Safety and Efficacy of IMC-C103C as Monotherapy and in Combination With Atezolizumab

Study Overview
=================
Brief Summary
-----------------
IMC-C103C is an immune mobilizing monoclonal T cell receptor against cancer (ImmTAC ®) designed for the treatment of cancers positive for the tumor-associated antigen MAGE-A4. This is a first-in-human trial designed to evaluate the safety and efficacy of IMC-C103C in adult patients who have the appropriate HLA-A2 tissue marker and whose cancer is positive for MAGE-A4.

Detailed Description
-----------------
The IMC-C103C-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. To identify the MTD and/or expansion dose of IMC-C103C as a single agent administered IV and SC Q1W and administered Q1W in combination with Q3W atezolizumab. To assess the preliminary anti-tumor activity of IMC-C103C in one or more selected indications, as a single agent administered Q1W.

Official Title
-----------------
A Phase 1/2 First-in-human Study of the Safety and Efficacy of IMC-C103C as Single Agent and in Combination With Atezolizumab in HLA-A*0201-positive Patients With Advanced MAGE-A4-positive Cancer

Conditions
-----------------
Select Advanced Solid Tumors

Intervention / Treatment
-----------------
* Drug: IMC-C103C
* Drug: Atezolizumab
* Drug: IMC-C103C


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: HLA-A*02:01 positive MAGE-A4 positive tumor ECOG PS 0 or 1 Selected advanced solid tumors Relapsed from, refractory to, or intolerant of standard therapy Measurable disease per RECIST v1.1 (expansion) If applicable, must agree to use highly effective contraception Exclusion Criteria: Symptomatic or untreated central nervous system metastasis Inadequate washout from prior anticancer therapy Significant ongoing toxicity from prior anticancer treatment Impaired baseline organ function as evaluated by out-of-range laboratory values Clinically significant cardiac disease Active infection requiring systemic antibiotic therapy Known history of human immunodeficiency virus (HIV) Active hepatitis B virus (HBV) or hepatitis C virus (HCV) Ongoing treatment with systemic steroids or other immunosuppressive therapies Significant secondary malignancy Pregnancy or lactation

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: Sequential from arm monotherapy IV dose escalation is opened first; then monotherapy SC dose escalation, monotherapy expansion and combination dose escalation may run
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: IMC-C103C - Monotherapy IV dose escalation<br>n= approximately 50 patients to establish the MTD/expansion dose | Drug: IMC-C103C<br>* Weekly IV infusions<br>|
| Experimental: IMC-C103C and atezolizumab dose escalation<br>n=approximately 12 patients to establish the MTD/expansion dose | Drug: IMC-C103C<br>* Weekly IV infusions<br>Drug: Atezolizumab<br>* IV infusions every 3 weeks<br>* Other names: TECENTRIQ;|
| Experimental: IMC-C103C - expansion<br>Patients will be enrolled n=9-24 per expansion cohort (up to 4 total): metastatic/unresectable tumors of interest patients treated at the expansion dose of IMC-C103C to assess preliminary anti-tumor efficacy | Drug: IMC-C103C<br>* Weekly IV infusions<br>|
| Experimental: IMC-C103C monotherapy SC dose escalation<br>Patients will be enrolled n=9-12 to establish the MTD/expansion dose | Drug: IMC-C103C<br>* Weekly subcutaneous Injection<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase 1: Incidence of dose-limiting toxicities (DLT) |  | From first dose to DLT period (28 days) | 
| Phase 1: incidence and severity of adverse events (AE) |  | from first dose to 30 days after the last dose | 
| Phase 1: changes in laboratory parameters | Abnormalities will be classified according to NCI CTCAE v5.0 | from first dose to 30 days after the last dose | 
| Phase 1: changes in vital signs | Abnormalities will be classified according to NCI CTCAE v5.0 | 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 |  | from first dose through last dose (anticipated for up to 12-24 months) | 
| Phase 2: Best overall response (BOR) |  | from first dose to approximately 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase 2: incidence and severity of adverse events (AE) |  | from first dose to 30 days after the last dose | 
| Phase 2: changes in laboratory parameters | Abnormalities will be classified according to NCI CTCAE v5.0 | from first dose to 30 days after the last dose | 
| Phase 2: changes in vital signs | Abnormalities will be classified according to NCI CTCAE v5.0 | from first dose to 30 days after the last dose | 
| Phase 2: 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 2: dose interruptions, reductions, and discontinuations |  | from first dose through last dose (anticipated for up to 12-24 months) | 
| Phase 1: Best overall response |  | from first dose to approximately 2 years | 
| Progression-free survival |  | from first dose to approximately 2 years | 
| Duration of response |  | 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) |  | from first dose to within approx, 2 weeks of last dose/4 weeks (IMC-C103C AUC will be assessed weekly for 4 weeks) | 
| Pharmacokinetics The maximum observed plasma drug concentration after single dose administration (Cmax) |  | from first dose to within approx, 2 weeks of last dose/4 weeks (IMC-C103C AUC will be assessed weekly for 4 weeks) | 
| Pharmacokinetics The time to reach maximum plasma concentration (Tmax) |  | from first dose to within approx, 2 weeks of last dose/4 weeks (IMC-C103C AUC will be assessed weekly for 4 weeks) | 
| Pharmacokinetics The elimination half-life (t1/2) |  | from first dose to within approx, 2 weeks of last dose/4 weeks (IMC-C103C AUC will be assessed weekly for 4 weeks) | 
| Immunogenicity the incidence of anti-drug antibody formation |  | from first dose to 14 days after the last dose | 
| Changes in lymphocyte counts over time |  | from first dose to approx 4 weeks | 
| Changes in serum cytokines over time |  | from first dose to approx.. 4wks | 
| GCIG CA-125 response (ovarian carcinoma) |  | from first dose to approx.. 30 days after the last dose | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
ImmTAC, IMC-C103C, MAGE-A4, immunotherapy