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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Multiple Myeloma, Lymphoma, Non-Hodgkin's

Intervention / Treatment
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* Drug: CFT7455
* Drug: Dexamethasone Oral


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Phase 1: Arm A - CFT7455<br>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<br>* oral CFT7455<br>|
| Experimental: Phase 1: Arm B1 - CFT7455<br>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<br>* oral CFT7455<br>|
| Experimental: Phase 1: Arm B2 - CFT7455 in combination with dexamethasone<br>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<br>* oral CFT7455<br>Drug: Dexamethasone Oral<br>* 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]<br>|
| Experimental: Phase 1: Arm C - CFT7455<br>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<br>* oral CFT7455<br>|
| Experimental: Phase 2: Arm 1 - CFT7455<br>Participants with r/r MM will be treated with oral CFT7455 | Drug: CFT7455<br>* oral CFT7455<br>|
| Experimental: Phase 2: Arm 2 - CFT7455 in combination with dexamethasone<br>Participants with r/r MM treated with oral CFT7455 in combination with oral dexamethasone | Drug: CFT7455<br>* oral CFT7455<br>Drug: Dexamethasone Oral<br>* 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]<br>|
| Experimental: Phase 2: Arm 3 - CFT7455<br>Participants with r/r mantle cell lymphoma (MCL) treated with oral CFT7455 | Drug: CFT7455<br>* oral CFT7455<br>|
| Experimental: Phase 2: Arm 4 - CFT7455<br>Participants with r/r peripheral T-cell lymphoma (PTCL) treated with oral CFT7455 | Drug: CFT7455<br>* oral CFT7455<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase 1: Safety and tolerability of CFT7455 | Percent of subjects with adverse events (AEs) with CFT7455 as a single agent | Days 1-28 | 
| Phase 1: Safety and tolerability of CFT7455 for CFT7455 in combination with dexamethasone | Percent of subjects with AEs with CFT7455 in combination with dexamethasone | Days 1-28 | 
| Phase 1: Maximum tolerated dose (MTD) or recommended Phase 2 dose (RP2D) for CFT7455 | Percent of subjects with dose-limiting toxicities (DLTs) with CFT7455 as a single agent | Baseline through 3 months after the last dose of study treatment | 
| Phase 1: MTD or recommended RP2D for CFT7455 in combination with dexamethasone | Percent of subjects with DLTs with CFT7455 in combination with dexamethasone | Baseline through 3 months after the last dose of study treatment | 
| Phase 2: Antitumor activity of CFT7455 | 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 | Baseline through 6 months after the last dose of study treatment, or until disease progression, whichever occurs first | 
| Phase 2: Antitumor activity of CFT7455 in combination with dexamethasone | 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 | Baseline through 6 months after the last dose of study treatment, or until disease progression, whichever occurs first | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CFT7455, Multiple Myeloma, Lymphoma, Non-Hodgkin's, Relapsed, Refractory