Study to Assess the Safety and Tolerability of CFT7455 in Relapsed/Refractory Non-Hodgkin's Lymphoma or Multiple Myeloma

• ClinicalTrials.gov Identifier: NCT04756726
• Recruitment Status: Recruiting
• First Posted: February 16, 2021
• Last Update Posted: April 14, 2023
• Sponsor: C4 Therapeutics, Inc.
• Information provided by (Responsible Party): C4 Therapeutics, Inc.

Study Description

Brief Summary:

The purpose of this study is to characterize the safety, tolerability, pharmacokinetics, pharmacodynamics, and antitumor activity of CFT7455 administered orally in subjects with Relapsed/Refractory (r/r) Non-Hodgkin's Lymphoma (NHL) or Multiple Myeloma (MM) administered according to different dosing schedules as a single agent and in combination with dexamethasone.

Condition or disease	Intervention/treatment	Phase
Multiple Myeloma; Lymphoma, Non-Hodgkin's	Drug: CFT7455; Drug: Dexamethasone Oral	Phase 1; Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 158 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 1/2 Open-Label Multi-Center Study to Characterize the Safety and Tolerability of CFT7455 in Subjects With Relapsed/Refractory Non-Hodgkin's Lymphoma or Multiple Myeloma
• Actual Study Start Date: April 27, 2021
• Estimated Primary Completion Date: September 7, 2024
• Estimated Study Completion Date: December 7, 2024

Arms and Interventions

Arm	Intervention/treatment
Experimental: Phase 1: Arm A - CFT7455; Participants with r/r NHL or r/r MM will be treated with oral CFT7455 as a single agent administered according to different dosing schedules	Drug: CFT7455; oral CFT7455
Experimental: Phase 1: Arm B1 - CFT7455; Participants with r/r MM will be treated with escalating doses of single agent CFT7455 administered according to different dosing schedules until the determination of maximum tolerated dose (MTD)/recommended Phase 2 dose (RP2D)	Drug: CFT7455; oral CFT7455
Experimental: Phase 1: Arm B2 - CFT7455 in combination with dexamethasone; Participants with r/r MM will be treated with oral CFT7455 in combination with a fixed dose of oral dexamethasone in each cohort	Drug: CFT7455; oral CFT7455; Drug: Dexamethasone Oral; oral dexamethasone [ ≤75 years old: 40 mg once per week (QW) on days 1, 8, 15, and 22; >75 Years old: 20 mg QW on days 1, 8, 15, and 22]
Experimental: Phase 1: Arm C - CFT7455; Participants with r/r NHL will be treated with escalating doses of single agent CFT7455 administered according to different dosing schedules in each cohort until determination of MTD/RP2D	Drug: CFT7455; oral CFT7455
Experimental: Phase 2: Arm 1 - CFT7455; Participants with r/r MM will be treated with oral CFT7455	Drug: CFT7455; oral CFT7455
Experimental: Phase 2: Arm 2 - CFT7455 in combination with dexamethasone; Participants with r/r MM treated with oral CFT7455 in combination with oral dexamethasone	Drug: CFT7455; oral CFT7455; Drug: Dexamethasone Oral; oral dexamethasone [ ≤75 years old: 40 mg once per week (QW) on days 1, 8, 15, and 22; >75 Years old: 20 mg QW on days 1, 8, 15, and 22]
Experimental: Phase 2: Arm 3 - CFT7455; Participants with r/r mantle cell lymphoma (MCL) treated with oral CFT7455	Drug: CFT7455; oral CFT7455
Experimental: Phase 2: Arm 4 - CFT7455; Participants with r/r peripheral T-cell lymphoma (PTCL) treated with oral CFT7455	Drug: CFT7455; oral CFT7455

Outcome Measures

Primary Outcome Measures :

