A Study of an MMSET Inhibitor in Patients With Relapsed and Refractory Multiple Myeloma

Key Inclusion Criteria for Dose-Expansion:

• ≥ 18 years of age

• ECOG score ≤ 1

• Multiple myeloma (as per IMWG)

• ≥ 3 prior lines of therapy, including a PI, an IMiD, and an anti-CD38 antibody

• Patients must be refractory to their last prior therapy

• Cohorts A1/A2: Patients must have exhausted available therapeutic options that are expected to provide a meaningful clinical benefit, either through disease relapse, treatment refractory disease, intolerance, or refusal of the therapy

• t(4;14) confirmed by standard of care FISH testing

• Measurable disease, including at least 1 of the following criteria:

• Serum M protein ≥ 0.50 g/dL (by SPEP)

• Serum IgA ≥ 0.50 g/dL (IgA myeloma patients)

• Urine M protein ≥ 200 mg/24 h (by UPEP)

• sFLC involved light chain ≥ 10 mg/dL (100 mg/L) (patients with abnormal sFLC ratio)

• Bone marrow plasma cells ≥ 30% (if only criterion for measurability)

• Agreement to enroll into the REMS program (Cohort D- pomalidomide cohort only)

Key Exclusion Criteria for Dose-Expansion:

• Treatment with the following therapies in the specified time period prior to first dose:

• Carfilzomib in the immediate last prior line of therapy for patients enrolled in Cohorts C1 and C2

• Pomalidomide in the immediate last prior line of therapy for patients enrolled in cohort D

• Radiation, chemotherapy, immunotherapy, or any other anticancer therapy ≤ 2 weeks

• Cellular therapies ≤ 8 weeks

• Autologous transplant < 100 days

• Allogenic transplant ≤ 6 months, or > 6 months with active GVHD

• Major surgery ≤ 4 weeks

• Current plasma cell leukemia, POEMS (polyneuropathy, organomegaly, endocrinopathy, and skin changes) syndrome, solitary bone lesion or bone lesions as the only evidence for plasma cell dyscrasia, myelodysplastic syndrome or a myeloproliferative neoplasm or light chain amyloidosis

• MM with extramedullary disease (applies to Cohorts A1 & A2: KTX-1001, C1 & C2: Carfilzomib, and D: Pomalidomide only)

• Active CNS disease

• Inadequate bone marrow function

• Inadequate renal, hepatic, pulmonary, and cardiac function

• Active, ongoing, or uncontrolled systemic viral, bacterial, or fungal infection. Permitted prophylactic medications, antimicrobials or antiretroviral therapies defined in protocol.

• Use of acid reducing agents and strong inhibitors or inducers of CYP3A4 within 14 days or 5 half-lives prior to first dose

• Strong CYP1A2 inhibitors for patients receiving pomalidomide (Cohort D)

• Active malignancy not related to myeloma requiring therapy within < 2 years prior to enrollment, or not in complete remission, with exceptions defined in protocol.