GEN1042 Safety Trial and Anti-tumor Activity in Participants With Malignant Solid Tumors
- Conditions
- Malignant Solid TumorNon-Small Cell Lung Cancer (NSCLC)Colorectal Cancer (CRC)MelanomaHead and Neck Squamous Cell Carcinoma (HNSCC)Pancreatic Ductal Adenocarcinoma (PDAC)
- Interventions
- Registration Number
- NCT04083599
- Lead Sponsor
- Genmab
- Brief Summary
The goal of this trial is to learn about the antibody GEN1042 when it is used alone and when it is used together with another antibody cancer drug, pembrolizumab (with or without chemotherapy), for treatment of participants with certain types of cancer.
- Detailed Description
This is an open-label, multicenter phase 1/2 study designed to assess the safety, pharmacokinetics, pharmacodynamics and anti-tumor activity of GEN1042 administered as a monotherapy or in combination in participants with metastatic or locally advanced solid tumors.
Participants will receive either GEN1042 alone, GEN1042 with pembrolizumab, or GEN1042 with pembrolizumab and chemotherapy. All participants 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 GEN1042 is safe and to find out the best doses of GEN1042 to use. The purpose of the second part is to give GEN1042 to more participants to see how well the dose(s) of GEN1042 selected in the first part work against cancer with GEN1042 when given alone or in combination with pembrolizumab or in combination with pembrolizumab and chemotherapy.
Trial details include:
* The average trial duration will be about 3 years.
* The treatment duration will be up to 2 years (when GEN1042 is combined with pembrolizumab).
* The visit frequency will be weekly at first and lessening over time until visits are only once every 3 weeks.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 1287
Monotherapy - Dose Escalation and Dose Expansion Parts
- Participants with non-CNS solid tumors that is metastatic or unresectable and for whom there is no available standard therapy.
- Participants with a confirmed diagnosis of relapsed or refractory, advanced and/or metastatic melanoma, NSCLC, or CRC and for whom there is no available standard therapy
Combination Therapy - Dose Expansion Part
- Participants with unresectable Stage III or Stage IV melanoma with no prior systemic anticancer therapy for unresectable or metastatic disease. Primary ocular or mucosal melanoma is excluded.
- Participants with Stage IV metastatic or recurrent NSCLC with no prior systemic anticancer therapy, no actionable mutation.
- Participants with recurrent or metastatic HNSCC with no prior systemic therapy administered in the recurrent or metastatic setting.
- Participants with confirmed metastatic PDAC with no previous radiotherapy, surgery, chemotherapy, or investigational therapy for the treatment of metastatic disease.
General (all phases):
- Must be age ≥ 18 years of age on the day of signing informed consent, or the legal age of consent in the jurisdiction in which the trial is taking place.
- Measurable disease according to RECIST 1.1
- Eastern Cooperative Oncology Group (ECOG) 0-1
- Normal or adequate liver, renal, cardiac and bone marrow function
Key
Monotherapy - Dose Escalation and Dose Expansion Parts
- Treatment with an anti-cancer agent (within 21 days or after at least 5 half-lives of the drug, whichever is shorter), prior to GEN1042 administration
- Radiotherapy within 14 days prior to first GEN1042 administration
- Toxicities from previous anti-cancer therapies that have not resolved
Combination Therapy - Dose Expansion Part
- Has received prior systemic cytotoxic chemotherapy, biological therapy, OR major surgery within 3 weeks or at least 5 half-lives of the drug (whichever is shorter) of the first dose of trial treatment.
- Radiotherapy within 14 days of start of trial treatment or received lung radiation therapy of > 30 Gy within 6 months of the first dose of trial treatment.
General (all phases)
- Participants has an active, known, or suspected autoimmune disease.
- History of non-infectious pneumonitis that required steroids or currently has pneumonitis.
- History of ≥ grade 3 allergic reactions to monoclonal antibody (mAb) therapy
- Participants with a condition requiring systemic treatment with either corticosteroids (>10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of first treatment.
NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Monotherapy - Dose Escalation and Dose Expansion Parts GEN1042 - Combination Therapy - Safety Run-in and Expansion Parts GEN1042 - Combination Therapy - Safety Run-in and Expansion Parts Pembrolizumab - Combination Therapy - Safety Run-in and Expansion Parts Cisplatin - Combination Therapy - Safety Run-in and Expansion Parts Carboplatin - Combination Therapy - Safety Run-in and Expansion Parts 5-FU - Combination Therapy - Safety Run-in and Expansion Parts Gemcitabine - Combination Therapy - Safety Run-in and Expansion Parts Nab paclitaxel - Combination Therapy - Safety Run-in and Expansion Parts Pemetrexed - Combination Therapy - Safety Run-in and Expansion Parts Paclitaxel -
- Primary Outcome Measures
Name Time Method Dose Escalation and Safety Run-in Parts: Number of Participants With Dose-Limiting Toxicities (DLTs) First Cycle (21 days) Toxicities will be graded for severity according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) criteria version 5.0
Dose Expansion: Objective Response Rate (ORR) Up to approximately 3 years ORR is defined as the percentage of participants with best overall response (BOR) \[complete or partial response (PR or CR)\] based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 as assessed by the investigator.
- Secondary Outcome Measures
Name Time Method All Parts: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) From first dose until the end of the study (approximately 3 years) Dose Escalation: ORR Up to approximately 3 years ORR is defined as the percentage of participants with BOR (PR or CR) based on RECIST version 1.1 as assessed by the investigator.
All Parts: Duration of Objective Response (DOR) Up to approximately 3 years DOR is defined as time from the first documentation of objective tumor response (CR or PR) to the date of first progressive disease (PD) or death based on RECIST version 1.1 as assessed by the investigator.
All Parts: Disease Control Rate (DCR) Up to approximately 3 years DCR is defined as the percentage of participants with BOR of CR, PR, or stable disease (SD) based on RECIST version 1.1 as assessed by the investigator.
All Parts: Progression-Free Survival (PFS) Up to approximately 3 years PFS is defined as the time from Day 1 in Cycle 1 to the first documented progression or death due to any cause based on RECIST version 1.1 as assessed by the investigator.
All Parts: Overall Survival (OS) Up to approximately 3 years OS is defined as time from Day 1 in Cycle 1 to death due to any cause.
All Parts: Area Under the Concentration-Time Curve (AUC) of GEN1042 Predose and postdose at multiple timepoints up to end of treatment (approximately 2 years) All Parts: Maximum Observed Plasma Concentration (Cmax) of GEN1042 Predose and postdose at multiple timepoints up to end of treatment (approximately 2 years) All Parts: Half-life (t½) of GEN1042 Predose and postdose at multiple timepoints up to end of treatment (approximately 2 years) All Parts: Number of Participants With Anti-drug Antibody (ADA) Response to GEN1042 Predose and postdose at multiple timepoints up to end of treatment (approximately 2 years) Serum samples will be screened for antibodies binding to GEN1042 and the titer of confirmed positive samples will be reported.
Trial Locations
- Locations (75)
Alaska Oncology and Hematology LLC
🇺🇸Anchorage, Alaska, United States
Cancer & Blood Specialty Clinic
🇺🇸Los Alamitos, California, United States
Moores Cancer Center at the UC San Diego Health
🇺🇸San Diego, California, United States
Yale University Cancer Center
🇺🇸New Haven, Connecticut, United States
ChristianaCare
🇺🇸Newark, Delaware, United States
Mount Sinai Comprehensive Cancer Center
🇺🇸Miami Beach, Florida, United States
Florida Cancer Affiliates
🇺🇸Ocala, Florida, United States
Hope and Healing Cancer Services
🇺🇸Hinsdale, Illinois, United States
University of Kentucky
🇺🇸Lexington, Kentucky, United States
Norton Cancer Institute
🇺🇸Louisville, Kentucky, United States
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