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

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

The purpose of this study is to characterize the safety, tolerability, pharmacokinetics, pharmacodynamics, and antitumor activity of oral cemsidomide (also known as CFT7455) administered at different dosages in subjects with Relapsed/Refractory (r/r) Non-Hodgkin's Lymphoma (NHL) or Multiple Myeloma (MM). Cemsidomide may be administered as a single agent and, in MM only, in combination with oral dexamethasone.

Study Overview

• Status: Active, not recruiting
• Conditions: Multiple Myeloma; Lymphoma, Non-Hodgkin's
• Intervention / Treatment: Drug: Dexamethasone Oral; Drug: cemsidomide

• Study Type: Interventional
• Enrollment (Estimated): 224
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85054
      • Mayo Clinic
  • California
    • San Francisco, California, United States, 94143
      • University of California-San Francisco
  • Colorado
    • Denver, Colorado, United States, 80218
      • Colorado Blood Cancer Institute (Sarah Cannon Research Institute)
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University Hospital
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana-Farber Cancer Institute
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Washington University School of St. Louis
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
    • New York, New York, United States, 10029
      • Mt Sinai Medical Center
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Tennessee Oncology (Sarah Cannon Research Institute)
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

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

Description

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. ECOG Performance Status ≤2.

4. Have histologically-confirmed NHL or MM that has relapsed from or is refractory to prior therapy, and should not be candidates for regimens known to provide clinical benefit or should have refused such treatment options

   • MM subjects must have:
   • Measurable disease at baseline defined as:

1. Serum M protein ≥0.5g/dL; or
2. Urine M protein ≥200mg/24-hour; or
3. For subjects without measurable serum or urine M protein, serum FLC >100 mg/L and an abnormal (κ/λ) ratio

4. For subjects with (IgA), myeloma whose disease can only be reliably measured by quantitative immunoglobulin measurement, a serum IgA level ≥ 0.50g/dL.

   - Received at least 3 prior treatment regimens including lenalidomide, pomalidomide, a proteasome inhibitor, a glucocorticoid and an anti-CD38 antibody.

   - Refractory to, or had documented disease progression within 60 days from the last dose of their prior MM treatment (or, if the last MM therapy was with CAR-T cells, documented disease progression any time after administration).

   - NHL subjects must have:

   • Documented diagnosis of NHL and measurable disease defined by measurable disease (consistent with Lugano classification)
   • 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 or refused treatment with any standard of care therapies known to provide clinical benefit.

5. In Phase 2, only subjects with the following indications will be eligible for the appropriate expansion arm:

   • Relapsed/refractory MM (as defined in Phase 1 of the study).
   • Relapsed/refractory T-cell NHL including: PTCL, PTCL-NOS, AITL and ALCL with relapsed refractory disease following 1 prior line of therapy containing alkylator-based chemotherapy will be included. Subjects with ALCL must have had prior exposure to anti CD30 antibody as part of their prior treatment regimen.
6. Have provided archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion (lymph node or extra-nodal infiltration of a tissue for NHL subjects, bone marrow aspirate and biopsy for MM subjects) and for Adult T-cell leukemia/lymphoma (ATLL) subjects [if applicable], not previously irradiated.

7. Subjects need to have adequate organ function defined as follows to include:

   - ANC ≥1.0 x 109/L

   - Platelets ≥75,000 cells/µL

   - Hemoglobin ≥8.0 g/dL

   - ALT and AST ≤3.0 x upper limit of normal (ULN); except for subjects who have tumor infiltration of the liver, where ALT or AST ≤5 x ULN.

   - Total bilirubin ≤1.5 x ULN (unless due to Gilbert's syndrome).

   - CrCl ≥40 mL/min

   • International normalized ratio (INR) <1.5 x ULN and aPTT <1.5 x ULN (subject receiving anticoagulant therapy must be on a stable regimen)

8. Female subjects may not be pregnant or intend to become pregnant, may not breastfeed or intend to breastfeed, or donate ova, and must satisfy one of the following conditions:

   - A woman of childbearing potential (WOCBP) must agree to use highly effective contraception during study participation and 30 days after the completion of study treatment.

