Clinical trial · Interventional
PAK4 and NAMPT in Patients With Solid Malignancies or NHL (PANAMA)
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
NCT02702492CI-TRIAL-00082944PANAMAterminatedPhase 1Results postedClinicalTrials.gov clinicaltrialsProvenance
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Why stopped (as posted): sponsor decision
Summary
Brief summary (as posted)
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).
Conditions
Conditions (2)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| NHL | Non-Hodgkin Lymphoma | ALIAS | 0.90 |
| Solid Tumors | Solid Neoplasm | CURATED_BROADER | 0.80 |
Interventions
Interventions (3)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| KPT-9274 | Drug | — | UNRESOLVED |
| Niacin ER | Drug | — | UNRESOLVED |
| Nivolumab | Drug | Nivolumab | ALIAS |
Design
Arms and outcomes
Arms (13)
- type
- EXPERIMENTAL
- label
- Part A: KPT-9274 10mg
- description
- Participants received a 10 milligrams (mg) of oral tablets of KPT-9274 three times a week every other day during each 28 day cycle.
- interventionNames
- Drug: KPT-9274
- type
- EXPERIMENTAL
- label
- Part A: KPT-9274 20mg
- description
- Participants received a 20mg of oral tablets of KPT-9274 three times a week every other day during each 28 day cycle.
- interventionNames
- Drug: KPT-9274
- type
- EXPERIMENTAL
- label
- Part A: KPT-9274 30mg
- description
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 18 Years
Show eligibility criteria text
Inclusion Criteria: 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: * 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), * 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). 5. Adequate renal function: * 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. 6. Adequate hematopoietic function: * Total WBC count ≥ 1500/mm³, ANC ≥ 1000/mm³, Hb ≥ 10.0 g/dL, platelet count ≥ 100,000/mm³ Exclusion Criteria: 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.
References
Publications (4)
- DERIVEDRazak A, Mahipal A, Diamond JR, Ribas A, Berlin JD, Azmi AS, Mark T, Walker CJ, Chai Y, Kashyap T, Gudi G, Naing A. First-in-Human Phase I Study of KPT-9274, a First-in-Class Dual Inhibitor of PAK4 and NAMPT, in Patients with Advanced Solid Malignancies. Target Oncol. 2026 Mar;21(2):187-198. doi: 10.1007/s11523-026-01206-3. Epub 2026 Mar 13. PMID 41824279
- DERIVEDHan W, Yang Y, Yu F, Li Q, Liu A, Xu W, Li J, Xue X. Design, synthesis and anticancer activity evaluation of 4-(3-1H-indazolyl)amino quinazoline derivatives as PAK4 inhibitors. Bioorg Med Chem. 2023 Nov 15;95:117501. doi: 10.1016/j.bmc.2023.117501. Epub 2023 Oct 13. PMID 37864885
- DERIVEDMpilla GB, Uddin MH, Al-Hallak MN, Aboukameel A, Li Y, Kim SH, Beydoun R, Dyson G, Baloglu E, Senapedis WT, Landesman Y, Wagner KU, Viola NT, El-Rayes BF, Philip PA, Mohammad RM, Azmi AS. PAK4-NAMPT Dual Inhibition Sensitizes Pancreatic Neuroendocrine Tumors to Everolimus. Mol Cancer Ther. 2021 Oct;20(10):1836-1845. doi: 10.1158/1535-7163.MCT-20-1105. Epub 2021 Jul 12. PMID 34253597
- DERIVEDAboukameel A, Muqbil I, Senapedis W, Baloglu E, Landesman Y, Shacham S, Kauffman M, Philip PA, Mohammad RM, Azmi AS. Novel p21-Activated Kinase 4 (PAK4) Allosteric Modulators Overcome Drug Resistance and Stemness in Pancreatic Ductal Adenocarcinoma. Mol Cancer Ther. 2017 Jan;16(1):76-87. doi: 10.1158/1535-7163.MCT-16-0205. Epub 2016 Nov 15. PMID 28062705