Phase I/II Study of IMC-F106C in Advance PRAME-Positive Cancers
Study Identifier:
IMC-F106C-101
CT.gov Identifier:
EudraCT Identifier:
EU Trial (CTIS) Number:
Study Contact Information:
Recruitment Complete
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Study Summary
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 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. Phase 2: To assess the efficacy of IMC-F106C in selected advanced solid tumors. Primary (Phase 1): To assess the safety and tolerability of IMC-F106C and identify the MTD and/or RP2D for the D1D, D8D, and CDD of IMC-F106C as: o A monotherapy in advanced solid tumors o In combination with a checkpoint inhibitor in advanced solid tumors Primary (Phase 2): To characterize the initial efficacy of IMC-F106C as a monotherapy in selected advanced solid tumors To evaluate the safety, preliminary anti-tumor activity and pharmacokinetics of IMC-F106C Stable disease (SD) with any tumor reduction confirmed with ≥ 1 subsequent scan was analyzed based on association with overall survival (OS) for tebentafusp Molecular response was defined ≥ 0.5 log [68%] ctDNA reduction by week 9. PRAME was tested by immunohistochemistry (IHC; PRAME+ defined as H-score ≥1). Efficacy is presented by PRAME− and PRAME+ (documented + and unknown) groups.
Medical Condition
The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.
Phase
The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
I/II
Sex
Female & Male
Age
18+ years
Study Drug
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Study Status
Indicates the current recruitment status or the expanded access status
Recruitment Complete
Requirements information
Inclusion criteria
- ECOG PS 0 or 1
- HLA-A 02:01 positive
- PRAME positive tumor
- Relapsed from, refractory to, or intolerant of standard therapies; or, in combination with standard therapies
- If applicable, must agree to use highly effective contraception
- Participant must be > or = 18 years of age, inclusive, at the time of signing the ICF
- Eastern Cooperative Oncology Group (ECOG) status of 0 or 1 at start of treatment
- HLA-A*02:01-positive (testing by central laboratory)
- PRAME-positive tumor, defined as one of the following:
- Documentation of histologically confirmed diagnosis of a tumor type in which PRAME is expressed in >70% of tumors (eg, cutaneous melanoma, serous ovarian carcinoma, or endometrial carcinoma). Note: availability of an adequate tumor biopsy (as defined in the study Laboratory Manual) for retrospective PRAME testing must be confirmed during Screening
- For tumor types where the frequency of PRAME expression is < or = 70% (eg, NSCLC, SCLC, urothelial carcinoma, TNBC), and tumor types where the frequency of PRAME expression is unknown, tumor PRAME expression must be documented based on testing by the study central laboratory
- Participants who are enrolling in biomarker cohorts must have disease that is amenable to biopsy and consent to undergo tumor biopsies during Screening and treatment
- Participants who are enrolling in Phase 1 must have evaluable disease, and participants who are enrolling in Phase 2 must have measurable disease according to RECIST v1.1
- Participants with metastatic or unresectable solid tumors are eligible for Arm A and Arm B. Participants must meet the indication-specific histology/tumor site requirements specified below:
- - R/M melanoma: All primary sites allowed, including cutaneous, mucosal, and uveal
- - R/M ovarian carcinoma: All histologies allowed; Includes fallopian tube and primary peritoneal cancers
- - R/M uterine carcinoma: All histologies allowed
- - R/M NSCLC: All histologies allowed
- - R/M SCLC: All histologies allowed, including high-grade neuroendocrine large cell lung cancer
- - R/M breast cancer: Triple-negative breast cancer
- - R/M urothelial carcinoma: Tumors are allowed from renal pelvis, ureters, urinary bladder, and urethra
- - Other R/M solid tumors: All histologies allowed (pending availability of a validated assay to assess tumor PRAME expression)
- Participants must have relapsed from, are refractory to, or intolerant of all therapies listed in the protocol for their indication and study phase. These therapies must have been given for unresectable/metastatic disease or given in the adjuvant setting if disease progression occurred during or within 6 months of completing adjuvant therapy. There is no maximum limit on the number of prior therapies received. Biomarker testing requirements are shown in Table 13 in the protocol; additional biomarker test results may be requested if available but are not required for eligibility
Exclusion criteria
- Symptomatic or untreated central nervous system metastasis
- Recent bowel obstruction
- Ongoing ascites or effusion requiring recent drainages
- Significant immune-mediated adverse event with prior immunotherapy (Participants 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), hepatitis C virus (HCV), or human immunodeficiency virus (HIV) infection
- 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 participants
- Any other contraindication for applicable combination partner based on local prescribing information
- Presence of untreated or symptomatic central nervous system (CNS) metastases, leptomeningeal disease, or cord compression. NOTE: Participants with treated CNS lesions may enroll provided all the following apply: a. Treated CNS lesions must be radiographically stable for > or = 2 weeks after intervention (surgery and/or radiation); b. Participants must be neurologically stable off systemic corticosteroids for at least 2 weeks prior to enrollment.
