for people ages 18 years and up (full criteria)
study started
estimated completion
Principal Investigator
by Antoni Ribas, MD (ucla)



This study will evaluate the safety, tolerability, and efficacy of oral KPT-9274 for the treatment of patients with advanced solid malignancies or non-Hodgkin's lymphoma (NHL). Currently enrolling melanoma patients in combination with nivolumab, only.

Official Title

A Phase 1 Open-Label Study of the Safety, Tolerability and Efficacy of KPT-9274, a Dual Inhibitor of PAK4 and NAMPT, in Patients With Advanced Solid Malignancies or Non-Hodgkin's Lymphoma


This is a first-in-human, multi-center, open-label clinical study with separate Dose Escalation and Expansion Phases to assess preliminary safety, tolerability, and efficacy of KPT-9274, a dual inhibitor of PAK4 and NAMPT, in patients with advanced solid malignancies (including sarcoma, colon, lung, melanoma, etc.) or NHL for which all standard therapeutic options considered useful by the investigator have been exhausted.


Solid Tumors NHL PAK4 KPT-9274 Karyopharm NAMPT Melanoma Neoplasms Niacin Nivolumab Niacin ER KPT-9274 & Niacin Extended Release (ER) KPT-9274 + Nivolumab


You can join if…

Open to people ages 18 years and up

Participants must meet all of the following inclusion criteria to be eligible to enroll in the Part C of this study.

  1. Should have unresectable advanced, recurrent or metastatic melanoma and must have objective and measurable melanoma by RECIST 1.1 after disease progression on a prior anti-PD-1 or anti-PD-L1 therapy.
  2. ECOG performance status of ≤ 2.
  3. Life expectancy of ≥ 3 months.
  4. Adequate hepatic function:
  5. Total bilirubin < 1.5 times the ULN (except participants with Gilbert's syndrome [hereditary indirect hyperbilirubinemia] who must have a total bilirubin of ≤ 3 times ULN),
  6. AST and ALT ≤ 2.5 times ULN (except participants with known liver involvement of their advanced solid malignancy who must have an AST and ALT ≤ 5.0 times ULN).
  7. Adequate renal function:
  8. Estimated creatinine clearance of ≥ 60 mL/min, calculated using the formula of Cockroft and Gault (140-Age) Mass (kg)/(72 creatinine mg/dL); multiply by 0.85 if female.
  9. Adequate hematopoietic function:
  10. Total WBC count ≥ 1500/mm³, ANC ≥ 1000/mm³, Hb ≥ 10.0 g/dL, platelet count ≥ 100,000/mm³

You CAN'T join if...

Participants meeting any of the following exclusion criteria are not eligible to enroll in this study.

  1. ≤ 2 weeks since the last prior therapeutic regimen for melanoma. Palliative steroids for disease related symptoms < 7 days prior to C1D1, unless physiologic doses of steroids are used.
  2. Have not recovered or stabilized (Gr 1 or to their baseline for non-hematologic toxicities, ≤ Gr 2 or to their baseline for hematologic toxicities) from toxicities related to their previous treatment except for alopecia.
  3. Untreated CNS disease or leptomeningeal involvement are excluded. Participants without active brain or leptomeningeal metastases after prior treatment with local therapies are eligible provided that the treatment had been done ≥ 2 weeks prior to enrollment.
  4. Active infection with completion of therapeutic antibiotics, antivirals, or antifungals within one week prior to C1D1. Prophylactic antibiotics, antivirals or antifungals are permitted.
  5. Significantly diseased or obstructed gastrointestinal tract or uncontrolled vomiting or diarrhea that could interfere with the absorption of KPT-9274.
  6. Active peptic ulcer disease or other active gastrointestinal bleeds.
  7. Requiring treatment with corticosteroids at doses higher than substitute therapy (> 10 mg prednisone), are unstable with substitute hormonal therapy, or are deemed to be likely to re-occur by the treating physician when administered nivolumab.


  • UCLA Health accepting new patients
    Los Angeles California 90024 United States
  • University of Colorado Cancer Center completed
    Aurora Colorado 80045 United States

Lead Scientist at UC Health

  • Antoni Ribas, MD (ucla)
    Professor, Medicine. Authored (or co-authored) 343 research publications.


accepting new patients
Start Date
Completion Date
Karyopharm Therapeutics Inc
Phase 1
Study Type
Last Updated