Solid TumorsPhase 1PANAMANCT02702492
PAK4 and NAMPT in Patients With Solid Malignancies or NHL (PANAMA)
A Phase 1 study testing KPT-9274, Niacin ER and Nivolumab in people with Solid Tumors and NHL, run by Karyopharm Therapeutics Inc at 8 sites in 2 countries.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Solid Tumors, NHL
- What is being tested?
- KPT-9274, Niacin ER and Nivolumab
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 8 sitesin 2 countries
- Study dates
- 8 Jun 2016to 26 Jan 2021
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Participants must meet all of the following inclusion criteria to be eligible to enroll in the Part C of this study.
- 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.
- ECOG performance status of ≤ 2.
- Life expectancy of ≥ 3 months.
- 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),
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- 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).
- 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.
- Adequate hematopoietic function:
- Total WBC count ≥ 1500/mm³, ANC ≥ 1000/mm³, Hb ≥ 10.0 g/dL, platelet count ≥ 100,000/mm³
Who cannot join
- Participants meeting any of the following exclusion criteria are not eligible to enroll in this study.
- ≤ 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.
- 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.
- 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.
- Active infection with completion of therapeutic antibiotics, antivirals, or antifungals within one week prior to C1D1. Prophylactic antibiotics, antivirals or antifungals are permitted.
- Significantly diseased or obstructed gastrointestinal tract or uncontrolled vomiting or diarrhea that could interfere with the absorption of KPT-9274.
- Active peptic ulcer disease or other active gastrointestinal bleeds.
- 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.
Trial locations and contacts
8 sites in 2 countries.
8 sites in 2 countries
United States7 sites
University of Colorado Cancer Center
Aurora, Colorado, 80045
MD Anderson Cancer Center
Houston, Texas, 77030
UCLA Health
Los Angeles, California, 90024
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, 37232
NYU-Laura & Isaac Perlmutter Cancer Center
New York, New York, 100016
Mayo Clinic Rochester
Rochester, Minnesota, 55905
Georgetown University, Lombardi Comprehensive Cancer Center
Washington D.C., District of Columbia, 20007
About this study
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 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).
Read the detailed description
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.
- Conditions
- Solid Tumors, NHL
- Being tested
- KPT-9274, Niacin ER, Nivolumab
- Keywords
- PAK4, KPT-9274, Karyopharm, NHL, Solid Tumors, NAMPT, Melanoma
- Medical subject headings
- Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
KPT-9274Drug
Niacin ERDrug
NivolumabDrug
Also called Opdivo®
| Study group | Role | What they receive |
|---|---|---|
| Part A: KPT-9274 10mg | Experimental | Participants received a 10 milligrams (mg) of oral tablets of KPT-9274 three times a week every other day during each 28 day cycle. Receives: Drug: KPT-9274 |
| Part A: KPT-9274 20mg | Experimental | Participants received a 20mg of oral tablets of KPT-9274 three times a week every other day during each 28 day cycle. Receives: Drug: KPT-9274 |
| Part A: KPT-9274 30mg | Experimental | Participants received a 30mg of oral tablets of KPT-9274 three times a week every other day during each 28 day cycle. Receives: Drug: KPT-9274 |
| Part A: KPT-9274 40mg | Experimental | Participants received a 40mg of oral tablets of KPT-9274 three times a week every other day during each 28 day cycle. Receives: Drug: KPT-9274 |
| Part A: KPT-9274 40mg BIW | Experimental | Participants received KPT-9274 40mg of oral tablet biweekly (BIW) during each 28-day cycle. Receives: Drug: KPT-9274 |
| Part B: KPT-9274 30mg + Niacin 500mg | Experimental | Participants received KPT-9274 30mg of oral tablet along with a starting dose of 500mg niacin extended release (ER) orally three times a week every other day during each 28-day cycle. Receives: Drug: KPT-9274; Drug: Niacin ER |
| Part B: KPT-9274 40mg + Niacin 500mg | Experimental | Participants received KPT-9274 40mg of oral tablet along with a starting dose of 500mg niacin ER orally three times a week every other day during each 28-day cycle. Receives: Drug: KPT-9274; Drug: Niacin ER |
| Part B: KPT-9274 60mg + Niacin 500mg | Experimental | Participants received KPT-9274 60mg of oral tablet along with a starting dose of 500mg niacin ER orally three times a week every other day during each 28-day cycle. Receives: Drug: KPT-9274; Drug: Niacin ER |
| Part B: KPT-9274 80mg + Niacin 500mg | Experimental | Participants received KPT-9274 80mg of oral tablet along with a starting dose of 500mg niacin ER orally three times a week every other day during each 28-day cycle. Receives: Drug: KPT-9274; Drug: Niacin ER |
