A Study to Assess the Safety and Tolerability of CFT8634 in Locally Advanced or Metastatic SMARCB1-Perturbed Cancers, Including Synovial Sarcoma and SMARCB1-Null Tumors

NCT05355753 | Terminated Phase 1 FDA Drug

• 1 other identifier: CFT8634-1101
• Study Type: interventional
• Target: 49
• Locations: 1 country
• Sites: 12

Brief Summary

This is an open-label, non-randomized, first-in-human Phase 1/2 study designed to evaluate the safety and tolerability of CFT8634 in subjects with synovial sarcoma and SMARCB1-null tumors who: have received prior systemic therapy; have relapsed/refractory tumors; have unresectable or metastatic disease; and are not candidates for available therapies known to confer clinical benefit. The study will characterize the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of CFT8634.

Conditions

Synovial Sarcoma; Soft Tissue Sarcoma

Keywords

Synovial Sarcoma; SMARB1-Null Tumors; CFT8634; Soft Tissue Sarcoma; Myoepithelial Carcinoma; Extraskeletal Myxoid Chondrosarcoma; Renal Medullary Carcinoma; Chordoma; Epithelioid Sarcoma

Outcome Measures

Primary Outcomes (5)

• Frequency and severity of AEs and serious adverse events (SAEs)

  Phase 1 and Phase 2

  From screening until at least 30 days after completion of study treatment

• Number of subjects with changes between baseline and post-baseline safety assessments based on safety laboratory results graded by CTCAE v5.0

  Phase 1 and Phase 2

  From screening until at least 30 days after completion of study treatment

• Frequency of dose interruptions and dose reductions

  Phase 1 and Phase 2

  From first dose until end of treatment

• Incidence of dose limiting toxicities (DLTs)

  Phase 1 only

  From first dose until 28 days after first dose

• Overall Response Rate (ORR)

  Phase 2 only according to RECIST v1.1 criteria

  Up to approximately 24 months

Secondary Outcomes (8)

• Plasma concentration of CFT8634 to characterize the pharmacokinetics (PK) parameters of CFT8634

  At multiple time points up to approximately 24 weeks

• Asses dose proportionality assessment

  At multiple time points up to approximately 24 weeks

• Assess the pharmacodynamics by percent reduction from baseline of target protein

  At multiple time points up to approximately 24 weeks

• ORR

  Up to approximately 24 months

• Duration of Response (DOR)

  Up to approximately 24 months

Study Arms (4)

Dose Escalation Phase 1/Part1: CFT8634

EXPERIMENTAL

Up to approximately 40 subjects ≥18 years of age or between ≥16 and \<18 years of age and weighing ≥50 kg with locally advanced or metastatic SMARCB1-perturbed cancers, including synovial sarcoma and SMARCB1-null tumors, having received ≥ 1 prior anticancer therapy

Drug: CFT8634

Dose Escalation Phase 1/Part 2: CFT8634

EXPERIMENTAL

Up to approximately 6-12 subjects ≥12 and \<16 years of age and weighing ≥40 kg or ≥16 and \<18 years of age and weighing ≥40 kg and \<50 kg with locally advanced or metastatic SMARCB1-perturbed cancers, including synovial sarcoma and SMARCB1-null tumors

Drug: CFT8634

Phase 2 - Arm A: CFT8634

EXPERIMENTAL

Approximately 30 subjects with locally advanced or metastatic synovial sarcoma at the recommended phase 2 dose (RP2D) having received 1-2 prior anticancer therapies

Drug: CFT8634

Phase 2 - Arm B: CFT8634

EXPERIMENTAL

Approximately 20 subjects with locally advanced or metastatic SMARCB1-null tumors at the RP2D having received ≥1 prior anticancer therapy

Drug: CFT8634

Interventions

CFT8634 DRUG

Oral dose of CFT8634

Dose Escalation Phase 1/Part 2: CFT8634; Dose Escalation Phase 1/Part1: CFT8634; Phase 2 - Arm A: CFT8634; Phase 2 - Arm B: CFT8634

