A Safety and Antitumor Activity Trial of Immunoradiotherapy Combinations as a Treatment Option for Subjects With Metastatic Solid Tumors
- Conditions
- Non-CNS Tumor
- Interventions
- Registration Number
- NCT05491317
- Lead Sponsor
- Genmab
- Brief Summary
The main purpose is to assess the safety and clinical activity of GEN1042 in combination with radiotherapy or GEN1042 in combination with radiotherapy and pembrolizumab as a treatment option for participants with metastatic solid tumors.
- Detailed Description
The study will be conducted in two parts: Part 1 (dose-finding) and Part 2 (randomization).
Part 1 will evaluate the safety of immunoradiotherapy combinations and establish the dose(s) to be evaluated in Part 2.
Part 2 will evaluate the anti-tumor activity of immunoradiotherapy combinations at the established dose(s) from Part 1.
Participants in both parts are treated with one of the following combinations:
* Radiotherapy + GEN1042
* Radiotherapy + GEN1042 + Pembrolizumab
While participants in Part 1 are assigned sequentially (GEN1042 without pembrolizumab is investigated first), participants in Part 2 are randomized 1:1 in the two treatment arms.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 88
- Participants with histologically confirmed non-central nervous system (CNS) solid tumor that is metastatic and for whom there is no available standard therapy.
- At least 18 years of age.
- Signed informed consent prior to any screening procedures.
- Measurable disease according to RECIST v1.1.
- Life expectancy of >3 months.
- Qualify for palliative radiotherapy as an available option for disease management.
- Eastern Cooperative Oncology Group (ECOG) 0-1.
- Normal or adequate liver, renal, cardiac and bone marrow function.
Key
- Prior malignancy except for non-melanoma skin cancers and in situ cancers.
- Condition contraindicating radiotherapy.
- Rapidly progressing disease.
- Active, known or suspected autoimmune disease.
- History of non-infectious pneumonitis that required steroids or currently has pneumonitis.
- Contraindications to the use of pembrolizumab.
- Condition requiring systemic treatment with either corticosteroids or other immunosuppressive medications within 14 days of first treatment.
- Received an allogeneic tissue/solid organ transplant.
- Active infection requiring systemic therapy.
Note: Other protocol defined inclusion and exclusion criteria may apply.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Radiotherapy + GEN1042 GEN1042 - Radiotherapy + GEN1042 Radiotherapy - Radiotherapy + GEN1042 + Pembrolizumab GEN1042 - Radiotherapy + GEN1042 + Pembrolizumab Pembrolizumab - Radiotherapy + GEN1042 + Pembrolizumab Radiotherapy -
- Primary Outcome Measures
Name Time Method Part 1: Number of Participants with Dose Limiting Toxicities (DLTs) During the first cycle (Cycle length = 21 days) Toxicities will be graded for severity according to the National Cancer Institute-Common Terminology Criteria for Adverse Events Version 5.0 (NCI-CTCAE v5.0).
Part 2: Number of Participants with Abscopal Response in Non-irradiated Target Lesions Up to 12 months after the last radiation treatment Assessed by investigator.
- Secondary Outcome Measures
Name Time Method Parts 1 and 2: Objective Response Rate (ORR) Up to 2 years ORR is defined as percentage of participants with a confirmed best overall response (BOR) of complete response (CR) or partial response (PR) based on Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST) v1.1 as assessed by investigator.
Parts 1 and 2: Duration of Response (DOR) Up to 2 years DOR is defined as the time from the onset date of response to the date of the first documented progression or death due to any cause based on RECIST v1.1 as assessed by investigator.
Parts 1 and 2: Disease Control Rate (DCR) Up to 2 years The disease control rate (DCR) is defined as the percentage of participants with BOR of CR, PR, and stable disease (SD) according to RECIST v1.1.
Parts 1 and 2: Progression Free Survival (PFS) Up to 2 years PFS is defined as the time from the date of randomization (or date of first administration of GEN1042 ± pembrolizumab treatment for participants in Part 1) to the date of the first documented progression or death due to any cause based on RECIST v1.1 as assessed by investigator.
Parts 1 and 2: One- year Overall Survival (OS) Up to 2 years OS is defined as the time from date of randomization (or date of first administration of GEN1042 ± pembrolizumab treatment for participants in Part 1) to date of death due to any cause.
Part 1: Number of Participants With Abscopal Response in Non-irradiated Target Lesions Up to 12 months after the last radiation treatment Assessed by investigator.
Parts 1 and 2: Number of Participants with Adverse Events (AEs) From screening until the end of the safety follow-up period (30 days or 90 days after last dose) Parts 1 and 2: Area Under the Concentration-time Curve (AUC) of GEN1042 Predose and postdose at multiple timepoints up to 30 days after last dose Parts 1 and 2: Maximum (Peak) Plasma Concentration (Cmax) Predose and postdose at multiple timepoints up to 30 days after last dose Parts 1 and 2: Elimination Half-life (T1/2) of GEN1042 Predose and postdose at multiple timepoints up to 30 days after last dose Parts 1 and 2: Number of Participants with Anti-drug Antibodies (ADAs) Predose at multiple timepoints up to 30 days after last dose
Trial Locations
- Locations (3)
Institut Bergonie
🇫🇷Bordeaux, France
Centre Leon Berard
🇫🇷Lyon, France
Institut Gustave Roussy
🇫🇷Villejuif, France