Select Advanced Solid Tumors
Conditions
Brief summary
Brenetafusp (IMC-F106C) is an immune-mobilizing monoclonal T cell receptor against cancer (ImmTAC ®) designed for the treatment of cancers positive for the tumor-associated antigen PRAME. This is a first-in-human trial designed to evaluate the safety and efficacy of brenetafusp in adult participants who have the appropriate HLA-A2 tissue marker and whose cancer is positive for PRAME.
Detailed description
The IMC-F106C-101 Phase 1/2 study will be evaluated in patients with metastatic/unresectable tumors which include select Advanced Solid Tumors and will be conducted in two phases. 1. Phase 1: To identify the Maximum Tolerated Dose (MTD) and/or Recommended Phase 2 dose (RP2D) of brenetafusp as a single agent and administered in combination with chemotherapies, targeted therapies, and monoclonal antibodies. 2. Phase 2: To assess the efficacy of brenetafusp in selected advanced solid tumors.
Interventions
DRUGBrenetafusp
Brenetafusp IV infusions
DRUGBrenetafusp and pembrolizumab
Brenetafusp and pembrolizumab IV infusions
DRUGBrenetafusp and chemotherapy
Brenetafusp and chemotherapy IV infusions
DRUGBrenetafusp and monoclonal antibodies and chemotherapy
Brenetafusp and a monoclonal antibody therapy and chemotherapy
DRUGBrenetafusp and tebentafusp
Brenetafusp and tebentafusp IV infusions
DRUGBrenetafusp and bevacizumab
Brenetafusp and bevacizumab IV infusions
DRUGBrenetafusp and kinase inhibitors
Brenetafusp and oral kinase inhibitors
Sponsors
Immunocore Ltd
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. ECOG PS 0 or 1 2. HLA-A\*02:01 positive 3. PRAME positive tumor 4. Relapsed from, refractory to, or intolerant of standard therapies; or, in combination with standard therapies 5. If applicable, must agree to use highly effective contraception
Exclusion criteria
1. Symptomatic or untreated central nervous system metastasis 2. Recent bowel obstruction 3. Ongoing ascites or effusion requiring recent drainages 4. Significant immune-mediated adverse event with prior immunotherapy (Participants in checkpoint inhibitor combination treatment) 5. Inadequate washout from prior anticancer therapy 6. Significant ongoing toxicity from prior anticancer treatment 7. Out-of-range laboratory values 8. Clinically significant lung, heart, or autoimmune disease 9. Ongoing requirement for immunosuppressive treatment 10. Prior solid organ or bone marrow transplant 11. Active hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV) infection 12. Significant secondary malignancy 13. Hypersensitivity to study drug or excipients 14. Antibiotics, vaccines or surgery within 2-4 weeks prior to the first dose of study intervention 15. Pregnant or lactating participants 16. Any other contraindication for applicable combination partner based on local prescribing information
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Phase 1: Incidence of dose-limiting toxicity (DLT)s | Up to ~28 days after each dose |
| Phase 1: Incidence of adverse events (AE) and serious adverse events (SAE) | Up to 30 days after the last dose of study therapy |
| Phase 1: Number of participants with dose interruptions, dose reductions, or dose discontinuations | Up to ~12 months |
| Phase 1: Number of participants with abnormal laboratory test results (hematology) | Up to 30 days after the last dose of study therapy |
| Phase 1: Number of participants with abnormal laboratory test results (chemistry) | Up to 30 days after the last dose of study therapy |
| Phase 1: Number of participants with abnormal laboratory test results (coagulation) | Up to 30 days after the last dose of study therapy |
| Phase 1: Number of participants with abnormal urinalysis | Up to 30 days after the last dose of study therapy |
| Phase 1: Number of participants with abnormal vital signs | Up to 30 days after the last dose of study therapy |
| Phase 1: Mean change from baseline in QTcF interval | Up to 30 days after the last dose of study therapy |
| Phase 2: Best overall response (BOR) | Up to ~2 years |
Secondary
| Measure | Time frame |
|---|---|
| Phase I: Best Overall Response (BOR) | Up to ~2 years |
| Progression-free survival (PFS) | Up to ~2 years |
| Duration of response (DOR) | Up to ~2 years |
| Overall survival | Up to ~2 years |
| Area under the plasma concentration-time curve (AUC) of brenetafusp | At designated time points up to ~3 weeks |
| Maximum plasma drug concentration (Cmax) of brenetafusp | At designated time points up to ~3 weeks |
| Time to reach maximum plasma concentration (Tmax) of brenetafusp | At designated time points up to ~3 weeks |
| Plasma elimination half-life (t½) of brenetafusp | At designated time points up to ~3 weeks |
| Incidence of anti-brenetafusp antibody formation | Up to ~ 2 years |
| Changes in lymphocyte counts over time | Up to ~3 weeks |
| Changes in serum cytokines over time | Up to ~3 weeks |
| Local tumor response based on Gynecological Cancer Intergroup (GCIG) Cancer Antigen 25 (CA-125) response criteria | Up to ~2 years |
Countries
Australia, Austria, Belgium, Brazil, Canada, France, Germany, Ireland, Italy, Netherlands, New Zealand, Poland, South Korea, Spain, Switzerland, United Kingdom, United States
Outcome results
None listed