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Subject (and legal guardian where applicable) is (are) willing and able to provide signed informed consent (or assent, where applicable) and can follow protocol requirements
• Subject has histologically or cytologically confirmed synovial sarcoma or SMARCB1-null sold tumor that is relapsed/refractory, and unresectable or metastatic; the subject must not be a candidate for available therapies that are known to confer clinical benefit
• a. Phase 1: subject must have received ≥1 prior line of systemic anticancer therapy considered to be Standard of Care per the Investigator's judgment, in the metastatic or unresectable setting b. Phase 2: i. Arm A: subject must have received only 1-2 prior lines of systemic anticancer therapy considered to be Standard of Care per the Investigator's judgment, in the metastatic or unresectable setting ii. Arm B: subject must have received ≥1 prior line of systemic anticancer therapy considered to be Standard of Care per the Investigator's judgment, in the metastatic or unresectable setting
• Subject must be:
• ≥18 years of age (no minimum weight),
• ≥16 and \<18 years old and weighs ≥50 kg,
• ≥12 and \<16 years of age and weighs ≥40kg,
• or ≥16 and \<18 years of age and weighs ≥40kg and \<50kg
• Subject must be able to safely swallow capsules
• Subject must have measurable disease as defined by RECIST v1.1
• Subject must have Eastern Cooperative Oncology Group performance status ≤2 or Lansky performance scale (LK scale) ≥ 60
• Subject must have adequate organ function, defined as:
• Bone marrow function: absolute neutrophil count ≥1.0 x 109/L independent of growth factor support for ≤7 days prior to first dose of study drug for granulocyte colony-stimulating factor and ≤14 days prior to first dose of study drug for peg-filgrastim; hemoglobin ≥8 g/dL independent of transfusion support for ≤7 days prior to first dose of study drug; platelet count ≥75 x 109 /L independent of transfusion support for ≤3 days prior to first dose of study drug
• Coagulation: Prothrombin time (PT)/international normalized ratio (INR) \<1.5x the upper limit of normal (ULN) and activated partial thromboplastin time (aPTT) \<1.5x ULN (unless the subject is receiving anticoagulant therapy and INR and partial PT/aPTT are within therapeutic range of intended use of anticoagulants)
• Liver function: total bilirubin ≤1.5x ULN (≤3.0x ULN for subjects with Gilbert's syndrome), aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3.0x ULN; except for subjects who have tumor infiltration of the liver, where ALT and AST ≤5x ULN

You may not qualify if:

• Subject has had major surgery within 21 days prior to the planned first dose of CFT8634
• a. Minor surgery (eg, minor biopsy of extracranial site, central venous catheter placement, shunt revision) is permitted within 21 days prior to first dose of CFT8634
• Subject has received standard of care or investigational systemic anti-neoplastic therapy within 14 days or 5 half-lives, whichever is shorter, prior to the planned first dose of CFT8634
• Subject has received radiation therapy within 14 days prior to the planned first dose of CFT8634
• Prior treatment with BRD9 degrader
• Subject has central nervous system (CNS) involvement (primary tumor or metastatic disease), except in the following circumstances:
• Subjects with previously treated brain metastases may be permitted to participate provided they are stable (without evidence of progression by imaging 14 days prior to the first dose of study drug and any neurologic symptoms have stabilized), have no evidence of new or enlarging brain metastases, and if they are taking corticosteroids, they are on stable or tapering doses for at least 7 days prior to first dose of study drug. Antiseizure therapy is permitted provided the medication is not otherwise excluded and seizures have been controlled for at least 28 days since the last antiseizure medication adjustment
• Subjects with asymptomatic brain metastases found on Screening magnetic resonance imaging (MRI) may be permitted to be entered into the study without prior radiation therapy to the brain if they do not require immediate surgical or radiation therapy in the opinion of the treating investigator and in the opinion of a radiation therapy or neurosurgical consultant
• Subject has any evidence of a CNS bleed including intra-tumoral hemorrhage
• Subject has known bleeding diathesis
• Subject has impaired cardiac function or clinically significant cardiac disease (i.e. uncontrolled heart disease/hypertension, clinically significant arrythmias, unstable angina/myocardia infarction/stroke within 180 days prior to screening)
• Subject with presence of inflammatory vascular disease or microangiopathy (eg, thrombotic microangiopathies, hemolytic uremic syndrome \[HUS\], atypical HUS)
• Subject with known malignancy, other than study indication, that is progressing or has required treatment within the past 3 years
• a. Subject with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (i.e. breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded
• Subject has received live, attenuated vaccine within 28 days prior to first dose administration

Sponsors & Collaborators

• C4 Therapeutics, Inc.: lead

Study Sites (12)

City of Hope

Duarte, California, 91010, United States

Location

Sarcoma Oncology Research Center

Santa Monica, California, 90403, United States

Location

University of Colorado - Aurora Cancer Center

Aurora, Colorado, 80045, United States

Location

Mayo Clinic - Jacksonville

Jacksonville, Florida, 32224, United States

Location

University of Iowa Hospital and Clinics

Iowa City, Iowa, 52242, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Mayo Clinic - Rochester

Rochester, Minnesota, 55905, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

David H. Koch Center for Cancer Care at Memorial Sloan Kettering Cancer Center

New York, New York, 10021, United States

Location

Columbia University

New York, New York, 10027, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Sarcoma, Synovial; Sarcoma; Chondrosarcoma, Extraskeletal Myxoid; Chordoma

Condition Hierarchy (Ancestors)

Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Germ Cell and Embryonal

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 23, 2022
• First Posted: May 2, 2022
• Study Start: March 25, 2022
• Primary Completion: December 19, 2023
• Study Completion: December 19, 2023
• Last Updated: December 17, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (12)