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
once a day (QD) as a single agent and in combination with dexamethasone.
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
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
- For subjects with immunoglobulin class A (IgA), myeloma whose disease can only be
reliably measured by quantitative immunoglobulin measurement, a serum IgA level ≥
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
- 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
- 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
- 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
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)
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.