PAK4 and NAMPT in Patients With Solid Malignancies or NHL (PANAMA)

Brief summary public domain (ClinicalTrials.gov)

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).

Detailed description public domain (ClinicalTrials.gov)

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.

Posted results (ClinicalTrials.gov registry) · primary outcome public domain (ClinicalTrials.gov)

Maximum Tolerated Dose (MTD) for KPT-9274 [From start of study drug administration up to 44 weeks]. Count Of Participants, Participants. Part A: KPT-9274 10mg (n=3): NA [MTD was not determined based on insufficient number of participants with events.]; Part A: KPT-9274 20mg (n=3): NA [MTD was not determined based on insufficient number of participants with events.]; Part A: KPT-9274 30mg (n=5): NA [MTD was not determined based on insufficient number of participants with events.]; Part A: KPT-9274 40mg (n=7): NA [MTD was not determined based on insufficient number of participants with events.]; Part A: KPT-9274 40mg BIW (n=5): NA [MTD was not determined based on insufficient number of participants with events.]; Part B: KPT-9274 30mg + Niacin 500mg (n=3): NA [MTD was not determined based on insufficient number of participants with events.]; Part B: KPT-9274 40mg + Niacin 500mg (n=4): NA [MTD was not determined based on insufficient number of participants with events.]; Part B: KPT-9274 60mg + Niacin 500mg (n=12): NA [MTD was not determined based on insufficient number of participants with events.]; Part B: KPT-9274 80mg + Niacin 500mg (n=7): NA [MTD was not determined based on insufficient number of participants with events.]; Part B: KPT-9274 100mg + Niacin 500mg (n=1): NA [MTD was not determined based on insufficient number of participants with events.]; Part C: KPT-9274 20mg + Nivolumab 480mg (n=1): NA [MTD was not determined based on insufficient number of participants with events.]; Part C: KPT-9274 30mg + Nivolumab 480mg (n=5): NA [MTD was not determined based on insufficient number of participants with events.]; Part C: KPT-9274 40mg + Nivolumab 480mg (n=4): NA [MTD was not determined based on insufficient number of participants with events.].

Posted results (ClinicalTrials.gov registry) · primary outcome public domain (ClinicalTrials.gov)

Number of Dose Limiting Toxicities (DLT) Experienced by Participants [At Cycle 1 only (28-day cycle)]. Number, Number of DLTs. Part A: KPT-9274 10mg (n=3): 0; Part A: KPT-9274 20mg (n=3): 0; Part A: KPT-9274 30mg (n=5): 0; Part A: KPT-9274 40mg (n=7): 1; Part A: KPT-9274 40mg BIW (n=5): 0; Part B: KPT-9274 30mg + Niacin 500mg (n=3): 0; Part B: KPT-9274 40mg + Niacin 500mg (n=4): 0; Part B: KPT-9274 60mg + Niacin 500mg (n=12): 0; Part B: KPT-9274 80mg + Niacin 500mg (n=7): 2; Part B: KPT-9274 100mg + Niacin 500mg (n=1): 0; Part C: KPT-9274 20mg + Nivolumab 480mg (n=1): 0; Part C: KPT-9274 30mg + Nivolumab 480mg (n=5): 0; Part C: KPT-9274 40mg + Nivolumab 480mg (n=4): 0.

Posted results (ClinicalTrials.gov registry) · primary outcome public domain (ClinicalTrials.gov)

