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

• Sponsor: C4 Therapeutics, Inc. (Industry)
• Overall Status: Recruiting
• CT.gov ID: NCT05355753
• Collaborator: (none)
• Enrollment: 110
• Locations: 10
• Arms: 3
• Anticipated Duration (Months): 37.2
• Patients Per Site: 11
• Patients Per Site Per Month: 0.3

Study Details

Study Description

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

Study Design

• Study Type: Interventional
• Anticipated 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: Mar 25, 2022
• Anticipated Primary Completion Date: Oct 1, 2024
• Anticipated Study Completion Date: May 1, 2025

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Frequency and severity of AEs and serious adverse events (SAEs) [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 [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 [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 [From enrollment until at least 30 days after completion of study treatment]

   Phase 1 and Phase 2

5. Incidence of dose limiting toxicities (DLTs) [From enrollment until at least 30 days after completion of study treatment]

   Phase 1 only

6. Overall Response Rate (ORR) [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 [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 [At multiple time points up to 6 weeks]

   Tumor BRD9 degradation at scheduled timepoints

3. ORR [Up to approximately 30 months]

   Phase 1 only according to RECIST v1.1 criteria

4. Duration of Response (DOR) [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) [Up to approximately 40 months]

   Time from first treatment received until PD

6. Overall Survival (OS) [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 [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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 16 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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:

3. Synovial sarcoma,

4. SMARCB1-null tumor as determined by immunohistochemistry, fluorescent in situ hybridization, or other equivalent tests like gene mutation analysis

5. Subjects must be ≥18 years of age or ≥16 years old and weighs ≥50 kg

6. Subject must have measurable disease as defined by RECIST v1.1

7. Subject must have Eastern Cooperative Oncology Group performance status ≤2

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

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

2. 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

3. 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)

4. 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

5. Renal function: must have a creatinine clearance ≥60 mL/min (Cockcroft-Gault equation)

6. 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

1. Minor surgery (eg, minor biopsy of extracranial site, central venous catheter placement, shunt revision) is permitted within 3 weeks prior to enrollment

1. 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

2. Subject has received radiation therapy within 14 days prior to the planned first dose of CFT8634

3. Subjects with central nervous system (CNS) involvement (primary tumor or metastatic disease), except in the following circumstances:

4. 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

5. 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

6. Subject has any evidence of a CNS bleed including intratumoral hemorrhage

7. Subject has known bleeding diathesis

8. Subject has impaired cardiac function or clinically significant cardiac disease

9. Subjects with presence of inflammatory vascular disease or microangiopathy (eg, thrombotic microangiopathies, hemolytic uremic syndrome [HUS], atypical HUS)

10. Subject with known malignancy, other than study indication, that is progressing or has required treatment within the past 3 years

1. 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

1. Subjects with known history of human immunodeficiency virus (HIV) infection

2. 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	City of Hope	Duarte	California	United States	91010
2	University of Colorado - Aurora Cancer Center	Aurora	Colorado	United States	80045
3	Mayo Clinic - Jacksonville	Jacksonville	Florida	United States	32224
4	University of Iowa Hospital and Clinics	Iowa City	Iowa	United States	52242
5	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
6	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
7	David H. Koch Center for Cancer Care at Memorial Sloan Kettering Cancer Center	New York	New York	United States	10021
8	Columbia University	New York	New York	United States	10027
9	University of Pennsylvania Abramson Cancer Center	Philadelphia	Pennsylvania	United States	19104
10	MD Anderson Cancer Center	Houston	Texas	United States	77030

Sponsors and Collaborators

• C4 Therapeutics, Inc.

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: C4 Therapeutics, Inc.
• ClinicalTrials.gov Identifier: NCT05355753
• Other Study ID Numbers: CFT8634-1101
• First Posted: May 2, 2022
• Last Update Posted: May 2, 2022
• Last Verified: Apr 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• 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: Sarcoma; Sarcoma, Synovial

Study Results

No Results Posted as of May 2, 2022