Safety and Efficacy of IMC-F106C as a Single Agent and in Combination With Checkpoint Inhibitors
- Conditions
- Select Advanced Solid Tumors
- Interventions
- Drug: Brenetafusp and chemotherapyDrug: Brenetafusp and monoclonal antibodies and chemotherapyDrug: Brenetafusp and bevacizumabDrug: Brenetafusp and kinase inhibitors
- Registration Number
- NCT04262466
- Lead Sponsor
- Immunocore Ltd
- 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 patients 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 727
- ECOG PS 0 or 1
- HLA-A*02:01 positive
- PRAME positive tumor
- Relapsed from, refractory to, or intolerant of standard therapies; or, in combination with standard therapies
- If applicable, must agree to use highly effective contraception
- Symptomatic or untreated central nervous system metastasis
- Recent bowel obstruction
- Ongoing ascites or effusion requiring recent drainages
- Significant immune-mediated adverse event with prior immunotherapy (patients in checkpoint inhibitor combination treatment)
- Inadequate washout from prior anticancer therapy
- Significant ongoing toxicity from prior anticancer treatment
- Out-of-range laboratory values
- Clinically significant lung, heart, or autoimmune disease
- Ongoing requirement for immunosuppressive treatment
- Prior solid organ or bone marrow transplant
- Active hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV) infection
- Significant secondary malignancy
- Hypersensitivity to study drug or excipients
- Antibiotics, vaccines or surgery within 2-4 weeks prior to the first dose of study intervention
- Pregnant or lactating
- Any other contraindication for applicable combination partner based on local prescribing information
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Brenetafusp and Anti-PD(L)1 Agent Brenetafusp and pembrolizumab Participants receive brenetafusp and pembrolizumab. Brenetafusp and Chemotherapy Brenetafusp and chemotherapy Participants receive brenetafusp and chemotherapy. Choice of chemotherapy is dependent on cohort. Brenetafusp and Targeted Therapy Brenetafusp and tebentafusp Participants receive brenetafusp and a selected targeted therapy. Receipt of kinase inhibitor is dependent on histology. Brenetafusp and Targeted Therapy Brenetafusp and bevacizumab Participants receive brenetafusp and a selected targeted therapy. Receipt of kinase inhibitor is dependent on histology. Brenetafusp and Targeted Therapy Brenetafusp and kinase inhibitors Participants receive brenetafusp and a selected targeted therapy. Receipt of kinase inhibitor is dependent on histology. Brenetafusp and Multimodal Therapy Brenetafusp and monoclonal antibodies and chemotherapy Participants receive brenetafusp, biologics (eg, pembrolizumab, bevacizumab) IV infusions and chemotherapy IV infusions based on histology. Brenetafusp Monotherapy Brenetafusp Participants receive brenetafusp.
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method 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
Trial Locations
- Locations (76)
University of California - San Diego
🇺🇸La Jolla, California, United States
Angeles Clinic and Research Institute
🇺🇸Los Angeles, California, United States
University of California Davis Comprehensive Center
🇺🇸Sacramento, California, United States
University of Colorado
🇺🇸Aurora, Colorado, United States
Georgetown University Medical Center
🇺🇸Washington, District of Columbia, United States
Houston Lee Moffitt Cancer Center & Research Institute
🇺🇸Tampa, Florida, United States
The University of Chicago Medical Center
🇺🇸Chicago, Illinois, United States
University of Iowa
🇺🇸Iowa City, Iowa, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
John Theurer Cancer Center at Hackensack University Medical Center
🇺🇸Hackensack, New Jersey, United States
Scroll for more (66 remaining)University of California - San Diego🇺🇸La Jolla, California, United States