A Safety and Antitumor Activity Trial of Immunoradiotherapy Combinations as a Treatment Option for Subjects With Metastatic Solid Tumors
Study Details
Study Description
Brief Summary
To evaluate the safety and clinical activity of GEN1042 in combination with radiotherapy with or without pembrolizumab as a treatment option for patients with metastatic solid tumors
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1/Phase 2 |
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
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Radiotherapy + GEN1042
|
Biological: GEN1042
GEN1042 will be administered intravenously (IV)
Other Names:
Radiation: Radiotherapy
Radiotherapy in combination with GEN1042 with or without pembrolizumab
|
| Experimental: Radiotherapy + GEN1042 + pembrolizumab
|
Biological: GEN1042
GEN1042 will be administered intravenously (IV)
Other Names:
Drug: Pembrolizumab
Pembrolizumab will be administered IV in combination with GEN1042
Other Names:
Radiation: Radiotherapy
Radiotherapy in combination with GEN1042 with or without pembrolizumab
|
Outcome Measures
Primary Outcome Measures
- Part 1: Dose limiting toxicities (DLTs) [During the first cycle (21 days) of each patient]
To determine the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D)
- Part 2: Number of participants with abscopal response in non-irradiated target lesions [Throughout the trial until disease progression/death/lost to follow-up/start of new anticancer therapy or withdrawal of consent, whichever occurs first (an expected average of 5 months)]
Assessed by investigator
Secondary Outcome Measures
- Objective response rate (ORR) [Throughout the trial until disease progression/death/lost to follow-up/start of new anticancer therapy or withdrawal of consent, whichever occurs first (an expected average of 5 months)]
Per RECIST v1.1 as assessed by the investigator
- Duration of response (DOR) [From onset date of response until disease progression/death/lost to follow-up/start of new anticancer therapy or withdrawal of consent, whichever occurs first (an expected average of 5 months)]
Per RECIST v1.1 as assessed by the investigator
- Disease control rate (DCR) [Throughout the trial until disease progression/death/lost to follow-up/start of new anticancer therapy or withdrawal of consent, whichever occurs first (an expected average of 5 months)]
Per RECIST v1.1 as assessed by investigator
- Progression-free survival (PFS) [From first dose (part 1) or randomization (part 2) to first documented progression or death due to any cause (an expected average of 5 months)]
Per RECIST v1.1 as assessed by investigator
- Overall survival (OS) [From first dose of GEN1042 (part 1) or randomization (part 2) to date of death (assessed up to 3 years after the last participant's first dose in the trial)]
Defined as the time from first administration of GEN1042 (part 1) or randomization (part 2) to date of death due to any cause
- Part 1: Number of participants with abscopal response in non-irradiated target lesions [Throughout the trial until disease progression/death/lost to follow-up/start of new anticancer therapy or withdrawal of consent, whichever occurs first (an expected average of 5 months)]
Assessed by investigator
- Incidence and severity of adverse events (AEs) [Throughout the trial until end of safety follow-up period (30 days or 90 days after last dose)]
Treatment emergent AEs (TEAEs) All participants should attend a safety follow-up visit 30 days after last dose. Only a proportion of the participants should also attend a safety follow-up visit 90 days after last dose.
- Number of participants with clinically significant shifts from baseline in safety laboratory parameters [Throughout the trial until end of safety follow-up period (30 days or 90 days after last dose)]
Safety laboratory parameters assessed: hematology, biochemistry, and thyroid function All participants should attend a safety follow-up visit 30 days after last dose. Only a proportion of the participants should also attend a safety follow-up visit 90 days after last dose.
- Area under the concentration-time curve (AUC) of GEN1042 [Throughout the trial until the safety follow-up visit (30 days after last dose)]
- Maximum (peak) concentration (Cmax) of GEN1042 after dosing [Throughout the trial until the safety follow-up visit (30 days after last dose)]
- Elimination half-life (T1/2) of GEN1042 [Throughout the trial until the safety follow-up visit (30 days after last dose)]
- Number of participants with incidence of anti-drug antibodies (ADAs) [Throughout the trial until the safety follow-up visit (30 days after last dose)]
Eligibility Criteria
Criteria
Key Inclusion Criteria:
-
Participants with histologically confirmed non-CNS solid tumor that is metastatic and for whom there is no available standard therapy
-
At least 18 years of age
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Signed informed consent prior to any screening procedures
-
Measurable disease according to RECIST v 1.1
-
Life expectancy of >3 months
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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 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
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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/exclusion criteria may apply.
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Genmab
- BioNTech SE
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- GCT1042-02
- 2022-000509-29