1. Phase 1: Safety and tolerability of CFT7455 [ Time Frame: Days 1-28 ]
   Percent of subjects with adverse events (AEs) with CFT7455 as a single agent
2. Phase 1: Safety and tolerability of CFT7455 for CFT7455 in combination with dexamethasone [ Time Frame: Days 1-28 ]
   Percent of subjects with AEs with CFT7455 in combination with dexamethasone
3. Phase 1: Maximum tolerated dose (MTD) or recommended Phase 2 dose (RP2D) for CFT7455 [ Time Frame: Baseline through 3 months after the last dose of study treatment ]
   Percent of subjects with dose-limiting toxicities (DLTs) with CFT7455 as a single agent
4. Phase 1: MTD or recommended RP2D for CFT7455 in combination with dexamethasone [ Time Frame: Baseline through 3 months after the last dose of study treatment ]
   Percent of subjects with DLTs with CFT7455 in combination with dexamethasone
5. Phase 2: Antitumor activity of CFT7455 [ Time Frame: Baseline through 6 months after the last dose of study treatment, or until disease progression, whichever occurs first ]
   Overall Response Rate (ORR) based on Best Overall Response (BOR), Duration of Response (DOR), Clinical Benefit Rate (CBR), and Progression Free Survival (PFS) of CFT7455
6. Phase 2: Antitumor activity of CFT7455 in combination with dexamethasone [ Time Frame: Baseline through 6 months after the last dose of study treatment, or until disease progression, whichever occurs first ]
   ORR based on BOR, DOR, CBR, and PFS of CFT7455 as a single agent and in combination with dexamethasone in subjects with MM based on International Myeloma Working Group (IMWG) criteria

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Be willing and able to provide signed informed consent for the trial.
2. Age ≥18 years at the time of signed consent.
3. Have histologically or cytologically-confirmed NHL or MM that is r/r disease and must not be candidates for regimens known to provide clinical benefit to be eligible for the study.

4. MM subject must have a documented diagnosis of MM and measurable disease at enrollment. Measurable disease is defined as:

   • M-protein ≥0.5g/dL by Serum Protein Electrophoresis (sPEP) or
   • ≥200mg/24-hour urine collection by Urine Protein Electrophoresis (uPEP) or
   • Serum Free Light Chain (FLC) levels >100 mg/L involved light chain and an abnormal kappa/lambda (κ/λ) ratio in subjects without measurable serum or urine M-protein or
   • For subjects with immunoglobulin class A (IgA), myeloma whose disease can only be reliably measured by quantitative immunoglobulin measurement, a serum IgA level ≥ 0.50g/dL.

5. Prior treatments for MM subjects must have the following:

   • Received at least 3 prior anti-myeloma regimens including at least 2 consecutive cycles of lenalidomide, pomalidomide, a proteasome inhibitor a glucocorticoid and an anti-CD38 antibody (induction with or without a bone marrow transplant with or without maintenance therapy is considered one regimen).
   • Refractory disease defined as disease that is nonresponsive to therapy (failure to achieve minimal response or development of progressive disease) or disease progression within 60 days from the last dose of their last myeloma therapy.
6. NHL subjects must have documented diagnosis of NHL and measurable disease defined by measurable disease (consistent with Lugano classification) defined as at least one lesion that can be accurately measured in at least two dimensions with PET-CT, documented within 4 weeks of their projected cycle one day one (C1D1) visit. Minimum measurement must be >15 mm in the longest diameter.

7. NHL subjects must have received the following regarding prior therapy:

   • Peripheral T-cell Lymphoma: At least one prior line containing alkylator-based chemotherapy. Note: For subjects with Anaplastic Large Cell Lymphoma (ALCL), the subject must also have received CD30 antibody therapy.
   • Mantle Cell Lymphoma: ≥2 lines of therapy, including CD20 antibody and alkylator chemotherapy, and a Bruton's tyrosine kinase (BTK) inhibitor.
   • Follicular Lymphoma: ≥2 lines of therapy, including CD20 antibody therapy and alkylator chemotherapy.
   • Diffuse Large B-cell Lymphoma: ≥2 lines of therapy, including prior CD20 antibody therapy, and has received prior autologous bone marrow transplant (or is ineligible for bone marrow transplant).
   • Other NHL: Subjects must have been treated with all standard of care therapies available to the subject which, in the assessment of the investigator, may be beneficial to the subject.

8. A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:

   • A woman of non-childbearing potential (i.e., physiologically incapable of becoming pregnant) defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea [in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) > 40 MIU/mL and estradiol < 40 pg/mL (<147 pmol/L) must be obtained].
   • Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the contraception methods specified in the study protocol if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of postmenopausal status prior to study enrollment.
   • Agree to having ongoing pregnancy tests during the study and after discontinuation of the study.
9. A male participant 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. Presence of central nervous system (CNS) disease.
2. Has received prior radiotherapy within 2 weeks of start of study treatment.
3. Have active pneumonitis.