   - A woman on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the contraception methods specified if they wish to continue their HRT during the study

   - A woman of non-childbearing potential (i.e., physiologically incapable of becoming pregnant) or postmenopausal

9. A male subject must agree to use a condom when having intercourse with a person of child bearing potential during the treatment period and for at least 30 days after the last dose of study treatment.
10. Males must refrain from donating sperm during the treatment period and for 30 days after the last dose of study treatment.
11. Subjects must refrain from donating blood during study treatment and for 30 days after discontinuation.

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
   • B-cell or T-cell prolymphocytic leukemia
   • Chronic lymphocytic lymphoma/small cell lymphoma
   • Richter's transformation
   • Burkitt lymphoma
   • Myelodysplastic syndrome
5. Have received prior CC92480 (mezigdomide) during the subjects most recent line of therapy
6. Subjects with a peripheral neuropathy ≥ Grade 2 at screening.

7. Clinically significant impaired cardiac function or clinically significant cardiac disease, including any of the following:

   • Clinically significant and/or uncontrolled heart disease such as congestive heart failure requiring treatment (NYHA ≥Grade 2), uncontrolled hypertension, or clinically significant arrhythmia.
   • Interval corrected according to Friderica's correction (QTcF) >480 msec on screening ECG.
   • Acute myocardial infarction or unstable angina pectoris within 6 months prior to study entry.
8. Thromboembolic event occurring within 3 months of the first dose of cemsidomide. Enrolled subjects must have a risk-based prophylaxis for venous thromboembolism.
9. Known malignancy other than study indication that has progressed or has required treatment within the past 3 years.
10. Major surgery within 2 weeks of the first dose of study treatment.
11. Presence of ≥Grade 2 toxicity (CTCAE v5.0) due to prior cancer therapy.
12. Received live, attenuated vaccine within four weeks of first dose.
13. Known history of human immunodeficiency virus (HIV) infection. No HIV testing is required unless mandated by local health authority.
14. Any Subject with a known history of, or considered at risk for, Hepatitis B infection must be tested. Subjects will be excluded if Hepatitis B surface antigen (HBS-Ag) is detected
15. Any Subject with a known history or risk of Hepatitis C virus must test negative for anti-HCV antibodies. If anti-HCV antibodies are present or there is prior history of HCV treatment, HCV RNA must be undetectable.
16. Uncontrolled active systemic infection or any life-threatening illness, medical condition, or organ system dysfunction which, in the investigator's opinion, could compromise the subject's safety or put the study outcomes at undue risk.
17. Concurrent administration of strong CYP3A modulators (inducers or inhibitors, including certain foods) and inhibitors of MDR1 (p-glycoprotein) and BCRP. Strong CYP3A inhibitors and inhibitors of MDR1 and BCFP must be discontinued 5 half-lives before the first dose of study drug, and strong CYP3A inducers must be discontinued 14 days prior to the first dose of study drug.
18. Is currently participating in, or has participated in, a study of an investigational agent, or has used an investigational treatment within ≤ 5 half-lives or within 4 weeks (whichever is shorter) prior to the first dose of study treatment.
19. Inability or difficulty swallowing capsules, or tablets (as available), malabsorption syndrome, or any disease or medical condition significantly affecting gastrointestinal function.
20. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound results of the study, interfere with the subject's participation for full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
21. Has a known psychiatric or substance abuse disorder that would interfere with cooperating with requirements of the study.
22. Previously identified hypersensitivity to components of the study treatment or excipients.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase 1: Arm A - cemsidomide; Participants with r/r NHL or r/r MM will be treated with oral cemsidomide as a single agent administered at different dosages and dosing schedules.	Drug: cemsidomide; oral cemsidomide; Other Names: CFT7455
Experimental: Phase 1: Arm B1 - cemsidomide; Participants with r/r MM will be treated with escalating doses of oral cemsidomide as a single agent administered at different dosages and dosing schedules in each cohort, until the determination of maximum tolerated dose (MTD)/recommended Phase 2 dose (RP2D) or Sponsor discretion.	Drug: cemsidomide; oral cemsidomide; Other Names: CFT7455
Experimental: Phase 1: Arm B2 - cemsidomide in combination with dexamethasone; Participants with r/r MM will be treated with escalating doses of oral cemsidomide in combination with a fixed dose of oral dexamethasone in each cohort	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]; Drug: cemsidomide; oral cemsidomide; Other Names: CFT7455
Experimental: Phase 1: Arm C - cemsidomide; Participants with r/r NHL will be treated with escalating doses of oral cemsidomide single agent administered according to different dosing schedules in each cohort	Drug: cemsidomide; oral cemsidomide; Other Names: CFT7455
Experimental: Phase 2: Arm 1 - cemsidomide; Participants with r/r MM will be treated with oral cemsidomide single agent	Drug: cemsidomide; oral cemsidomide; Other Names: CFT7455
Experimental: Phase 2: Arm 2 - cemsidomide in combination with dexamethasone; Participants with r/r MM treated with oral cemsidomide in combination with oral dexamethasone	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]; Drug: cemsidomide; oral cemsidomide; Other Names: CFT7455
Experimental: Phase 2: Arm 3 - CFT7455; Participants with r/r peripheral T-cell lymphoma (PTCL) treated with oral cemsidomide single agent	Drug: cemsidomide; oral cemsidomide; Other Names: CFT7455

