Clinical trial NCT03973333: Safety and Efficacy of IMC-C103C as Monotherapy and in Combination With Atezolizumab
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
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
PHASE2
Conditions: Select Advanced Solid Tumors
Keywords: ImmTAC, IMC-C103C, MAGE-A4, immunotherapy
Lead sponsor: Immunocore Ltd
Sponsor class: INDUSTRY
First posted: 2019-06-04
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention 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
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Phase 1: Incidence of dose-limiting toxicities (DLT)
timeFrame: From first dose to DLT period (28 days)
measure: Phase 1: incidence and severity of adverse events (AE)
timeFrame: from first dose to 30 days after the last dose
measure: Phase 1: changes in laboratory parameters
timeFrame: from first dose to 30 days after the last dose
measure: Phase 1: changes in vital signs
timeFrame: from first dose to 30 days after the last dose
measure: Phase 1: changes in electrocardiogram parameters
timeFrame: from first dose to 30 days after the last dose
measure: Phase 1: dose interruptions, reductions, and discontinuations
timeFrame: from first dose through last dose (anticipated for up to 12-24 months)
measure: Phase 2: Best overall response (BOR)
timeFrame: from first dose to approximately 2 years
Secondary outcomes:
measure: Phase 2: incidence and severity of adverse events (AE)
timeFrame: from first dose to 30 days after the last dose
measure: Phase 2: changes in laboratory parameters
timeFrame: from first dose to 30 days after the last dose
measure: Phase 2: changes in vital signs
timeFrame: from first dose to 30 days after the last dose
measure: Phase 2: changes in electrocardiogram parameters
timeFrame: from first dose to 30 days after the last dose
measure: Phase 2: dose interruptions, reductions, and discontinuations
timeFrame: from first dose through last dose (anticipated for up to 12-24 months)
measure: Phase 1: Best overall response
timeFrame: from first dose to approximately 2 years
measure: Progression-free survival
timeFrame: from first dose to approximately 2 years
measure: Duration of response
timeFrame: from first dose to approximately 2 years
measure: Overall survival
timeFrame: from first dose to approximately 2 years
measure: Pharmacokinetics Area under the plasma concentration-time curve (AUC)
timeFrame: from first dose to within approx, 2 weeks of last dose/4 weeks (IMC-C103C AUC will be assessed weekly for 4 weeks)
measure: Pharmacokinetics The maximum observed plasma drug concentration after single dose administration (Cmax)
timeFrame: from first dose to within approx, 2 weeks of last dose/4 weeks (IMC-C103C AUC will be assessed weekly for 4 weeks)
measure: Pharmacokinetics The time to reach maximum plasma concentration (Tmax)
timeFrame: from first dose to within approx, 2 weeks of last dose/4 weeks (IMC-C103C AUC will be assessed weekly for 4 weeks)
measure: Pharmacokinetics The elimination half-life (t1/2)
timeFrame: from first dose to within approx, 2 weeks of last dose/4 weeks (IMC-C103C AUC will be assessed weekly for 4 weeks)
measure: Immunogenicity the incidence of anti-drug antibody formation
timeFrame: from first dose to 14 days after the last dose
measure: Changes in lymphocyte counts over time
timeFrame: from first dose to approx 4 weeks
measure: Changes in serum cytokines over time
timeFrame: from first dose to approx.. 4wks
measure: GCIG CA-125 response (ovarian carcinoma)
timeFrame: from first dose to approx.. 30 days after the last dose
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: The Angeles Clinic and Research Institute
state: California
city: Sacramento
country: United States
facility: University of California Davis Comprehenvise Cancer Center
state: California
city: Aurora
country: United States
facility: University of Colorado Cancer Center
state: Colorado
city: Chicago
country: United States
facility: The University of Chicago Medicine & Biological Sciences
state: Illinois
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Oklahoma City
country: United States
facility: Oklahoma University Medical Center
state: Oklahoma
city: Philadelphia
country: United States
facility: Thomas Jefferson University Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Cancer Center
state: Pennsylvania
city: Nashville
country: United States
facility: Sarah Cannon Research Institute at Tennessee Oncology
state: Tennessee
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d'Hebron
city: Madrid
country: Spain
facility: Clinica Universidad Navarra
city: Madrid
country: Spain
facility: Hospital Universitario La Paz - PPDS
city: Pamplona
country: Spain
facility: Clinica Universidad Navarra
city: Glasgow
country: United Kingdom
facility: Beatson West of Scotland Cancer Centre
state: Scotland
city: Bebington
country: United Kingdom
facility: The Clatterbridge Hospital Cancer Center
city: London
country: United Kingdom
facility: Sarah Cannon Research Institute
city: Manchester
country: United Kingdom
facility: The Christie NHS Foundation Trust
city: Sutton
country: United Kingdom
facility: Royal Marsden Hospital
Study officials:
References: