Ensayos clínicos

Inclusion Criteria:

• Voluntarily provide informed consent prior to initiation of study specific activities.
• ≥ 18 years of age.
• Eastern Cooperative Oncology Group (ECOG) score ≤ 1.
• Patients must have a confirmed diagnosis of RRMM (as per IMWG):
  • Patients must have received at least 3 prior lines of therapy as defined by IMWG, including a PI, an IMiD, and an anti-CD38 antibody;
  • 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;
  • For expansion cohorts in Part B only: Have t(4;14) confirmed by standard of care FISH testing or GOF mutation in MMSET confirmed by local sequencing test.
• Measurable disease, including at least 1 of the following criteria:
  • Serum M protein (detected by serum protein electrophoresis [SPEP]) ≥ 0.50 g/dL;
    • For patients with immunoglobulin class A (IgA) myeloma whose disease can only be reliably measured by quantitative immunoglobulin measurement, a serum IgA ≥ 0.50 g/dL (IgA will similarly be used for response).
  • Urine M protein (detected by urine protein electrophoresis [UPEP]) ≥ 200 mg/24 h;
  • Serum free light chain (sFLC) involved light chain ≥ 10 mg/dL (100 mg/L) provided sFLC ratio is abnormal;
  • ≥ 1 extramedullary lesion on imaging, including ≥ 1 lesion that is ≥ 1 cm in size and able to be followed by imaging assessments (Dose Escalation Only);
  • Bone marrow plasma cells ≥ 10% (Dose Escalation Only).
• Recovery to Grade ≤ 1 for any nonhematologic toxicities due to prior therapy, excluding alopecia or Grade 2 neuropathy.
• Ability and willingness to adhere to study visit schedule and protocol requirements.

Exclusion Criteria:

• Treatment with the following therapies in the specified time period:
  • Radiation, chemotherapy, immunotherapy, or any other anticancer therapy ≤ 2 weeks prior to C1D1;
  • Cellular therapies (eg, chimeric antigen receptor T-cell) ≤ 8 weeks prior to C1D1;
  • < 100 days post autologous transplant (prior to first dose);
  • ≤ 6 months post allogenic transplant prior to C1D1 or if > than 6 months from allogenic transplant, no active graft-versus-host disease requiring treatment;
  • Major surgery ≤ 4 weeks from C1D1.
• History of or 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.
• Active central nervous system (CNS) disease: patients with previously treated stable CNS disease are eligible.
• Inadequate bone marrow function defined by:
  • ANC < 1000 cells/mm^3;
  • Platelets (PLT) < 75,000 cells/mm^3;
  • Hemoglobin < 8 g/dL (may be transfused provided no evidence of active bleeding).
• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2.5 × upper limit of normal (ULN).
• Direct bilirubin > 1.5 × ULN, > 2 × ULN for patients with documented Gilbert’s syndrome.
• Prothrombin time (PT) or partial thromboplastin time (PTT) international normalized ratio (INR) > 1.5 × ULN, OR INR > 1.5 × ULN or within target range if on prophylactic anticoagulation.
• Creatinine clearance < 50 mL/min by Cockcroft-Gault formula.
• Active, ongoing, or uncontrolled systemic viral, bacterial, or fungal infection. Prophylactic medications, antimicrobials or antiretroviral therapies are permitted provided the agents are not prohibited per Section 6.4.6 and Appendix 1:
  • HIV-positive patients with CD4+ T-cell counts < 350 cells/μL or not on a stable antiretroviral regimen for > 4 weeks with a viral load > 400 copies/mL prior to enrollment may not be enrolled;
  • Hepatitis C virus (HCV)-positive patients who have not completed curative antiviral treatment and have a quantifiable viral load may not be enrolled;
  • Hepatitis B surface antigen (HBs-AG)-positive and hepatitis B core antigen (anti-HBc)-positive patients may be enrolled following a discussion with the Medical Monitor to discuss anti-hepatitis B virus (HBV) prophylaxis. Patients with chronic HBV infection should complete an anti-HBV therapy regimen with follow-up assessment for response and tolerability prior to initiating study medication.
• Use of prohibited medications, including acid reducing agents and strong inhibitors or inducers of CYP3A4 within 14 days or 5 half-lives prior to starting KTX-1001.
• Uncontrolled thromboembolic events or recent severe hemorrhage that, in the opinion of the Investigator or Medical Monitor would pose a risk to patient safety or interfere with the study evaluation, procedures or completion.
• Any history of pulmonary embolism or deep vein thrombosis (DVT) within 1 month of enrollment. Therapeutic dosing of anticoagulants (eg, warfarin, low molecular weight heparin, Factor Xa inhibitors) is allowed for history of DVT if > 3 months from time of enrollment.
• Active, unstable cardiovascular function; presence of any of the following:
  • Symptomatic ischemia;
  • Uncontrolled clinically significant conduction abnormalities (eg, patients with ventricular tachycardia on antiarrhythmics are excluded; patients with first degree atrioventricular or asymptomatic left anterior fascicular block/right bundle branch block will not be excluded);
  • Congestive heart failure or New York Heart Association Class ≥ 3;
  • Myocardial infarction within 3 months prior to C1D1;
  • Uncontrolled hypertension f. QTc > 470 ms.
• Active malignancy not related to myeloma that has required therapy in the last 2 years prior to enrollment or is not in complete remission. Exceptions to these criteria include successfully treated nonmetastatic basal cell or squamous cell skin carcinoma, or prostate cancer that does not require therapy. Other similar malignant conditions may be discussed with and permitted by the Medical Monitor.
• Malabsorption syndrome or other condition affecting oral absorption.
• Men and women of reproductive potential who are unwilling to practice acceptable methods of effective birth control while on study through 6 months (women) or 3 months (men) after receiving the last dose of study drug. Acceptable methods of effective birth control include sexual abstinence (refraining from heterosexual intercourse; men, women); vasectomy; tubal ligation; or a condom with spermicide (men) in combination with barrier methods, hormonal birth control or intrauterine device (women):
  • Pregnancy, or females planning on becoming pregnant while on study or through 6 months after last study drug administration; or females who are lactating/breast feeding or who plan to breastfeed while on study through 6 months after last study drug administration;
  • Male patients must refrain from sperm donation, or attempt to conceive from study drug administration until 3 months after last dose of study drug.
• History or evidence of any other clinically significant disorder, condition, or disease (except for those outlined above) that, in the opinion of the Investigator or Medical Monitor would pose a risk to patient safety or interfere with the study evaluation, procedures or completion, including inability to find alternative concomitant medications that may be potential risk for drug-drug interaction (DDI).

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

Eligibility last updated 1/25/24. Questions regarding updates should be directed to the study team contact.