| Part B: KPT-9274 100mg + Niacin 500mg | Experimental | Participants received KPT-9274 100mg of oral tablet along with a starting dose of 500mg niacin ER orally three times a week every other day during each 28-day cycle. Receives: Drug: KPT-9274; Drug: Niacin ER |
| Part C: KPT-9274 20mg + Nivolumab 480mg | Experimental | Participants received KPT-9274 20mg of oral tablet three times a week every other day during each 28-day cycle along with 480mg of nivolumab intravenous infusion on Day 1 of each cycle (once every 4-week cycle). Receives: Drug: KPT-9274; Drug: Nivolumab |
| Part C: KPT-9274 30mg + Nivolumab 480mg | Experimental | Participants received KPT-9274 30mg of oral tablet three times a week every other day during each 28-day cycle along with 480mg of nivolumab intravenous infusion on Day 1 of each cycle (once every 4-week cycle). Receives: Drug: KPT-9274; Drug: Nivolumab |
| Part C: KPT-9274 40mg + Nivolumab 480mg | Experimental | Participants received KPT-9274 40mg of oral tablet three times a week every other day during each 28-day cycle along with 480mg of nivolumab intravenous infusion on Day 1 of each cycle (once every 4-week cycle). Receives: Drug: KPT-9274; Drug: Nivolumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Tolerated Dose (MTD) for KPT-9274
The MTD was defined as the highest dose at which less than or equal to (<=) 1 participant experienced a dose limiting toxicity (DLT) in Cycle 1. A DLT was defined as an adverse event (AE) or abnormal laboratory value occurring within the first 28 days of treatment of KPT-9274, excluding those clearly caused by underlying disease, disease progression, or external factors.
Measured: From start of study drug administration up to 44 weeks
Number of Dose Limiting Toxicities (DLT) Experienced by Participants
A DLT was defined as an AE or abnormal laboratory value occurring within the first 28 days of KPT-9274 treatment, excluding those clearly caused by underlying disease, disease progression, or extraneous causes, and meets any of the criteria for defining dose limiting toxicities.
Measured: At Cycle 1 only (28-day cycle)
Number of Participants With Adverse Event (AE) of Severity Grade >= 3 or 4, Serious AEs, and AEs Leading to Treatment Discontinuation
The AE severity was graded on a scale from 1 to 4 using the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.03; any events not specifically listed in the scale were defined as: Grade 1 is mild; Grade 2 is moderate; Grade 3 is severe or medically significant; Grade 4 is life-threatening. An SAE was any untoward medical occurrence that at any dose met one, more of the following criteria: results in death, life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent, significant disability/incapacity, a congenital abnormality/birth defect, an important medical event. The AE leading to treatment discontinuation in the study.
Measured: From start of study drug administration up to 49 weeks
Percentage of Participants With Overall Response Rate (ORR)
The ORR was defined as percentage of participants who had a response of partial response (PR) or complete response (CR). The PR was achieved when a participant had at least a 30 percent (%) decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. The CR was achieved in a participant when all target lesions disappeared. Any pathological lymph nodes (whether target or non target) must have reduction in the short axis to <10 millimeter (mm).
Measured: From date of randomization up to 44 weeks
Percentage of Participants With Disease Control Rate (DCR)
The DCR was defined as percentage of participants who have a response of CR, PR, and stable disease (SD) >= 16 weeks, DCR = CR + PR+ SD. The PR was achieved when a participant had at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. The CR was achieved in a participant when all target lesions disappeared. Any pathological lymph nodes (whether target or non-target) must have reduction in the short axis to <10mm. The SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD).
Measured: From date of the first study treatment up to 44 weeks
Progression-free Survival (PFS)
The PFS was defined as the duration of time from date of the first study treatment until the first date that PD is objectively documented or death due to any cause. The PD is defined as at least a 20% increase in the sum of diameters of measured lesions taking as references the smallest sum of diameters recorded since the treatment started. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5mm. Appearance of one or more new lesions will also constitute PD.
Measured: From the date of first study treatment until the first date of PD, or death due (up to 44 weeks)
Overall Survival (OS)
The OS was defined as the duration of time from date of the first study treatment until death from any cause.
Measured: From date of the first study treatment until death (up to 44 weeks)
Time to Progression (TTP)
The TTP was defined as the duration of time from date of the first study treatment until the first date that PD was objectively documented or death due to PD.
