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

• ClinicalTrials.gov Identifier: NCT04262466
• Recruitment Status: Recruiting
• First Posted: February 10, 2020
• Last Update Posted: April 2, 2024
• Sponsor: Immunocore Ltd
• Information provided by (Responsible Party): Immunocore Ltd

Tracking Information

• First Submitted Date: January 30, 2020
• First Posted Date: February 10, 2020
• Last Update Posted Date: April 2, 2024
• Actual Study Start Date: February 25, 2020
• Estimated Primary Completion Date: June 2026 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 28, 2024)

• Phase 1: Incidence of dose-limiting toxicity (DLT)s [ Time Frame: Up to ~28 days after each dose ]
• Phase 1: Incidence of adverse events (AE) and serious adverse events (SAE) [ Time Frame: Up to 30 days after the last dose of study therapy ]
• Phase 1: Number of participants with dose interruptions, dose reductions, or dose discontinuations [ Time Frame: from first dose through last dose (anticipated for up to 12 months) ]
• Phase 1: Number of participants with abnormal laboratory test results (hematology) [ Time Frame: Up to 30 days after the last dose of study therapy ]
• Phase 1: Number of participants with abnormal laboratory test results (chemistry) [ Time Frame: from first dose to 30 days after the last dose ]
• Phase 1: Number of participants with abnormal laboratory test results (coagulation) [ Time Frame: from first dose to 30 days after the last dose ]
• Phase 1: Number of participants with abnormal urinalysis [ Time Frame: from first dose to 30 days after the last dose ]
• Phase 1: Number of participants with abnormal vital signs [ Time Frame: from first dose to 30 days after the last dose ]
• Phase 1: Mean change from baseline in QTcF interval [ Time Frame: Up to 30 days after the last dose of study therapy ]
• Phase 2: Best overall response (BOR) [ Time Frame: from first dose to approximately 2 years ]

Original Primary Outcome Measures (submitted: February 7, 2020)

• Phase 1: Incidence of Dose-limiting toxicity (DLT)s [ Time Frame: From first dose to DLT period (28 days) ]
• Phase 1: incidence and severity of adverse events (AE) and serious adverse events (SAE) [ Time Frame: from first dose to 30 days after the last dose ]
• Phase 1: changes in laboratory parameters [ Time Frame: from first dose to 30 days after the last dose ]
  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 of anemia, activated partial thromboplastin time prolonged, alanine aminotransferase increased, alkaline phosphatase increased, aspartate aminotransferase increased, blood bilirubin increased, creatinine increased, hemoglobin increased, INR increased, lipase increased, lymphocyte count decreased, lymphocyte count increased, neutrophil count decreased, platelet count decreased, serum amylase increased, white blood cell decreased, hypercalcemia, hyperkalemia, hypermagnesemia, hypernatremia, hypoalbuminemia, hypocalcemia, hypoglycemia, hypokalemia, hypomagnesemia, hyponatremia, chronic kidney disease, proteinuria.
• Phase 1: changes in vital signs [ Time Frame: from first dose to 30 days after the last dose ]
  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 of fever, hypothermia, weight gain, weight loss, hypoxia, hypertension
• Phase 1: changes in electrocardiogram parameters [ Time Frame: from first dose to 30 days after the last dose ]
  QTcF interval absolute values and changes from baseline will be summarized
• Phase 1: dose interruptions, reductions, and discontinuations [ Time Frame: from first dose through last dose (anticipated for up to 12 months) ]
  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
• Phase 2: Best overall response (BOR) [ Time Frame: from first dose to approximately 2 years ]

Current Secondary Outcome Measures (submitted: March 28, 2024)

• Phase I: Best Overall Response (BOR) [ Time Frame: from first dose to approximately 2 years ]
• Progression-free survival (PFS) [ Time Frame: from first dose to approximately 2 years ]
• Duration of response (DOR) [ Time Frame: from first dose to approximately 2 years ]
• Overall survival [ Time Frame: from first dose to approximately 2 years ]
• Pharmacokinetics Area under the plasma concentration-time curve (AUC) [ Time Frame: approximately 3 weeks (IMC-F106C AUC will be assessed for ~3 weeks) ]
• Pharmacokinetics The maximum observed plasma drug concentration (Cmax) [ Time Frame: approximately 3 weeks (IMC-F106C Cmax will be assessed for ~3 weeks) ]
• Pharmacokinetics The time to reach maximum plasma concentration (Tmax) [ Time Frame: approximately 3 weeks (IMC-F106C Tmax will be assessed for ~3 weeks) ]
• Pharmacokinetics The elimination half-life (t1/2) [ Time Frame: approximately 3 weeks (IMC-F106C t1/2 will be assessed for ~ 3 weeks) ]
• Incidence of anti-IMC-F106C antibody formation [ Time Frame: approximately 2 years ]
• Changes in lymphocyte counts over time [ Time Frame: approximately 3 weeks ]
• Changes in serum cytokines over time [ Time Frame: approximately 3 weeks ]
• Local tumor response based on Gynecological Cancer Intergroup (GCIG) Cancer Antigen 25 (CA-125) response criteria [ Time Frame: approximately 2 years ]

Original Secondary Outcome Measures (submitted: February 7, 2020)

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

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Safety and Efficacy of IMC-F106C as a Single Agent and in Combination With Checkpoint Inhibitors
• Official Title: Phase 1/2 Study of IMC-F106C in Advance PRAME-Positive Cancers
• Brief Summary: 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

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.

