046 treatment cycle (with exceptions per protocol). |
| Dose Escalation and Monotherapy Expansion Cohorts: Number of Participants With Treatment-emergent Adverse Events (AEs) | Up to approximately 5 years, 10 months | An AE was defined as any untoward medical occurrence in a clinical trial participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE was therefore any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. Treatment-emergent AEs were any AEs that developed or worsened after the first dose of a medicinal product. A summary of all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section. |
| Expansion Cohort 1: Objective Response Rate (ORR) | Up to approximately 5 years, 10 months | ORR was defined as the percentage of participants with best overall response (BOR) of complete response (CR) or partial response (PR) based on response evaluation criteria in solid tumors (RECIST v1.1). CR was defined as disappearance of all target lesions. Any pathological lymph nodes must have had a reduction in short axis to \<10 millimeters (mm). PR was defined as ≥30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum of LDs. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Combination Therapy Expansion Cohorts: Number of Participants With Treatment-emergent AEs | Up to approximately 5 years, 10 months | An AE was defined as any untoward medical occurrence in a clinical trial participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE was therefore any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. Treatment-emergent AEs were any AEs that developed or worsened after the first dose of a medicinal product. A summary of all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section. |
| Dose Escalation: Area Under the Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (AUClast) of GEN1046 | Cycle 1 and Cycle 2 (cycles were 21 days) | Venous blood samples were collected for measurement of plasma concentrations of GEN1046. Data reported are average values for Cycle 1 and Cycle 2. |
| Dose Escalation: Maximum Observed Plasma Concentration (Cmax) of GEN1046 | Cycle 1 and Cycle 2 (cycles were 21 days) | Venous blood samples were collected for measurement of plasma concentrations of GEN1046. Data reported are average values for Cycle 1 and Cycle 2. |
| Number of Participants With Anti-drug Antibodies (ADAs) to GEN1046 | Up to approximately 5 years, 10 months | Venous blood samples were collected for measurement of serum concentrations of ADAs. A participant was considered as positive overall status if: (i) negative at baseline and at least one positive post-baseline result; or (ii) positive at baseline and at least one positive post-baseline result with a titer higher than baseline. |
| Dose Escalation and Expansion Cohorts 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13: ORR | Up to approximately 5 years, 10 months | ORR was defined as the percentage of participants with BOR of CR or PR based on RECIST. CR was defined as disappearance of all target lesions. Any pathological lymph nodes must have had a reduction in short axis to \<10 mm. PR was defined as ≥30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum of LDs. |
| Dose Escalation and Expansion Cohorts 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13: Disease Control Rate (DCR) | Up to approximately 5 years, 10 months | DCR was defined as the percentage of participants with confirmed BOR of CR, PR, or stable disease (SD) according to RECIST v1.1. CR was defined as disappearance of all target lesions. Any pathological lymph nodes must have had a reduction in short axis to \<10 mm. PR was defined as ≥30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum of LDs. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum of LDs while in trial. Follow-up measurements must have met the SD criteria at least once and for a minimum time period of 6 weeks (±7 days) after first treatment. |
| Duration of Response (DoR) | Up to approximately 5 years, 10 months | DOR was defined as the time from first documentation of response (CR or PR) to the date of the first documented progression or death whichever occurred earlier based on RECIST v1.1. DOR only applied to participants whose confirmed best overall response was CR or PR (i.e., responders). |
| Expansion Cohort 1: Progression Free Survival (PFS) | Up to approximately 5 years, 10 months | PFS was defined as the time from Day 1 in Cycle 1 (cycles were 21 days) to the first documented progression or death due to any cause, whichever occurred first based on RECIST version 1.1. |
| Expansion Cohort 1: Overall Survival (OS) | Up to approximately 5 years, 10 months | OS was defined as the time from Day 1 in Cycle 1 (cycles were 21 days) to death due to any cause. |
Countries
Czechia, Georgia, Hungary, Israel, Italy, Poland, Spain, Turkey (Türkiye), Ukraine, United States
Contacts
STUDY_DIRECTORStudy Official
Genmab
Participant flow
Pre-assignment details
This trial is ongoing. These primary analysis results only are reported. Final analysis results will be reported after the end of trial.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 3 Participants |
| Age, Categorical Between 18 and 65 years | 249 Participants |
| Age, Continuous | 61.6 years STANDARD_DEVIATION 11 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants |
| Race/Ethnicity, Customized Asian Indian | 0 Participants |
| Race/Ethnicity, Customized Asian Other | 0 Participants |
| Race/Ethnicity, Customized Black or African American | 17 Participants |
| Race/Ethnicity, Customized Chinese | 0 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 0 Participants |
| Race/Ethnicity, Customized Japanese | 0 Participants |
| Race/Ethnicity, Customized Malay | 0 Participants |
| Race/Ethnicity, Customized Missing | 0 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 405 Participants |
| Race/Ethnicity, Customized Not Reported | 0 Participants |
| Race/Ethnicity, Customized Other | 0 Participants |
| Race/Ethnicity, Customized White | 5 Participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 5 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 | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk | EG012 affected / at risk | EG013 affected / at risk | EG014 affected / at risk | EG015 affected / at risk | EG016 affected / at risk | EG017 affected / at risk | EG018 affected / at risk | EG019 affected / at risk | EG020 affected / at risk | EG021 affected / at risk | EG022 affected / at risk | EG023 affected / at risk | EG024 affected / at risk | EG025 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 3 / 4 | 5 / 5 | 7 / 9 | 5 / 6 | 6 / 6 | 9 / 9 | 9 / 9 | 8 / 9 | 2 / 4 | 34 / 40 | 16 / 24 | 29 / 38 | 2 / 2 | 26 / 40 | 7 / 8 | 23 / 32 | 14 / 21 | 16 / 19 | 28 / 40 | 7 / 11 | 11 / 20 | 21 / 27 | 5 / 12 | 6 / 10 | 8 / 16 | 6 / 8 |
| other Total, other adverse events | 4 / 4 | 5 / 5 | 9 / 9 | 5 / 6 | 6 / 6 | 9 / 9 | 8 / 9 | 8 / 9 | 4 / 4 | 39 / 40 | 22 / 24 | 38 / 38 | 2 / 2 | 39 / 40 | 8 / 8 | 31 / 32 | 19 / 21 | 18 / 19 | 38 / 40 | 9 / 11 | 20 / 20 | 27 / 27 | 12 / 12 | 10 / 10 | 15 / 16 | 8 / 8 |
| serious Total, serious adverse events | 2 / 4 | 2 / 5 | 6 / 9 | 3 / 6 | 5 / 6 | 8 / 9 | 2 / 9 | 4 / 9 | 2 / 4 | 23 / 40 | 12 / 24 | 19 / 38 | 0 / 2 | 14 / 40 | 2 / 8 | 12 / 32 | 10 / 21 | 7 / 19 | 19 / 40 | 2 / 11 | 9 / 20 | 10 / 27 | 9 / 12 | 2 / 10 | 7 / 16 | 5 / 8 |
Outcome results
None listed