A Phase 1 Dose Finding and Phase 2, Randomized, Open-Label Trial to Evaluate the Safety and Clinical Activity of Immunoradiotherapy Combinations as a Treatment Option in Subjects With Metastatic Solid Tumors
Trial Snapshot
- Phase
- Phase 1
- Status
- Terminated
- Sponsor
- Genmab
- Enrollment
- 13
- Locations
- 3
- Primary Endpoint
- Part 1: Number of Participants with Dose Limiting Toxicities (DLTs)
Study Overview
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
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Sequential
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •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.
- •Life expectancy of >3 months.
- •Qualify for palliative radiotherapy as an available option for disease management.
- •Eastern Cooperative Oncology Group (ECOG) 0-
- •Normal or adequate liver, renal, cardiac and bone marrow function.
Exclusion Criteria
- •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.
Arms & Interventions
Radiotherapy + GEN1042
Intervention: GEN1042 (Biological)
Radiotherapy + GEN1042
Intervention: Radiotherapy (Radiation)
Radiotherapy + GEN1042 + Pembrolizumab
Intervention: Pembrolizumab (Drug)
Radiotherapy + GEN1042 + Pembrolizumab
Intervention: GEN1042 (Biological)
Radiotherapy + GEN1042 + Pembrolizumab
Intervention: Radiotherapy (Radiation)
Outcomes
Primary Outcomes
Part 1: Number of Participants with Dose Limiting Toxicities (DLTs)
Time Frame: 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
Time Frame: Up to 12 months after the last radiation treatment
Assessed by investigator.
Number of Participants With Dose Limiting Toxicities (DLTs)
Time Frame: 21 days
A DLT was defined as any grade 5 toxicity, treatment-related toxicity that caused the participant to discontinue treatment during Cycle 1, febrile neutropenia grade 3 or grade 4, grade 3 thrombocytopenia associated with clinically significant bleeding, grade 4 thrombocytopenia of any duration, grade 4 anemia, any grade ≥3 non-hematologic clinical (non-laboratory) toxicity with exceptions per protocol, any grade 3 or grade 4 non-hematologic laboratory value if clinically significant medical intervention was required to treat the participant or the abnormality led to hospitalization, or the abnormality persisted for \>7 days, and the abnormality resulted in a drug-induced liver injury (DILI) as defined by Hy's Law. Toxicities were graded for severity according to the National Cancer Institute-Common Terminology Criteria for Adverse Events Version 5.0 (NCI-CTCAE v5.0).
Secondary Outcomes
- Parts 1 and 2: Objective Response Rate (ORR)(Up to 2 years)
- Parts 1 and 2: Duration of Response (DOR)(Up to 2 years)
- Parts 1 and 2: Disease Control Rate (DCR)(Up to 2 years)
- Parts 1 and 2: Progression Free Survival (PFS)(Up to 2 years)
- Parts 1 and 2: One- year Overall Survival (OS)(Up to 2 years)
- Part 1: Number of Participants With Abscopal Response in Non-irradiated Target Lesions(Up to 12 months after the last radiation treatment)
- 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: Number of Participants with Anti-drug Antibodies (ADAs)(Predose at multiple timepoints up to 30 days after last dose)
- Objective Response Rate (ORR)(Up to approximately 2 years 5 months)
- Duration of Response (DOR)(Up to approximately 2 years 5 months)
- Disease Control Rate (DCR)(Up to approximately 2 years 5 months)
- Progression Free Survival (PFS)(Up to approximately 2 years 5 months)
- Overall Survival (OS)(Up to approximately 2 years 5 months)
- Number of Participants With Abscopal Response in Non-irradiated Target Lesions As Assessed by the Investigator(Up to approximately 2 years 5 months)
- Number of Participants With Treatment-emergent Adverse Events (TEAEs)(Up to approximately 2 years 5 months)
- Blood Concentration of GEN1042 Over Time(At multiple timepoints (as described in the "Outcome Measure Description" field between Cycle 1 Day 1 up to Safety Follow Up [up to approximately Day 517]). Cycles were 21 days in length.)
- Number of Participants With Anti-drug Antibodies (ADAs)(Up to approximately 2 years 5 months)
- Parts 1 and 2: Plasma Concentration of GEN1042(Predose and postdose at multiple timepoints up to 30 days after last dose)