1. 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 chemotherapies, targeted therapies, and monoclonal antibodies.
2. Phase 2: To assess the efficacy of IMC-F106C in selected advanced solid tumors.

• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: Non-Randomized; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Select Advanced Solid Tumors

Intervention

• Drug: IMC-F106C
  IMC-F106C IV infusions
• Drug: IMC-F106C and pembrolizumab
  IMC-F106C and pembrolizumab IV infusions
• Drug: IMC-F106C and chemotherapy
  IMC-F106C and chemotherapy IV infusions
• Drug: IMC-F106C and monoclonal antibodies and chemotherapy
  IMC-F106C and a monoclonal antibody therapy and chemotherapy
• Drug: IMC-F106C and tebentafusp
  IMC-F106C and tebentafusp IV infusions
• Drug: IMC-F106C and bevacizumab
  IMC-F106C and bevacizumab IV infusions
• Drug: IMC-F106C and kinase inhibitors
  IMC-F106C and oral kinase inhibitors

Study Arms

• Experimental: IMC-F106C Monotherapy
  Participants receive IMC-F106C.
  Intervention: Drug: IMC-F106C
• Experimental: IMC-F106C and Anti-PD(L)1 Agent
  Participants receive IMC-F106C and pembrolizumab.
  Intervention: Drug: IMC-F106C and pembrolizumab
• Experimental: IMC-F106C and Chemotherapy
  Participants receive IMC-F106C and chemotherapy. Choice of chemotherapy is dependent on cohort.
  Intervention: Drug: IMC-F106C and chemotherapy
• Experimental: IMC-F106C and Targeted Therapy
  Participants receive IMC-F106C and a selected targeted therapy. Receipt of kinase inhibitor is dependent on histology.
  Interventions:

  • Drug: IMC-F106C and tebentafusp
  • Drug: IMC-F106C and bevacizumab
  • Drug: IMC-F106C and kinase inhibitors
• Experimental: IMC-F106C and Multimodal Therapy
  Participants receive IMC-F106C, biologics (eg, pembrolizumab, bevacizumab) IV infusions and chemotherapy IV infusions based on histology.
  Intervention: Drug: IMC-F106C and monoclonal antibodies and chemotherapy

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: March 28, 2024): 727
• Original Estimated Enrollment (submitted: February 7, 2020): 170
• Estimated Study Completion Date: June 2026
• Estimated Primary Completion Date: June 2026 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. ECOG PS 0 or 1
2. HLA-A*02:01 positive
3. PRAME positive tumor
4. Relapsed from, refractory to, or intolerant of standard therapies; or, in combination with standard therapies
5. If applicable, must agree to use highly effective contraception

Exclusion Criteria:

1. Symptomatic or untreated central nervous system metastasis
2. Recent bowel obstruction
3. Ongoing ascites or effusion requiring recent drainages
4. Significant immune-mediated adverse event with prior immunotherapy (patients in checkpoint inhibitor combination treatment)
5. Inadequate washout from prior anticancer therapy
6. Significant ongoing toxicity from prior anticancer treatment
7. Out-of-range laboratory values
8. Clinically significant lung, heart, or autoimmune disease
9. Ongoing requirement for immunosuppressive treatment
10. Prior solid organ or bone marrow transplant
11. Active hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV) infection
12. Significant secondary malignancy
13. Hypersensitivity to study drug or excipients
14. Antibiotics, vaccines or surgery within 2-4 weeks prior to the first dose of study intervention
15. Pregnant or lactating
16. Any other contraindication for applicable combination partner based on local prescribing information

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Immunocore Medical Information; 844-466-8661; medical.information@immunocore.com

Contact: Immunocore Medical Information EU; +00 800-744-51111; medinfo.eu@immunocore.com

• Listed Location Countries: Australia, Austria, Belgium, Brazil, Canada, France, Germany, Italy, Korea, Republic of, Netherlands, New Zealand, Poland, Spain, Switzerland, United Kingdom, United States

Administrative Information

• NCT Number: NCT04262466
• Other Study ID Numbers: IMC-F106C-101
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Immunocore Ltd
• Original Responsible Party: Same as current
• Current Study Sponsor: Immunocore Ltd
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Immunocore Ltd
• Verification Date: March 2024