- Bowel obstruction within 3 months prior to the planned first dose of study treatment
- Ongoing ascites requiring recurrent paracentesis (ie, at least twice within 28 days prior to the planned first dose of study treatment)
- Presence of NCI CTCAE > or = Grade 2 toxicity due to prior cancer therapy (except Grade 2 alopecia, Grade 2 stable peripheral neuropathy, Grade 2 endocrine disorder [on stable replacement doses and asymptomatic], Grade 2 hypophosphatemia [on appropriate replacement therapy], and Grade 2 ototoxicity)
- Participants enrolling in Arm B with prior immunotherapy exposure must not have experienced immune-mediated AE (imAE) meeting any of the following criteria: a. Grade 4 imAE; b. imAE resulting in the discontinuation of any prior immunotherapy; c. imAE that failed initial immunosuppressive intervention (eg, corticosteroids, infliximab, mycophenolate mofetil); d. imAE that recurred upon rechallenge; e. Pneumonitis that required oral or IV steroids; f. Any neurological, ocular, or renal imAE
- Receipt of anticancer therapy for the disease under study within the following times prior to the first planned dose of study intervention: a. Cellular therapies (eg, T-cell therapies): 90 days; b. Cytotoxic T-lymphocyte associated protein-4 (CTLA4)-targeted immunotherapies (eg, ipilimumab): 28 days; c. All other immunotherapies, including PD-(L)1-targeted immunotherapies (eg, atezolizumab, pembrolizumab): 21 days; d. All other systemic therapies: 14 days; e. Radiotherapy: 14 days (excepting palliative radiotherapy to a limited field, which may be administered within 14 days, eg, for a focally painful tumor mass)
- Participant with an out-of-range Screening laboratory values defined as shown below. NOTE: Hematology evaluations must be performed > or = 7 days from any blood or blood product transfusion and > or = 14 days from any dose of hematologic growth factor: a. Glomerular filtration rate (calculated using the Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] formula, see Section 10.3) < 50 mL/min; b. Urine protein > or = 2+, unless reflex testing confirms urine protein < 1 g/24h; c. Total bilirubin > 1.5 × upper limit of normal (ULN); participants with Gilbert’s syndrome are excluded if total bilirubin > 3.0 × ULN or direct bilirubin > 1.5 × ULN); d. Alanine aminotransferase > 3 × ULN; e. Aspartate aminotransferase > 3 × ULN; f. Absolute neutrophil count < 1.0 × 109/L; g. Absolute lymphocyte count < 0.5 × 109/L; h. Platelet count < 75 × 109/L; i. Hemoglobin < 8 g/dL; j. Morning cortisol < lower limit of normal (unless the participant has asymptomatic adrenal insufficiency and is receiving stable replacement doses)
- History of pneumonitis requiring oral or intravenous (IV) steroids, evidence of active pneumonitis on Screening chest imaging, or ongoing requirement for intermittent or continuous supplemental oxygen
- Clinically significant cardiac disease or impaired cardiac function, including any of the following: a. Congestive heart failure (New York Heart Association Class > or = 3); b. Uncontrolled hypertension (consistent findings [as defined in Section 8.2.3] of systolic blood pressure [BP] > 160 mmHg or diastolic BP > 110 mmHg); c. History of ventricular arrhythmia currently requiring medical treatment; d. Uncontrolled atrial fibrillation; e. Electrocardiogram QT interval corrected for heart rate by Fridericia’s method (QTcF) > 470 msec during Screening obtained on triplicate ECGs or known history of congenital prolonged QT syndrome; f. Acute myocardial infarction or unstable angina pectoris < or = 6 months prior to Screening
- Active autoimmune disease requiring immunosuppressive treatment, including inflammatory bowel disease (ulcerative colitis or Crohn’s disease), within 5 years of Screening
- Systemic treatment with steroids or any other immunosuppressive drug use within 4 weeks of the planned first dose of study intervention, with the following exceptions: a. Treatment for well-controlled and asymptomatic adrenal insufficiency is permitted, but replacement dosing is limited to prednisone < or = 10 mg daily or the equivalent; b. Local steroid therapies (eg, optic, ophthalmic, intra-articular, or inhaled medications) are acceptable; c. Premedication for allergy to contrast reagent; d. Steroids for management of CNS metastases > 2 weeks prior to the planned first dose of study intervention
Clinical Study Information for Healthcare Providers
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Study Locations
Location
Investigator
Status
Condition(s) Treated at Site
Location
START Madrid, Spain (FJD)
Madrid, Spain, 28040
Investigator
Victor Moreno Garcia
Status
Recruitment Complete
Condition(s) Treated at Site
Solid Tumor