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

Select Advanced Solid Tumors Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03973333
• Other study ID #: IMC-C103C-101
• Status: Terminated
• Phase: Phase 1/Phase 2
• Start date: May 17, 2019
• Est. completion date: September 25, 2023

Study information

• Verified date: March 2024
• Source: Immunocore Ltd
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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. 1. To identify the maximum tolerated dose (MTD) and/or expansion dose of IMC-C103C as a single agent administered intravenously (IV) and subcutaneously (SC) once weekly (Q1W) and administered Q1W in combination with once every 3 weeks (Q3W) atezolizumab. 2. To assess the preliminary anti-tumor activity of IMC-C103C in one or more selected indications, as a single agent administered Q1W.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 75
• Est. completion date: September 25, 2023
• Est. primary completion date: September 25, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. HLA-A*02:01 positive

2. MAGE-A4 positive tumor

3. Eastern Cooperative Oncology Group (ECOG) performance status (PS) [ECOG PS] 0 or 1

4. Selected advanced solid tumors

5. Relapsed from, refractory to, or intolerant of standard therapy

6. Measurable disease per RECIST v1.1 (expansion)

7. If applicable, must agree to use highly effective contraception

Exclusion Criteria:

1. Symptomatic or untreated central nervous system metastasis

2. Inadequate washout from prior anticancer therapy

3. Significant ongoing toxicity from prior anticancer treatment

4. Impaired baseline organ function as evaluated by out-of-range laboratory values

5. Clinically significant cardiac disease

6. Active infection requiring systemic antibiotic therapy

7. Known history of human immunodeficiency virus (HIV)

8. Active hepatitis B virus (HBV) or hepatitis C virus (HCV)

9. Ongoing treatment with systemic steroids or other immunosuppressive therapies

10. Significant secondary malignancy

11. Pregnancy or lactation

Related Conditions & MeSH terms

• Select Advanced Solid Tumors

Intervention

Drug:
• IMC-C103C
Weekly IV infusions
• Atezolizumab
IV infusions every 3 weeks
• IMC-C103C
Weekly subcutaneous Injection

Locations

Country	Name	City	State
Spain	Hospital Universitario Vall d'Hebron	Barcelona
Spain	Clinica Universidad Navarra	Madrid
Spain	Hospital Universitario La Paz - PPDS	Madrid
Spain	Clinica Universidad Navarra	Pamplona
United Kingdom	The Clatterbridge Hospital Cancer Center	Bebington
United Kingdom	Beatson West of Scotland Cancer Centre	Glasgow	Scotland
United Kingdom	Sarah Cannon Research Institute	London
United Kingdom	The Christie NHS Foundation Trust	Manchester
United Kingdom	Royal Marsden Hospital	Sutton
United States	University of Colorado Cancer Center	Aurora	Colorado
United States	The University of Chicago Medicine & Biological Sciences	Chicago	Illinois
United States	MD Anderson Cancer Center	Houston	Texas
United States	The Angeles Clinic and Research Institute	Los Angeles	California
United States	Sarah Cannon Research Institute at Tennessee Oncology	Nashville	Tennessee
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Oklahoma University Medical Center	Oklahoma City	Oklahoma
United States	Thomas Jefferson University Hospital	Philadelphia	Pennsylvania
United States	UPMC Cancer Center	Pittsburgh	Pennsylvania
United States	University of California Davis Comprehenvise Cancer Center	Sacramento	California

Sponsors (1)

Lead Sponsor	Collaborator
Immunocore Ltd

Countries where clinical trial is conducted

United States,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Phase 1: Incidence of dose-limiting toxicities (DLT)		From first dose to DLT period (28 days)
Primary	Phase 1: incidence and severity of adverse events (AE)		from first dose to 30 days after the last dose
Primary	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
Primary	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
Primary	Phase 1: changes in electrocardiogram parameters	QT intervals corrected for heart rate using Fridericia's (cube root) correction (QTcF) interval absolute values and changes from baseline will be summarized	from first dose to 30 days after the last dose
Primary	Phase 1: dose interruptions, reductions, and discontinuations		from first dose through last dose (anticipated for up to 12-24 months)
Primary	Phase 2: Best overall response (BOR)		from first dose to approximately 2 years
Secondary	Phase 2: incidence and severity of adverse events (AE)		from first dose to 30 days after the last dose
Secondary	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
Secondary	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
Secondary	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
Secondary	Phase 2: dose interruptions, reductions, and discontinuations		from first dose through last dose (anticipated for up to 12-24 months)
Secondary	Phase 1: Best overall response		from first dose to approximately 2 years
Secondary	Progression-free survival		from first dose to approximately 2 years
Secondary	Duration of response		from first dose to approximately 2 years
Secondary	Overall survival		from first dose to approximately 2 years
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	Immunogenicity the incidence of anti-drug antibody formation		from first dose to 14 days after the last dose
Secondary	Changes in lymphocyte counts over time		from first dose to approx 4 weeks
Secondary	Changes in serum cytokines over time		from first dose to approx.. 4wks
Secondary	GCIG CA-125 response (ovarian carcinoma)		from first dose to approx.. 30 days after the last dose