Measured: From date of the first study treatment until the first date of PD or death (up to 44 weeks)
Duration of Response (DOR)
The DOR was defined as the duration of time from the first meeting CR or PR measurement criteria (whichever occurs first) until the first date diseases progression.
Measured: Up to 44 weeks
Secondary outcomes (5)
Maximum Plasma Concentration (Cmax) in Participants Who Received KPT-9274
Cmax achieved by the KPT-9274 after the first dose administrations.
Measured: Cycle 1 and 2: Pre-dose, 3, 6, 8, 24, and 48 hours post-dose (each cycle =28 days)
Time-to-peak Plasma Concentration (Tmax) in Participants Who Received KPT-9274
Time taken by KPT-9274 to achieve maximum plasma concentration after the first dose administration.
Measured: Cycle 1 and 2: Pre-dose, 3, 6, 8, 24, and 48 hours post-dose (each cycle =28 days)
Terminal Half-life (T1/2) in Participants Who Received KPT-9274
The T1/2 was defied as the time it takes for the concentration of KPT-9274 in the plasma to be reduced by 50%.
Measured: Cycle 1 and 2: Pre-dose, 3, 6, 8, 24, and 48 hours post-dose (each cycle =28 days)
Volume of Distribution (Vd/F) in Participants Who Received KPT-9274
The Vd/F was defined as MRT*CL/F, where MRT is the mean residence time (calculated as AUMC[0-tau]/AUC[0-tau], where AUMC[0-tau] is the area under the first moment curve determined as the area under the concentration*time versus time curve).
Measured: Cycle 1 and 2: Pre-dose, 3, 6, 8, 24, and 48 hours post-dose (each cycle =28 days)
Apparent Plasma Clearance (CL/F) in Participants Who Received KPT-9274
The CL/F was calculated as the KPT-9274 dose administered divided by the area-under-the-curve of KPT-9274 plasma concentration versus (vs) time.
Measured: Cycle 1 and 2: Pre-dose, 3, 6, 8, 24, and 48 hours post-dose (each cycle =28 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Mar 2016 (estimated)
- Study start8 Jun 2016
- Primary completion26 Jan 2021
- Study completion26 Jan 2021
Why it stopped: sponsor decision
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Solid TumorsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- Karyopharm Therapeutics Inc
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02702492
- Sponsor's protocol ID
- KCP-9274-901
- Acronym
- PANAMA
- Status last verified
- Oct 2024
- First submitted
- 3 Mar 2016
- Last updated
- 25 Nov 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Razak 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.
PubMed 41824279Han 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.
PubMed 37864885Mpilla 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.
PubMed 34253597Aboukameel 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.
PubMed 28062705
Study at a glance
From the registry record, last updated by the sponsor on 25 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02702492
- Acronym / sponsor ID
- PANAMA / KCP-9274-901
- Conditions
- Solid Tumors, NHL
- Keywords
- PAK4, KPT-9274, Karyopharm, NHL, Solid Tumors, NAMPT, Melanoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: sponsor decision
- Enrolment
- 60 participants (actual)
- Lead sponsor
- Karyopharm Therapeutics IncIndustry (pharma, biotech, devices)
- Study start
- 8 Jun 2016 (actual)
- Primary completion
- 26 Jan 2021 (actual)
- Study completion
- 26 Jan 2021 (actual)
- First posted
- 8 Mar 2016 (estimated)
- Results
- Posted 25 Nov 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 13
| Arm | Type | Receives |
|---|---|---|
| Part A: KPT-9274 10mg | Experimental | Drug: KPT-9274Participants received a 10 milligrams (mg) of oral tablets of KPT-9274 three times a week every other day during each 28 day cycle. |
| Part A: KPT-9274 20mg | Experimental | Drug: KPT-9274Participants received a 20mg of oral tablets of KPT-9274 three times a week every other day during each 28 day cycle. |
| Part A: KPT-9274 30mg | Experimental | Drug: KPT-9274Participants received a 30mg of oral tablets of KPT-9274 three times a week every other day during each 28 day cycle. |
| Part A: KPT-9274 40mg | Experimental | Drug: KPT-9274Participants received a 40mg of oral tablets of KPT-9274 three times a week every other day during each 28 day cycle. |
| Part A: KPT-9274 40mg BIW | Experimental | Drug: KPT-9274Participants received KPT-9274 40mg of oral tablet biweekly (BIW) during each 28-day cycle. |
