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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

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ClinicalTrials.gov Identifier: NCT05355753
Recruitment Status : Recruiting
First Posted : May 2, 2022
Last Update Posted : September 27, 2022
Sponsor:
Information provided by (Responsible Party):
C4 Therapeutics, Inc.

Brief Summary:
The purpose of this study is to characterize the safety, tolerability, pharmacokinetics, pharmacodynamics, and antitumor activity of CFT8634 in subjects with locally advanced or metastatic SMARCB1-perturbed cancers, including synovial sarcoma and SMARCB1-null tumors with unresectable or metastatic disease, following at least 1 prior line of standard-of-care systemic therapy and must not be candidates for therapies available that are known to confer clinical benefit.

Condition or disease Intervention/treatment Phase
Synovial Sarcoma Soft Tissue Sarcoma Drug: CFT8634 Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 110 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1/2 Open-Label, Multicenter Study to Characterize the Safety and Tolerability of CFT8634 in Subjects With Locally Advanced or Metastatic SMARCB1-Perturbed Cancers, Including Synovial Sarcoma and SMARCB1-Null Tumors
Actual Study Start Date : March 25, 2022
Estimated Primary Completion Date : October 2024
Estimated Study Completion Date : May 2025

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Phase 1: CFT8634
Up to approximately 40 subjects ≥18 years of age or ≥16 years of age and ≥50 kg with locally advanced or metastatic SMARCB1-perturbed cancers, including synovial sarcoma and SMARCB1-null tumors
Drug: CFT8634
Oral dose of CFT8634

Experimental: Phase 2 - Arm A: CFT8634
Approximately 30 subjects with locally advanced or metastatic synovial sarcoma at the recommended phase 2 dose (RP2D)
Drug: CFT8634
Oral dose of CFT8634

Experimental: Phase 2 - Arm B: CFT8634
Approximately 20 subjects with locally advanced or metastatic SMARCB1-null tumors at the RP2D
Drug: CFT8634
Oral dose of CFT8634




Primary Outcome Measures :
  1. Frequency and severity of AEs and serious adverse events (SAEs) [ Time Frame: From enrollment until at least 30 days after completion of study treatment ]
    Phase 1 and Phase 2

  2. Number of participants with changes between baseline and post-baseline safety assessments based on safety laboratory results graded by CTCAE v5.0 [ Time Frame: From enrollment until at least 30 days after completion of study treatment ]
    Phase 1 and Phase 2

  3. Number of participants with changes from baseline in ECG parameters [ Time Frame: From enrollment until at least 30 days after completion of study treatment ]
    Phase 1 and Phase 2

  4. Frequency of dose interruptions and dose reductions [ Time Frame: From enrollment until at least 30 days after completion of study treatment ]
    Phase 1 and Phase 2

  5. Incidence of dose limiting toxicities (DLTs) [ Time Frame: From enrollment until at least 30 days after completion of study treatment ]
    Phase 1 only

  6. Overall Response Rate (ORR) [ Time Frame: Up to approximately 30 months ]
    Phase 2 only according to RECIST v1.1 criteria


Secondary Outcome Measures :
  1. Plasma concentration of CFT8634 to characterize the pharmacokinetics (PK) parameters of CFT8634 [ Time Frame: At multiple time points up to 6 weeks ]
    Plasma concentration of CFT8634 at the scheduled timepoints

  2. Assess the pharmacodynamics by percent reduction from baseline of target protein [ Time Frame: At multiple time points up to 6 weeks ]
    Tumor BRD9 degradation at scheduled timepoints

  3. ORR [ Time Frame: Up to approximately 30 months ]
    Phase 1 only according to RECIST v1.1 criteria

  4. Duration of Response (DOR) [ Time Frame: Up to approximately 30 months ]
    DOR defined as time from first assessment of PR or CR to follow-on first assessment of progressive disease (PD)

  5. Progression Free Survival (PFS) [ Time Frame: Up to approximately 40 months ]
    Time from first treatment received until PD

  6. Overall Survival (OS) [ Time Frame: Up to approximately 48 months ]
    OS is defined as the time from first dose of study treatment to the date of death, irrespective of the cause of death. (Phase 2 only)

  7. Time to next treatment [ Time Frame: Up to approximately 48 months ]
    Interval from the date of initiation of a treatment to the date of commencement of the next line of therapy



Information from the National Library of Medicine

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Ages Eligible for Study:   16 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Subject (or legal guardian where applicable) is willing and able to provide signed informed consent (or assent when applicable) and can follow protocol requirements
  2. Subject must have histologically- or cytologically-confirmed disease with unresectable or metastatic disease, following at least 1 prior line of standard-of-care systemic therapy (systemic therapy may be administered with or without the use of surgery or radiation) and must not be candidates for therapies available that are known to confer clinical benefit:

