Summary

Eligibility
for people ages 18 years and up (full criteria)
Location
at UCLA
Dates
study started
estimated completion
Principal Investigator
Antoni Ribas, MD (ucla)

Description

Summary

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).

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

Details

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.

Keywords

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

Eligibility

You can join if…

Open to people ages 18 years and up

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

  1. 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 patients 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 patients 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...

Patients 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. In specific cases, patients with Gr 2 non-hematologic toxicities will be allowed following approval by the Karyopharm medical monitor.
  3. Untreated CNS disease or leptomeningeal involvement are excluded. Patients 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.

Locations

  • UCLA Health not yet accepting 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) 315 research publications.

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Karyopharm Therapeutics Inc
ID
NCT02702492
Phase
Phase 1
Study Type
Interventional
Last Updated