4. Have any of the following:

   • Non-secretory or oligosecretory MM
   • Plasma cell leukemia
   • Systemic light chain amyloidosis
   • Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal gammopathy, and Skin changes (POEMS) Syndrome
   • Lymphoblastic lymphoma
   • Mycosis fungoides
   • Sezary syndrome
   • Primary cutaneous T-cell lymphomas
   • Primary CNS lymphoma
   • B-cell or T-cell prolymphocytic leukemia
5. Subjects with a peripheral neuropathy ≥ Grade 2.
6. Known malignancy other than study indication that is progressing or has required treatment within the past three years.
7. Received live, attenuated vaccine within four weeks of first dose.
8. Known history of human immunodeficiency virus (HIV) infection. No HIV testing is required unless mandated by local health authority.
9. Subjects with positive test for Hepatitis B surface (HBS-Ag) or Hepatitis B core (HBc) antigen.
10. Subjects with positive test for hepatitis C (HCV) infection are excluded regardless of viral load. If hepatitis C antibody test is positive, a confirmatory test should be performed. If the test is negative, subject is eligible for this trial.
11. Concurrent administration of strong CYP3A modulators.
12. Is pregnant, breastfeeding, or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of study treatment.
13. Subjects on proton pump inhibitors (PPIs). The last dose of PPIs must be administered seven days prior to administration of study drug. Antacids are acceptable when administered in a staggered dosing manner with CFT7455.

Contacts and Locations

Contacts

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

Locations

United States, Arizona

Mayo Clinic; Recruiting

Phoenix, Arizona, United States, 85054

Principal Investigator: Saurabh Chhabra, MD

United States, California

University of California-San Francisco; Recruiting

San Francisco, California, United States, 94143

Principal Investigator: Thomas Martin, MD

United States, Colorado

Colorado Blood Cancer Institute (Sarah Cannon Research Institute); Recruiting

Denver, Colorado, United States, 80218

Principal Investigator: Jeffrey Matous, MD

United States, Florida

Mayo Clinic; Recruiting

Jacksonville, Florida, United States, 32224

Principal Investigator: Sikander Ailawadhi, MD

United States, Georgia

Emory University Hospital; Recruiting

Atlanta, Georgia, United States, 30322

Principal Investigator: Sagar Lonial, MD

United States, Massachusetts

Massachusetts General Hospital; Recruiting

Boston, Massachusetts, United States, 02114

Principal Investigator: Andrew Yee, MD

Dana-Farber Cancer Institute; Recruiting

Boston, Massachusetts, United States, 02215

Principal Investigator: Paul Richardson, MD

United States, Minnesota

Mayo Clinic; Recruiting

Rochester, Minnesota, United States, 55905

Principal Investigator: Eli Muchtar, MD

United States, Missouri

Washington University School of St. Louis; Recruiting

Saint Louis, Missouri, United States, 63110

Principal Investigator: Neha Mehta-Shah, MD

United States, New York

Mt Sinai Medical Center; Recruiting

New York, New York, United States, 10029

Principal Investigator: Shambavi Richard, MD

Memorial Sloan Kettering Cancer Center; Recruiting

New York, New York, United States, 10065

Principal Investigator: Steven Horwitz, MD

United States, Tennessee

Tennessee Oncology (Sarah Cannon Research Institute); Recruiting

Nashville, Tennessee, United States, 37203

Principal Investigator: Jesus Berdeja, MD

United States, Wisconsin

Medical College of Wisconsin; Recruiting

Milwaukee, Wisconsin, United States, 53226

Principal Investigator: Binod Dhakal, MD

Sponsors and Collaborators

C4 Therapeutics, Inc.

More Information

• Responsible Party: C4 Therapeutics, Inc.
• ClinicalTrials.gov Identifier: NCT04756726
• Other Study ID Numbers: CFT7455-1101
• First Posted: February 16, 2021
• Last Update Posted: April 14, 2023
• Last Verified: April 2023

Individual Participant Data (IPD) Sharing Statement:

• 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.:

Multiple Myeloma; Lymphoma, Non-Hodgkin's; CFT7455; Relapsed; Refractory

Additional relevant MeSH terms:

Lymphoma; Multiple Myeloma; Neoplasms, Plasma Cell; Lymphoma, Non-Hodgkin; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemorrhagic Disorders; Dexamethasone; Anti-Inflammatory Agents; Antiemetics; Autonomic Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Agents