| Part B: KPT-9274 30mg + Niacin 500mg | Experimental | Drug: KPT-9274, Drug: Niacin ERParticipants received KPT-9274 30mg of oral tablet along with a starting dose of 500mg niacin extended release (ER) orally three times a week every other day during each 28-day cycle. |
| Part B: KPT-9274 40mg + Niacin 500mg | Experimental | Drug: KPT-9274, Drug: Niacin ERParticipants received KPT-9274 40mg of oral tablet along with a starting dose of 500mg niacin ER orally three times a week every other day during each 28-day cycle. |
| Part B: KPT-9274 60mg + Niacin 500mg | Experimental | Drug: KPT-9274, Drug: Niacin ERParticipants received KPT-9274 60mg of oral tablet along with a starting dose of 500mg niacin ER orally three times a week every other day during each 28-day cycle. |
| Part B: KPT-9274 80mg + Niacin 500mg | Experimental | Drug: KPT-9274, Drug: Niacin ERParticipants received KPT-9274 80mg of oral tablet along with a starting dose of 500mg niacin ER orally three times a week every other day during each 28-day cycle. |
| Part B: KPT-9274 100mg + Niacin 500mg | Experimental | Drug: KPT-9274, Drug: Niacin ERParticipants received KPT-9274 100mg of oral tablet along with a starting dose of 500mg niacin ER orally three times a week every other day during each 28-day cycle. |
| Part C: KPT-9274 20mg + Nivolumab 480mg | Experimental | Drug: KPT-9274, Drug: NivolumabParticipants received KPT-9274 20mg of oral tablet three times a week every other day during each 28-day cycle along with 480mg of nivolumab intravenous infusion on Day 1 of each cycle (once every 4-week cycle). |
| Part C: KPT-9274 30mg + Nivolumab 480mg | Experimental | Drug: KPT-9274, Drug: NivolumabParticipants received KPT-9274 30mg of oral tablet three times a week every other day during each 28-day cycle along with 480mg of nivolumab intravenous infusion on Day 1 of each cycle (once every 4-week cycle). |
| Part C: KPT-9274 40mg + Nivolumab 480mg | Experimental | Drug: KPT-9274, Drug: NivolumabParticipants received KPT-9274 40mg of oral tablet three times a week every other day during each 28-day cycle along with 480mg of nivolumab intravenous infusion on Day 1 of each cycle (once every 4-week cycle). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Participants must meet all of the following inclusion criteria to be eligible to enroll in the Part C of this study.
- 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.
- ECOG performance status of ≤ 2.
- Life expectancy of ≥ 3 months.
- Adequate hepatic function:
Key exclusion criteria (8 listed)
- Participants meeting any of the following exclusion criteria are not eligible to enroll in this study.
- ≤ 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.
- 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.
- 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.
- Active infection with completion of therapeutic antibiotics, antivirals, or antifungals within one week prior to C1D1. Prophylactic antibiotics, antivirals or antifungals are permitted.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| KPT-9274 | Drug | Part A: KPT-9274 10mg, Part A: KPT-9274 20mg, Part A: KPT-9274 30mg, Part A: KPT-9274 40mg, Part A: KPT-9274 40mg BIW, Part B: KPT-9274 100mg + Niacin 500mg, Part B: KPT-9274 30mg + Niacin 500mg, Part B: KPT-9274 40mg + Niacin 500mg, Part B: KPT-9274 60mg + Niacin 500mg, Part B: KPT-9274 80mg + Niacin 500mg, Part C: KPT-9274 20mg + Nivolumab 480mg, Part C: KPT-9274 30mg + Nivolumab 480mg, Part C: KPT-9274 40mg + Nivolumab 480mg |
| Niacin ER | Drug | Part B: KPT-9274 100mg + Niacin 500mg, Part B: KPT-9274 30mg + Niacin 500mg, Part B: KPT-9274 40mg + Niacin 500mg, Part B: KPT-9274 60mg + Niacin 500mg, Part B: KPT-9274 80mg + Niacin 500mg |
| NivolumabAlso: Opdivo® | Drug | Part C: KPT-9274 20mg + Nivolumab 480mg, Part C: KPT-9274 30mg + Nivolumab 480mg, Part C: KPT-9274 40mg + Nivolumab 480mg |
Primary outcome
Maximum Tolerated Dose (MTD) for KPT-9274
Time frame: From start of study drug administration up to 44 weeks
The MTD was defined as the highest dose at which less than or equal to (<=) 1 participant experienced a dose limiting toxicity (DLT) in Cycle 1. A DLT was defined as an adverse event (AE) or abnormal laboratory value occurring within the first 28 days of treatment of KPT-9274, excluding those clearly caused by underlying disease, disease progression, or external factors.
