Safety and Efficacy of IMC-F106C as a Single Agent and in Combination With Checkpoint Inhibitors

Study Overview
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Brief Summary
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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 IMC-F106C in adult patients who have the appropriate HLA-A2 tissue marker and whose cancer is positive for PRAME

Detailed Description
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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. Phase 1: To identify the Maximum Tolerated Dose (MTD) and/or Recommended Phase 2 dose (RP2D) of IMC-F106C as a single agent and administered in combination with a checkpoint Inhibitor, chemotherapy, or another ImmTAC molecule. Phase 2: To assess the efficacy of IMC-F106C as a single agent in selected advanced solid tumors.

Official Title
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Phase 1/2 Study of IMC-F106C in Advance PRAME-Positive Cancers

Conditions
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Select Advanced Solid Tumors

Intervention / Treatment
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* Drug: IMC-F106C
* Drug: IMC-F106C and atezolizumab and pembrolizumab
* Drug: IMC-F106C and chemotherapy
* Drug: IMC-F106C and tebentafusp


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ECOG PS 0 or 1 HLA-A*02:01 positive PRAME positive tumor Relapsed from, refractory to, or intolerant of standard therapy If applicable, must agree to use highly effective contraception Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the Informed Consent (ICF) and protocol Exclusion Criteria: Symptomatic or untreated central nervous system metastasis Recent bowel obstruction Ascites requiring recurrent paracentesis 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) or hepatitis C virus (HCV) infection Known history of human immunodeficiency virus (HIV) 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: IMC-F106C - Arm A - Phase 1 and Phase 2<br>Phase 1 dose escalation and Phase 2 monotherapy dose expansion | Drug: IMC-F106C<br>* IMC-F106C weekly IV infusions or SC injections<br>|
| Experimental: IMC-F106C and an anti-PD(L)1 agent - Arm B - Phase 1<br>Dose Escalation | Drug: IMC-F106C and atezolizumab and pembrolizumab<br>* IMC-F106C weekly IV infusions and atezolizumab Q3W IV infusion and pembrolizumab Q6W IV infusion<br>|
| Experimental: IMC-F106C and chemotherapy - Arm C - Phase 1<br>Dose Escalation | Drug: IMC-F106C and chemotherapy<br>* IMC-F106C weekly IV infusions and chemotherapy Q1-3W IV infusion<br>|
| Experimental: IMC-F106C and another ImmTAC - Arm D - Phase 1<br>Dose Escalation | Drug: IMC-F106C and tebentafusp<br>* IMC-F106C weekly IV infusions and tebentafusp weekly IV infusions<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase 1: Incidence of Dose-limiting toxicity (DLT)s |  | From first dose to DLT period (28 days) | 
| Phase 1: incidence and severity of adverse events (AE) and serious adverse events (SAE) |  | from first dose to 30 days after the last dose | 
| Phase 1: changes in laboratory parameters | Number of participants with, and rate of, Grade 1, Grade 2, Grade 3, and Grade 4 (as applicable per NCI CTCAE v5.0) laboratory abnormalities | from first dose to 30 days after the last dose | 
| Phase 1: changes in vital signs | Number of participants with, and rate of, Grade 1, Grade 2, Grade 3, and Grade 4 (as applicable per NCI CTCAE v5.0) vital sign abnormalities | from first dose to 30 days after the last dose | 
| Phase 1: changes in electrocardiogram parameters | QTcF interval absolute values and changes from baseline will be summarized | from first dose to 30 days after the last dose | 
| Phase 1: dose interruptions, reductions, and discontinuations | Number of participants with, and rate of, dose interruption, dose reduction, permanent discontinuation of study treatment Number of participants with, and rate of, dose interruption, dose reduction, permanent discontinuation of study treatment due to adverse event Number of participants with, and rate of, dose interruption, dose reduction, permanent discontinuation of study treatment due to treatment-related adverse event | from first dose through last dose (anticipated for up to 12 months) | 
| Phase 2: Best overall response (BOR) |  | from first dose to approximately 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase I: Best Overall Response (BOR) |  | from first dose to approximately 2 years | 
| Progression-free survival (PFS) |  | from first dose to approximately 2 years | 
| Duration of response (DOR) |  | from first dose to approximately 2 years | 
| Overall survival |  | from first dose to approximately 2 years | 
| Pharmacokinetics Area under the plasma concentration-time curve (AUC) |  | approximately 3 weeks (IMC-F106C AUC will be assessed for  3 weeks) | 
| Pharmacokinetics The maximum observed plasma drug concentration (Cmax) |  | approximately 3 weeks (IMC-F106C Cmax will be assessed for  3 weeks) | 
| Pharmacokinetics The time to reach maximum plasma concentration (Tmax) |  | approximately 3 weeks (IMC-F106C Tmax will be assessed for  3 weeks) | 
| Pharmacokinetics The elimination half-life (t1/2) |  | approximately 3 weeks (IMC-F106C t1/2 will be assessed for   3 weeks) | 
| Incidence of anti-IMC-F106C antibody formation |  | approximately 2 years | 
| Changes in lymphocyte counts over time |  | approximately 3 weeks | 
| Changes in serum cytokines over time |  | approximately 3 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ImmTAC, Immunotherapy, Bispecific T cell receptor fusion protein, Immune mobilizing monoclonal T cell receptor against cancer, Checkpoint inhibitor, PD1 / PD-1, PD-L1 / PDL1, Melanoma, Lung Cancer, Ovarian Cancer, Endometrial Cancer, Triple Negative Breast Cancer, NSCLC