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 1: Safety and tolerability of cemsidomide	Percent of subjects with adverse events (AEs) with cemsidomide as a single agent	Baseline through 30 days after the last dose of study treatment
Phase 1: Safety and tolerability of cemsidomide in combination with dexamethasone	Percent of subjects with AEs with cemsidomide in combination with dexamethasone	Baseline through 30 days after the last dose of study treatment
Phase 1: Maximum tolerated dose (MTD) or recommended Phase 2 dose (RP2D) for cemsidomide	Percent of subjects with dose-limiting toxicities (DLTs) with cemsidomide as a single agent	Days 1-28
Phase 1: MTD or recommended RP2D for cemsidomide in combination with dexamethasone	Percent of subjects with DLTs with cemsidomide in combination with dexamethasone	Days 1-28
Phase 2: Antitumor activity of cemsidomide as a single agent	Overall Response Rate (ORR) based on Best Overall Response (BOR), Duration of Response (DOR), and Progression Free Survival (PFS) of cemsidomide	Baseline through 6 months after the last dose of study treatment, or until disease progression, whichever occurs first
Phase 2: Antitumor activity of cemsidomide in combination with dexamethasone	ORR based on BOR, DOR, and PFS of cemsidomide in combination with dexamethasone in subjects with MM based on International Myeloma Working Group (IMWG) criteria	Baseline through 6 months after the last dose of study treatment, or until disease progression, whichever occurs first

Collaborators and Investigators

• Sponsor: C4 Therapeutics, Inc.
• Investigators: Study Director: Adam Crystal, MD, C4 Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): April 27, 2021
• Primary Completion (Estimated): September 30, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: February 12, 2021
• First Submitted That Met QC Criteria: February 12, 2021
• First Posted (Actual): February 16, 2021

Study Record Updates

• Last Update Posted (Actual): March 25, 2026
• Last Update Submitted That Met QC Criteria: March 24, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Multiple Myeloma; Relapsed; Refractory; Lymphoma, Non-Hodgkin's; CFT7455
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Neoplasms; Disease Attributes; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma; Neoplasms, Plasma Cell; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Pathological Conditions, Signs and Symptoms; Hemic and Lymphatic Diseases; Recurrence; Multiple Myeloma; Lymphoma, Non-Hodgkin; Polycyclic Compounds; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Steroids, Fluorinated; Pregnadienetriols; Dexamethasone
• Other Study ID Numbers: CFT7455-1101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No