    1. Synovial sarcoma,
    2. SMARCB1-null tumor as determined by immunohistochemistry, fluorescent in situ hybridization, or other equivalent tests like gene mutation analysis
  3. Subjects must be ≥18 years of age or ≥16 years old and weighs ≥50 kg
  4. Subject must have measurable disease as defined by RECIST v1.1
  5. Subject must have Eastern Cooperative Oncology Group performance status ≤2

    a. Adolescent enrichment cohort: Lansky performance scale (LK scale): ≥60

  6. Subject must have adequate organ function, defined as:

    1. 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 pegfilgrastim; 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
    2. 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)
    3. 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
    4. Renal function: must have a creatinine clearance ≥60 mL/min (Cockcroft-Gault equation)
    5. Cardiac function: baseline corrected QT interval using Fredericia's formula ≤470 ms (adolescents 12-17 years of age: ≤450 ms) and a left ventricular ejection fraction ≥50% evaluated via echocardiogram
  7. A female subject may be eligible to participate if she is not pregnant or planning a pregnancy, not breastfeeding, and following protocol mediated guidance to avoid pregnancy
  8. A male subject must have either had a prior vasectomy or agree to use a condom during the treatment period and for at least 90 days after the last dose of study treatment

Exclusion Criteria:

  1. Subject has received major surgery within 3 weeks 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 3 weeks prior to enrollment

  2. 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
  3. Subject has received radiation therapy within 14 days prior to the planned first dose of CFT8634
  4. Subjects with central nervous system (CNS) involvement (primary tumor or metastatic disease), except in the following circumstances:

    1. Subjects with previously treated brain metastases may be permitted to participate provided they are stable (without evidence of progression by imaging 4 weeks prior to the first dose of study treatment 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 treatment. Antiseizure therapy is permitted provided the medication is not otherwise excluded and seizures have been controlled for at least 4 weeks since the last antiseizure medication adjustment
    2. 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
  5. Subject has any evidence of a CNS bleed including intratumoral hemorrhage
  6. Subject has known bleeding diathesis
  7. Subject has impaired cardiac function or clinically significant cardiac disease
  8. Subjects with presence of inflammatory vascular disease or microangiopathy (eg, thrombotic microangiopathies, hemolytic uremic syndrome [HUS], atypical HUS)
  9. Subject with known malignancy, other than study indication, that is progressing or has required treatment within the past 3 years

    a. Subjects with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (eg, breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded

  10. Subjects with known history of human immunodeficiency virus (HIV) infection
  11. Subjects with a history of hepatitis B virus (HBV) or hepatitis C virus (HCV) infection or at risk for HBV/HCV infection must have a negative HBV/HCV test to be considered eligible for this study

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05355753


Contacts
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Contact: Chief Medical officer (617) 231-0700 clinicaltrials@C4therapeutics.com

Locations
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United States, California
City of Hope Recruiting
Duarte, California, United States, 91010
United States, Colorado
University of Colorado - Aurora Cancer Center Recruiting
Aurora, Colorado, United States, 80045
United States, Florida
Mayo Clinic - Jacksonville Not yet recruiting
Jacksonville, Florida, United States, 32224
United States, Iowa
University of Iowa Hospital and Clinics Not yet recruiting
Iowa City, Iowa, United States, 52242
United States, Massachusetts
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
United States, Missouri
Washington University School of Medicine Recruiting
Saint Louis, Missouri, United States, 63110
United States, New York
David H. Koch Center for Cancer Care at Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10021
Columbia University Not yet recruiting
New York, New York, United States, 10027
United States, Pennsylvania
University of Pennsylvania Abramson Cancer Center Not yet recruiting
Philadelphia, Pennsylvania, United States, 19104
United States, Texas
MD Anderson Cancer Center Not yet recruiting
Houston, Texas, United States, 77030
Sponsors and Collaborators
C4 Therapeutics, Inc.
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Responsible Party: C4 Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT05355753    
Other Study ID Numbers: CFT8634-1101
First Posted: May 2, 2022    Key Record Dates
Last Update Posted: September 27, 2022
Last Verified: September 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by C4 Therapeutics, Inc.:
Synovial Sarcoma
SMARB1-Null Tumors
CFT8634
Soft Tissue Sarcoma
Additional relevant MeSH terms:
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Sarcoma
Sarcoma, Synovial
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Connective Tissue