Number of Dose Limiting Toxicities (DLT) Experienced by Participants
Time frame: At Cycle 1 only (28-day cycle)
A DLT was defined as an AE or abnormal laboratory value occurring within the first 28 days of KPT-9274 treatment, excluding those clearly caused by underlying disease, disease progression, or extraneous causes, and meets any of the criteria for defining dose limiting toxicities.
Number of Participants With Adverse Event (AE) of Severity Grade >= 3 or 4, Serious AEs, and AEs Leading to Treatment Discontinuation
Time frame: From start of study drug administration up to 49 weeks
The AE severity was graded on a scale from 1 to 4 using the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.03; any events not specifically listed in the scale were defined as: Grade 1 is mild; Grade 2 is moderate; Grade 3 is severe or medically significant; Grade 4 is life-threatening. An SAE was any untoward medical occurrence that at any dose met one, more of the following criteria: results in death, life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent, significant disability/incapacity, a congenital abnormality/birth defect, an important medical event. The AE leading to treatment discontinuation in the study.
Percentage of Participants With Overall Response Rate (ORR)
Time frame: From date of randomization up to 44 weeks
The ORR was defined as percentage of participants who had a response of partial response (PR) or complete response (CR). The PR was achieved when a participant had at least a 30 percent (%) decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. The CR was achieved in a participant when all target lesions disappeared. Any pathological lymph nodes (whether target or non target) must have reduction in the short axis to <10 millimeter (mm).
Percentage of Participants With Disease Control Rate (DCR)
Time frame: From date of the first study treatment up to 44 weeks
The DCR was defined as percentage of participants who have a response of CR, PR, and stable disease (SD) >= 16 weeks, DCR = CR + PR+ SD. The PR was achieved when a participant had at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. The CR was achieved in a participant when all target lesions disappeared. Any pathological lymph nodes (whether target or non-target) must have reduction in the short axis to <10mm. The SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD).
Progression-free Survival (PFS)
Time frame: From the date of first study treatment until the first date of PD, or death due (up to 44 weeks)
The PFS was defined as the duration of time from date of the first study treatment until the first date that PD is objectively documented or death due to any cause. The PD is defined as at least a 20% increase in the sum of diameters of measured lesions taking as references the smallest sum of diameters recorded since the treatment started. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5mm. Appearance of one or more new lesions will also constitute PD.
Overall Survival (OS)
Time frame: From date of the first study treatment until death (up to 44 weeks)
The OS was defined as the duration of time from date of the first study treatment until death from any cause.
Time to Progression (TTP)
Time frame: From date of the first study treatment until the first date of PD or death (up to 44 weeks)
The TTP was defined as the duration of time from date of the first study treatment until the first date that PD was objectively documented or death due to PD.
Duration of Response (DOR)
Time frame: Up to 44 weeks
The DOR was defined as the duration of time from the first meeting CR or PR measurement criteria (whichever occurs first) until the first date diseases progression.
5 secondary outcomes
Maximum Plasma Concentration (Cmax) in Participants Who Received KPT-9274
Time frame: Cycle 1 and 2: Pre-dose, 3, 6, 8, 24, and 48 hours post-dose (each cycle =28 days)
Time-to-peak Plasma Concentration (Tmax) in Participants Who Received KPT-9274
Time frame: Cycle 1 and 2: Pre-dose, 3, 6, 8, 24, and 48 hours post-dose (each cycle =28 days)
Terminal Half-life (T1/2) in Participants Who Received KPT-9274
Time frame: Cycle 1 and 2: Pre-dose, 3, 6, 8, 24, and 48 hours post-dose (each cycle =28 days)
Volume of Distribution (Vd/F) in Participants Who Received KPT-9274
Time frame: Cycle 1 and 2: Pre-dose, 3, 6, 8, 24, and 48 hours post-dose (each cycle =28 days)
Apparent Plasma Clearance (CL/F) in Participants Who Received KPT-9274
Time frame: Cycle 1 and 2: Pre-dose, 3, 6, 8, 24, and 48 hours post-dose (each cycle =28 days)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Nov 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 41824279Razak 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.
- Derived from this study: PubMed 37864885Han 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.
- Derived from this study: PubMed 34253597Mpilla 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.
- Derived from this study: PubMed 28062705Aboukameel 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.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
8 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing KPT-9274, Niacin ER and Nivolumab in people with Solid Tumors and NHL, run by Karyopharm Therapeutics Inc at 8 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 25 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 25 Nov 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum Tolerated Dose (MTD) for KPT-9274 (time frame: From start of study drug administration up to 44 weeks). The study lists 9 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02702492, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Nov 2024.