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 (in MM subjects only).

Eligibility

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 or cytologically-confirmed NHL or MM that is r/r disease and must not be candidates for regimens known to provide clinical benefit
5. MM subject must have a documented diagnosis of MM and measurable disease at enrollment. Measurable disease is defined as:
6. Serum M protein =0.5g/dL; or
7. Urine M protein =200mg/24-hour; or
8. Serum Free Light Chain >100 mg/L involved light chain and an abnormal (?/?) ratio in subjects without measurable serum or urine M-protein or
9. For subjects with (IgA), myeloma whose disease can only be reliably measured by quantitative immunoglobulin measurement, a serum IgA level = 0.50g/dL.
10. MM subjects must have received at least 3 prior treatment regimens including lenalidomide, pomalidomide, a proteasome inhibitor, a glucocorticoid and an anti-CD38 antibody
11. 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.
12. NHL subjects must have documented diagnosis of NHL and measurable disease defined by measurable disease (consistent with Lugano classification)
13. NHL subjects must have received the following regarding prior therapy:
14. 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.
15. Mantle Cell Lymphoma: =2 lines of therapy, including CD20 antibody and alkylator chemotherapy, and a Bruton's tyrosine kinase (BTK) inhibitor.
16. Follicular Lymphoma: =2 lines of therapy, including CD20 antibody therapy and alkylator chemotherapy.
17. 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).
18. 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.
19. In Phase 2, only subjects with the following indications will be eligible for the appropriate expansion arm:
20. Relapsed/refractory MM (as defined in Phase 1 of the study).
21. 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.
22. 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.
23. 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.
24. Subjects need to have adequate organ function defined as follows to include:
25. ANC =1.0 x 109/L independent of growth factor support
26. Platelets =75,000 cells/µL independent of transfusion support
27. Hemoglobin =8.0 g/dL independent of transfusion support
28. 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.
29. Total bilirubin =1.5 x ULN (unless due to Gilbert's syndrome).
30. CrCl =40 mL/min
31. PT/INR <1.5 x ULN and aPTT <1.5 x ULN (unless the subject is receiving anticoagulant therapy)
32. A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:
33. A woman of non-childbearing potential (i.e., physiologically incapable of becoming pregnant) or postmenopausal
34. 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:
35. Have two negative pregnancy tests verified by the investigator prior to the first dose of CFT7455.
36. Serum pregnancy test within 10 to 14 days prior to C1D1.
37. Serum/urine pregnancy test within 24 hours prior to first dose.
38. Agree to having ongoing pregnancy tests during the study and after discontinuation of the study.
39. Highly effective contraception methods include:
40. Female sterilization, total hysterectomy, or tubal ligation at least 6 weeks before taking study treatment.
41. For male partners of female subjects: Male sterilization (at least 6 months prior to screening).
42. 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.
43. 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.
44. Males must refrain from donating sperm while on CFT7455 and for 30 days after discontinuation.
45. Females must refrain from donating ova while on CFT7455 and for 30 days after discontinuation.
46. Subjects must refrain from donating blood during study treatment and for 30 days after discontinuation.