A Study of FT-2102 in Patients with Advanced Solid Tumors and Gliomas

Phase 1

• Conditions: Advanced Solid Tumors and Gliomas with an IDH1 Mutation; MedDRA version: 20.0Level: PTClassification code 10018338Term: GliomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 21.1Level: PTClassification code 10008734Term: ChondrosarcomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 21.1Level: PTClassification code 10073073Term: Hepatobiliary cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 21.1Level: LLTClassification code 10065252Term: Solid tumorSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.0Level: LLTClassification code 10073077Term: Intrahepatic cholangiocarcinomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2018-001796-21-GB
• Lead Sponsor: Forma Therapeutics, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2018-10-01
• Last Update Posted: 19 October 2020

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 200

Inclusion Criteria

All patients must meet the following criteria for inclusion:
1.=18 years of age
2.Life expectancy of =4 months
3.Able to provide tumor tissue sample (archival)
4.Disease, defined as:
Disease-specific Cohorts
•Glioma (Cohort 1)
Histologically or cytologically confirmed IDH1 gene-mutated advanced glioma that has recurred or progressed following standard therapy, or that has not responded to standard therapy with measurable disease.
Glioblastoma multiforme with confirmed IDH1 gene-mutated disease with first or second recurrence with measurable disease.
HBC (Cohort 2)
Relapsed/refractory or intolerant to approved standard-of-care therapy (included: hepatocellular carcinoma, bile duct carcinoma, intrahepatic cholangiocarcinoma or other hepatobiliary carcinomas)
Histologically or cytologically confirmed IDH1 gene-mutated with measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria.
Child-Pugh Class A
Single Agent FT-2102: prior exposure to nivolumab is permitted
Combination Cohort 2b: patients may not have had prior exposure to nivolumab.

•Chondrosarcoma (Cohort 3)
Relapsed or refractory and either locally advanced or metastatic and not amenable tocomplete surgical excision
Histologically or cytologically confirmed IDH1 gene-mutated with measurabledisease per RECIST 1.1 criteria.
•IHCC (Cohort 4)
Advanced nonresectable or metastatic intrahepatic cholangiocarcinoma not eligiblefor curative resection or transplantation.
Single-Agent/Safety Lead-in of Combination Phase 2: ineligible for standardtherapies only
Combination Phase 2 (beyond Safety Lead-in): have received no more than 1 cycleof GemCis therapy
Histologically or cytologically confirmed IDH1 gene-mutated with measurabledisease per RECIST 1.1 criteria
•Other tumors (non-CNS) (Cohort 5)
Relapsed or refractory to standard-of-care therapy with no other available therapeuticoptions
Histologically or cytologically confirmed IDH1 gene-mutated with measurabledisease per disease appropriate response criteria.
5.Recovered to =Grade 2 or baseline toxicity (except alopecia) from prior therapy (per CTCAEv 4.03)
6.Eastern Cooperative Oncology Group (ECOG) performance status 0-2
7.Adequate bone marrow function
•Absolute neutrophil count (ANC) =1.5 x 109/L without any growth factors in prior7 days
•Hemoglobin =8.0 g/dL (with or without transfusion support)
Platelet count =75 × 109/L (with or without transfusion support); Cohort 4b (GemCiscombination): platelet count =100 × 109/L (with or without transfusion support)
8.Adequate hepatic function
•Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase)/alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase) =2.5 ×institutional upper limit of normal (ULN). For patients with suspected malignancyrelated elevations, <5 × ULN. Patients with Gilbert Syndrome <3 times ULN.
• Total bilirubin =1.5 × ULN. For patients with suspected malignancy related elevation <3 × institutional ULN.
9. Adequate renal function
• Creatinine clearance per Cockcroft-Gault equation of =60 mL/min
10. For women of childbearing potential (WCBP): negative serum ß human chorionic gonadotropin (ß-hCG) pregnancy test within 1 week before first treatment (WCBP defined as a sexually mature woman who has not undergone surgical sterilization or who has not been naturally post-menopausal for at least 12 consecutive months for women >55 years of age)
11. Willingness of male and female patients who are not surgically sterile or p

Exclusion Criteria

Patients are to be excluded from the study if they meet any of the following criteria:
1. Previous solid organ or hematopoietic cell transplant
2. Less than the minimum time has elapsed from prior anticancer treatment to first dose of study treatment as follows:
• Small molecule, antibody, or other anticancer therapeutic: 21 days (or 5 half-lives), whichever is shorter. Nitrosoureas or mitomycin C: 6 weeks. For patients enrolling in the Phase 2 (beyond Safety Lead-in with IHCC): 14 days from GemCis therapy.
• Prior radiation therapy (including radiofrequency ablation): 4 weeks
• Prior stereotactic body radiation therapy: 2 weeks
• Prior chemoembolization or radioembolization: 4 weeks
3. No previous treatment with an IDH1 inhibitor (single agent FT-2102 cohorts only)
4. Congestive heart failure (New York Heart Association Class III or IV) or unstable angina pectoris; previous history of myocardial infarction within one year prior to study entry, uncontrolled hypertension, or uncontrolled arrhythmias
5. History of QT prolongation or baseline QT interval corrected with Fridericia’s method (QTcF) >450 ms (average of triplicate readings)
NOTE: criterion does not apply to patients with a right or left bundle branch block, a cardiology consult is recommended to assure that QTcF is not prolonged.
6. Concomitant medication(s) associated with QTc interval prolongation or Torsades de Pointes (TdP) initiated less than the duration required to reach steady-state plasma concentration (approximately five half-lives) before first dose of study drug (see Appendix 3) (medications used as needed [PRN] (e.g., Zofran) are exempt).
7. Pregnant or nursing women or WCBP not using adequate contraception; male patients not using adequate contraception
8. Other malignancy within the last 5 years except: adequately treated non-melanoma skin cancer, curatively treated in situ cancer of the cervix, ductal carcinoma in situ, stage 1, grade 1 endometrial carcinoma, or other solid tumors including lymphomas (without bone marrow involvement) curatively treated with no evidence of disease for =5 years
9. Major surgery within 4 weeks of starting study treatment or not recovered from any effects of prior major surgery (uncomplicated central line placement or fine needle aspirate are not considered major surgery)
10. Receipt of a live vaccine (including yellow fever vaccine) within 30 days of first day of study treatment
11. Patients receiving >6 mg/day of dexamethasone or equivalent
12. Patients with gastrointestinal disorders likely to interfere with absorption of the study medication
13. Known human immunodeficiency virus positivity (HIV)
14. Active infection with hepatitis B or C virus (Hep B or C viral load>100 international units/milliliter or local institutional equivalent)
15. Unstable or severe uncontrolled medical condition (e.g., unstable cardiac function, unstable pulmonary condition including pneumonitis and/or interstitial lung disease, uncontrolled diabetes) or any important medical or psychiatric illness or abnormal laboratory finding that would, in the Investigator’s judgment, increase the risk to the patient associated with his or her participation in the study. This includes any condition that would be considered a contraindication per local prescribing information to receipt of either azacitidine, nivolumab, gemcitabine or cisplatin based on cohort assigned (combination patients only).
16. PD-1 combination only:
a. Patients with active autoimmu

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified