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

Sponsor

C4 Therapeutics, Inc. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04756726

Collaborator

(none)

158

Enrollment

Locations

Arms

43.4

Anticipated Duration (Months)

11.3

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

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

Anticipated 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 :

Apr 27, 2021

Anticipated Primary Completion Date :

Sep 7, 2024

Anticipated Study Completion Date :

Dec 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

Phase 1: Safety and tolerability of CFT7455 [Days 1-28]
Percent of subjects with adverse events (AEs) with CFT7455 as a single agent
Phase 1: Safety and tolerability of CFT7455 for CFT7455 in combination with dexamethasone [Days 1-28]
Percent of subjects with AEs with CFT7455 in combination with dexamethasone
Phase 1: Maximum tolerated dose (MTD) or recommended Phase 2 dose (RP2D) for CFT7455 [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
Phase 1: MTD or recommended RP2D for CFT7455 in combination with dexamethasone [Baseline through 3 months after the last dose of study treatment]
Percent of subjects with DLTs with CFT7455 in combination with dexamethasone
Phase 2: Antitumor activity of CFT7455 [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
Phase 2: Antitumor activity of CFT7455 in combination with dexamethasone [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

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Be willing and able to provide signed informed consent for the trial.
Age ≥18 years at the time of signed consent.
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.
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.

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.

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.
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.

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.

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:

Presence of central nervous system (CNS) disease.
Has received prior radiotherapy within 2 weeks of start of study treatment.
Have active pneumonitis.
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

Subjects with a peripheral neuropathy ≥ Grade 2.
Known malignancy other than study indication that is progressing or has required treatment within the past three years.
Received live, attenuated vaccine within four weeks of first dose.
Known history of human immunodeficiency virus (HIV) infection. No HIV testing is required unless mandated by local health authority.
Subjects with positive test for Hepatitis B surface (HBS-Ag) or Hepatitis B core (HBc) antigen.
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.
Concurrent administration of strong CYP3A modulators.
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.
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

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic	Phoenix	Arizona	United States	85054
2	University of California-San Francisco	San Francisco	California	United States	94143
3	Colorado Blood Cancer Institute (Sarah Cannon Research Institute)	Denver	Colorado	United States	80218
4	Mayo Clinic	Jacksonville	Florida	United States	32224
5	Emory University Hospital	Atlanta	Georgia	United States	30322
6	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
7	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02215
8	Mayo Clinic	Rochester	Minnesota	United States	55905
9	Washington University School of St. Louis	Saint Louis	Missouri	United States	63110
10	Mt Sinai Medical Center	New York	New York	United States	10029
11	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
12	Levine Cancer Institute - Charlotte	Charlotte	North Carolina	United States	28204
13	Tennessee Oncology (Sarah Cannon Research Institute)	Nashville	Tennessee	United States	37203
14	Medical College of Wisconsin	Milwaukee	Wisconsin	United States	53226