Number of Participants With Adverse Event (AE) of Severity Grade >= 3 or 4, Serious AEs, and AEs Leading to Treatment Discontinuation [From start of study drug administration up to 49 weeks]. Count Of Participants, Participants. Maximum Grade 3/4 AEs: Part A: KPT-9274 10mg (n=3): 1; Part A: KPT-9274 20mg (n=3): 2; Part A: KPT-9274 30mg (n=5): 5; Part A: KPT-9274 40mg (n=7): 7; Part A: KPT-9274 40mg BIW (n=5): 3; Part B: KPT-9274 30mg + Niacin 500mg (n=3): 2; Part B: KPT-9274 40mg + Niacin 500mg (n=4): 3; Part B: KPT-9274 60mg + Niacin 500mg (n=12): 10; Part B: KPT-9274 80mg + Niacin 500mg (n=7): 7; Part B: KPT-9274 100mg + Niacin 500mg (n=1): 1; Part C: KPT-9274 20mg + Nivolumab 480mg (n=1): 1; Part C: KPT-9274 30mg + Nivolumab 480mg (n=5): 4; Part C: KPT-9274 40mg + Nivolumab 480mg (n=4): 3. Maximum Grade 4 AEs: Part A: KPT-9274 10mg (n=3): 0; Part A: KPT-9274 20mg (n=3): 0; Part A: KPT-9274 30mg (n=5): 1; Part A: KPT-9274 40mg (n=7): 3; Part A: KPT-9274 40mg BIW (n=5): 0; Part B: KPT-9274 30mg + Niacin 500mg (n=3): 1; Part B: KPT-9274 40mg + Niacin 500mg (n=4): 0; Part B: KPT-9274 60mg + Niacin 500mg (n=12): 0; Part B: KPT-9274 80mg + Niacin 500mg (n=7): 0; Part B: KPT-9274 100mg + Niacin 500mg (n=1): 1; Part C: KPT-9274 20mg + Nivolumab 480mg (n=1): 0; Part C: KPT-9274 30mg + Nivolumab 480mg (n=5): 0; Part C: KPT-9274 40mg + Nivolumab 480mg (n=4): 1. Serious AEs: Part A: KPT-9274 10mg (n=3): 0; Part A: KPT-9274 20mg (n=3): 2; Part A: KPT-9274 30mg (n=5): 2; Part A: KPT-9274 40mg (n=7): 3; Part A: KPT-9274 40mg BIW (n=5): 0; Part B: KPT-9274 30mg + Niacin 500mg (n=3): 1; Part B: KPT-9274 40mg + Niacin 500mg (n=4): 1; Part B: KPT-9274 60mg + Niacin 500mg (n=12): 6; Part B: KPT-9274 80mg + Niacin 500mg (n=7): 1; Part B: KPT-9274 100mg + Niacin 500mg (n=1): 1; Part C: KPT-9274 20mg + Nivolumab 480mg (n=1): 1; Part C: KPT-9274 30mg + Nivolumab 480mg (n=5): 2; Part C: KPT-9274 40mg + Nivolumab 480mg (n=4): 2. AEs Leading to Study Treatment Discontinuation: Part A: KPT-9274 10mg (n=3): 0; Part A: KPT-9274 20mg (n=3): 0; Part A: KPT-9274 30mg (n=5): 1; Part A: KPT-9274 40mg (n=7): 2; Part A: KPT-9274 40mg BIW (n=5): 1; Part B: KPT-9274 30mg + Niacin 500mg (n=3): 0; Part B: KPT-9274 40mg + Niacin 500mg (n=4): 1; Part B: KPT-9274 60mg + Niacin 500mg (n=12): 0; Part B: KPT-9274 80mg + Niacin 500mg (n=7): 2; Part B: KPT-9274 100mg + Niacin 500mg (n=1): 0; Part C: KPT-9274 20mg + Nivolumab 480mg (n=1): 0; Part C: KPT-9274 30mg + Nivolumab 480mg (n=5): 0; Part C: KPT-9274 40mg + Nivolumab 480mg (n=4): 1.

Posted results (ClinicalTrials.gov registry) · primary outcome public domain (ClinicalTrials.gov)

Percentage of Participants With Overall Response Rate (ORR) [From date of randomization up to 44 weeks].

Posted results (ClinicalTrials.gov registry) · primary outcome public domain (ClinicalTrials.gov)

Percentage of Participants With Disease Control Rate (DCR) [From date of the first study treatment up to 44 weeks].

Posted results (ClinicalTrials.gov registry) · primary outcome public domain (ClinicalTrials.gov)

Progression-free Survival (PFS) [From the date of first study treatment until the first date of PD, or death due (up to 44 weeks)].

Posted results (ClinicalTrials.gov registry) · primary outcome public domain (ClinicalTrials.gov)

Overall Survival (OS) [From date of the first study treatment until death (up to 44 weeks)].

Posted results (ClinicalTrials.gov registry) · primary outcome public domain (ClinicalTrials.gov)

Time to Progression (TTP) [From date of the first study treatment until the first date of PD or death (up to 44 weeks)].

Posted results (ClinicalTrials.gov registry) · primary outcome public domain (ClinicalTrials.gov)

Duration of Response (DOR) [Up to 44 weeks].

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Maximum Plasma Concentration (Cmax) in Participants Who Received KPT-9274 [Cycle 1 and 2: Pre-dose, 3, 6, 8, 24, and 48 hours post-dose (each cycle =28 days)].

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Time-to-peak Plasma Concentration (Tmax) in Participants Who Received KPT-9274 [Cycle 1 and 2: Pre-dose, 3, 6, 8, 24, and 48 hours post-dose (each cycle =28 days)].

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Terminal Half-life (T1/2) in Participants Who Received KPT-9274 [Cycle 1 and 2: Pre-dose, 3, 6, 8, 24, and 48 hours post-dose (each cycle =28 days)].

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Volume of Distribution (Vd/F) in Participants Who Received KPT-9274 [Cycle 1 and 2: Pre-dose, 3, 6, 8, 24, and 48 hours post-dose (each cycle =28 days)].

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Apparent Plasma Clearance (CL/F) in Participants Who Received KPT-9274 [Cycle 1 and 2: Pre-dose, 3, 6, 8, 24, and 48 hours post-dose (each cycle =28 days)].