Ensayos clínicos

Inclusion Criteria:

• Be willing and able to provide signed informed consent for the trial.
• Age ≥ 18 years at the time of signed consent.
• Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2.
• Have histologically-confirmed NHL or MM that is relapsed/refractory 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 ≥ 0.5  sPEP; or
  • ≥ 200mg/24-hour urine collection by uPEP; or
  • Serum 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 ≥ 0.50 g/dL.
• In addition, prior treatments for 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.
  • Note: If the most recent prior therapy was BCMA CAR-T, there is no time dependency from the last infusion until documented progression.

NHL:

• Subjects must have documented diagnosis of NHL and measurable disease (consistent with Lugano classification) defined by:
  • Either fluorodeoxyglucose (FDG)-avidity on positron emission tomography (PET)-computed tomography (CT) using the 5-point scale or measurable disease defined as at least one lesion that can be accurately measured in at least two dimensions with contrast enhanced CT scan. Minimum measurement must be ≥ 15 mm in the longest diameter. This baseline scan would occur within 6 weeks of their projected C1D1 visit.
• 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 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 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:
  • Absolute neutrophil count (ANC) ≥ 1.0 x 10^9 /L independent of growth factor support for at least 7 days prior to first dose for G-CSF, and for at least 14 days prior to first dose if using pegfilgrastim;
  • Platelets ≥ 75,000 cells/µL independent of transfusion support for at least 7 days prior to first dose;
  • Hemoglobin ≥ 8.0 g/dL independent of transfusion support for at least 7 days prior to first dose;
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (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 (Cockcroft-Gault equation, or per institutional standard, or measured);
  • Prothrombin time (PT)/international normalized ratio (INR) < 1.5 x ULN and activated partial thromboplastin time (aPTT) < 1.5 x ULN (unless the subject is receiving anticoagulant therapy and INR and PTT/aPTT is within therapeutic range of intended use of anticoagulants).
• Note: Subjects receiving therapy for a thromboembolic event that occurred ≥ 3 months prior to enrollment are eligible for participation on the study if they are stable on a regimen of anticoagulation with a warfarin, low-molecular weight heparin or any other approved therapeutic anticoagulation.
• 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 <4 0 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 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.
  • Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the contraception methods specified 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.
  • For most forms of HRT, at least 2-4 weeks will elapse between the cessation of therapy and the blood draw, with the exact interval dependent on the type and dosage of HRT. Following confirmation of their post-menopausal status, the subject can resume use of HRT during the study without use of a contraceptive method.
  • 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.
  • Note: Women are considered postmenopausal and not of childbearing potential if they have had 12 months of natural amenorrhea with an appropriate clinical profile or have had either surgical bilateral oophorectomy or tubal ligation at least 6 weeks prior to the first dose of study treatment.
• A male participant must have either had a prior vasectomy or agree to use a condom during the treatment period and for at least 30 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 myeloma or lymphoma in the central nervous system (CNS).
• Has received prior radiotherapy within 2 weeks of start of study treatment.
• Subjects with active pneumonitis.
• Subjects with any of the following:
  • Non-secretory or oligosecretory multiple myeloma;
  • 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 3 years.
  • Note 1: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g., breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded.
  • Note 2: Clinically significant and unequivocal myelodysplastic syndrome (MDS) is excluded.
• 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, MCSF) ≤ 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 4 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 (inducers or inhibitors).
  • Note: If a subject can be switched to a similar agent which is not a strong CYP3A modulator or is a weak CYP3A modulator they may be permitted to enroll in the study.
• 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.
• Study enrollment has been closed for one or all respective cohorts or the study has been terminated by the Sponsor.

Note: Other protocol defined Inclusion/Exclusion Criteria may apply.

Eligibility last updated 8/23/23. Questions regarding updates should be directed to the study team contact.