Title
A Phase 1/2 First-in-Human Study of the Safety and Efficacy of IMC-F106C as a Single Agent and in Combination with Checkpoint Inhibitors in HLA-A*02:01-Positive Participants with Advanced PRAME-Positive Cancers

Description
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

Objective
Primary (Phase 1):
-To assess the safety and tolerability of IMC-F106C and identify the MTD and/or RP2D of IMC-F106C as monotherapy administered IV and SC and in combination with a checkpoint inhibitor, chemotherapy, or another ImmTAC molecule in advanced solid tumors
-To characterize the initial efficacy of IMC-F106C as monotherapy in selected advanced solid tumors

(Phase 2):
-To characterize the efficacy of IMC-F106C as monotherapy in selected advanced solid tumors

Secondary:
-To assess the antitumor efficacy of IMC-F106C as monotherapy IV and SC and in combination with a
checkpoint inhibitor, chemotherapy, or another ImmTAC molecule
-To characterize the PK profile of IMC-F106C as monotherapy IV and SC and in combination with a
checkpoint inhibitor, chemotherapy, or another ImmTAC molecule
-To evaluate the frequency of antibody formation against IMC-F106C following treatment with IMC-F106C as monotherapy IV and SC and in combination with a checkpoint inhibitor, chemotherapy, or another ImmTAC molecule
-To determine pharmacodynamic changes in peripheral cytokines and lymphocyte counts following treatment with IMC-F106C as monotherapy IV and SC and in combination with a checkpoint inhibitor, chemotherapy, or another ImmTAC molecule

Treatment Experimental: IMC-F106C - Arm A - Phase 1 and Phase 2
Phase 1 dose escalation and Phase 2 monotherapy dose expansion
Drug: IMC-F106C
IMC-F106C weekly IV infusions or SC injections

Experimental: IMC-F106C and an anti-PD(L)1 agent - Arm B - Phase 1
Dose Escalation
Drug: IMC-F106C and atezolizumab and pembrolizumab
IMC-F106C weekly IV infusions and atezolizumab Q3W IV infusion and pembrolizumab Q6W IV infusion

Experimental: IMC-F106C and chemotherapy - Arm C - Phase 1
Dose Escalation
Drug: IMC-F106C and chemotherapy
IMC-F106C weekly IV infusions and chemotherapy Q1-3W IV infusion

Experimental: IMC-F106C and another ImmTAC - Arm D - Phase 1
Dose Escalation
Drug: IMC-F106C and tebentafusp
IMC-F106C weekly IV infusions and tebentafusp weekly IV infusions

Key Eligibility 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

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

Applicable Disease Sites
Bladder; Breast; Genitourinary cancers, other; Lung; Melanoma/Skin cancer; Ovary; Uterus

Participating Institutions
UW Health Eastpark Medical Center; UW Health University Hospital