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

C

C4 Therapeutics

Status and phase

Enrolling
Phase 2
Phase 1

Conditions

Lymphoma, Non-Hodgkin's
Multiple Myeloma

Treatments

Drug: Dexamethasone Oral
Drug: CFT7455

Study type

Interventional

Funder types

Industry

Identifiers

NCT04756726
CFT7455-1101

Details and patient eligibility

About

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 (in MM subjects only).

Enrollment

158 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No 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.
  • ECOG Performance Status ≤2.

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

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

  • Serum M protein ≥0.5g/dL; or
  • Urine M protein ≥200mg/24-hour; or
  • Serum Free Light Chain >100 mg/L involved light chain and an abnormal (κ/λ) ratio in subjects without measurable serum or urine M-protein or
  • For subjects with (IgA), myeloma whose disease can only be reliably measured by quantitative immunoglobulin measurement, a serum IgA level ≥ 0.50g/dL.
  • MM subjects must have received at least 3 prior treatment regimens including lenalidomide, pomalidomide, a proteasome inhibitor, a glucocorticoid and an anti-CD38 antibody
  • 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)

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.

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 MCL (defined as above). Subjects must have received at least ≥2 prior treatment regimens containing an anti-CD20 antibody and alkylator chemotherapy and a regimen containing a BTK inhibitor.
  • 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.
  • Have provided archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion (lymph node for NHL subjects, bone marrow aspirate and biopsy for MM subjects) not previously irradiated.

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

  • ANC ≥1.0 x 109/L independent of growth factor support
  • Platelets ≥75,000 cells/µL independent of transfusion support
  • Hemoglobin ≥8.0 g/dL independent of transfusion support
  • 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
  • PT/INR <1.5 x ULN and aPTT <1.5 x ULN (unless the subject is receiving anticoagulant therapy)

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) or postmenopausal

A woman of childbearing potential (WOCBP), defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during study treatment and for 30 days for females and 30 days for males after the last dose of study treatment, must:

  • Have two negative pregnancy tests verified by the investigator prior to the first dose of CFT7455.
  • Serum pregnancy test within 10 to 14 days prior to C1D1.
  • Serum/urine pregnancy test within 24 hours prior to first dose.
  • Agree to having ongoing pregnancy tests during the study and after discontinuation of the study.

Highly effective contraception methods include:

  • Female sterilization, total hysterectomy, or tubal ligation at least 6 weeks before taking study treatment.
  • For male partners of female subjects: Male sterilization (at least 6 months prior to screening).
  • Use of highly effective contraception methods as indicated (abstinence) without interruption at least 14 days prior to first dose, during the conduct of the study including periods of dose interruptions of the study treatment, and for 30 days for females and 30 days for male after discontinuation of CFT7455.
  • 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.
  • Males must refrain from donating sperm while on CFT7455 and for 30 days after discontinuation.
  • Females must refrain from donating ova while on CFT7455 and for 30 days after discontinuation.
  • Subjects must refrain from donating blood during study treatment and for 30 days after discontinuation.

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
  • B-cell or T-cell prolymphocytic leukemia
  • Chronic lymphocytic lymphoma/small cell lymphoma
  • Richter's transformation
  • Burkitt lymphoma
  • Have received prior CC92480 as the most recent therapy
  • Subjects with a peripheral neuropathy ≥ Grade 2.

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.
  • Corrected QT (QTcF) >480 msec for males and females using Fridericia's correction on screening ECG.
  • Acute myocardial infarction or unstable angina pectoris within 6 months prior to study entry.
  • VTE occurring within 3 months of the first dose in Cycle 1 onto the study or a subject who is unable or unwilling to undergo protocol required venous thromboembolism prophylaxis.
  • Known malignancy other than study indication that is progressing or has required treatment within the past three years.
  • Major surgery within 2 weeks of the first dose of study treatment.
  • Presence of ≥Grade 2 toxicity (CTCAE v5.0) due to prior cancer therapy.
  • Initiation of hematopoietic colony-stimulating growth factors (e.g., G-CSF, GMCSF, M-CSF) ≤1 week prior to start of study treatment. An erythroid stimulating agent is allowed if it was initiated at least 2 weeks prior to the first dose of study treatment.
  • 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.
  • Any Subject with a known history or risk of Hepatitis B must be tested for HBV. Subjects will be excluded if there is a reactive Hepatitis B surface antigen (HBS-Ag) or Hepatitis B core antibody (anti-HBc total).
  • Any Subject with a known history or risk of Hepatitis C must be tested for HCV. 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.
  • 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.
  • Concurrent administration of strong CYP3A modulators.
  • 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.
  • Inability or difficulty swallowing capsules, or tablets (as available), malabsorption syndrome, or any disease or medical condition significantly affecting gastrointestinal function.
  • 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.
  • Has a known psychiatric or substance abuse disorder that would interfere with cooperating with requirements of the study.
  • Is pregnant, breastfeeding, or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 30 days after the last dose of study treatment.
  • Previously identified hypersensitivity to components of the study treatment or excipients.

Trial design

Primary purpose

Treatment

Allocation

Non-Randomized

Interventional model

Sequential Assignment

Masking

None (Open label)

158 participants in 8 patient groups

Phase 1: Arm A - CFT7455
Experimental group
Description:
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
Treatment:
Drug: CFT7455
Phase 1: Arm B1 - CFT7455
Experimental group
Description:
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)
Treatment:
Drug: CFT7455
Phase 1: Arm B2 - CFT7455 in combination with dexamethasone
Experimental group
Description:
Participants with r/r MM will be treated with oral CFT7455 in combination with a fixed dose of oral dexamethasone in each cohort
Treatment:
Drug: CFT7455
Drug: Dexamethasone Oral
Phase 1: Arm C - CFT7455
Experimental group
Description:
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
Treatment:
Drug: CFT7455
Phase 2: Arm 1 - CFT7455
Experimental group
Description:
Participants with r/r MM will be treated with oral CFT7455
Treatment:
Drug: CFT7455
Phase 2: Arm 2 - CFT7455 in combination with dexamethasone
Experimental group
Description:
Participants with r/r MM treated with oral CFT7455 in combination with oral dexamethasone
Treatment:
Drug: CFT7455
Drug: Dexamethasone Oral
Phase 2: Arm 3 - CFT7455
Experimental group
Description:
Participants with r/r mantle cell lymphoma (MCL) treated with oral CFT7455
Treatment:
Drug: CFT7455
Phase 2: Arm 4 - CFT7455
Experimental group
Description:
Participants with r/r peripheral T-cell lymphoma (PTCL) treated with oral CFT7455
Treatment:
Drug: CFT7455

Trial contacts and locations

13

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Central trial contact

Study Medical officer

Data sourced from clinicaltrials.gov

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