This study is to determine the maximum tolerated dose (MTD) and the recommended Phase 2 dose (RP2D) and to investigate the safety, pharmacokinetics (PK), pharmacodynamics, and preliminary antitumor activity of NDI-101150 given as monotherapy or in combination with pembrolizumab in adult patients with advanced solid tumors.
This is a multicenter, open-label, first-in-human, Phase 1/2 study. The study will consist of 2 phases: * The Dose Escalation Phase: designed to evaluate the safety and tolerability of NDI-101150 as monotherapy (Arm 1) and in combination with pembrolizumab (Arm 2) in patients with advanced solid tumors. * The Dose Expansion Phase: designed to evaluate the safety and efficacy of NDI-101150 as monotherapy (Arm 1) and in combination with pembrolizumab (Arm 2) in disease-specific dose expansion cohorts: gastric and gastroesophageal junction \[GEJ\] cancer, non-small cell lung cancer \[NSCLC\], and renal cell carcinoma \[RCC\]. Each phase of the study will consist of 3 periods: * A Screening period of up to 28 days during which patient eligibility will be reviewed and approved by the Sponsor. * Treatment period that will extend from Cycle 1 Day 1 until progression of disease (PD), unacceptable toxicity, withdrawal of consent, start of a new systemic anticancer treatment, discontinuation of the patient by the Investigator, or termination of the study by the Sponsor. This will also include Safety Follow-up Visit 30 days \[+3 days\] after the last dose of investigational medicinal product. * Post treatment Follow-up period which will continue until lost to follow-up, withdrawal of consent, or the End of the Study (whichever comes first).
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
106
NDI-101150 capsules
Pembrolizumab IV infusion
Honor Health Research Institute
Scottsdale, Arizona, United States
Yale Cancer Center
New Haven, Connecticut, United States
Part 1: Frequency of dose-limiting toxicities (DLTs)
Time frame: Cycle 1 (28 days)
Part 2: Objective response rate (ORR)
Time frame: Up to approximately 34 months
Part 1 and Part 2: Number of patients with adverse events (AEs) and Serious adverse events (SAEs)
Time frame: From Screening (Day -28 to Day -1) until safety follow-up (>30 days after last dose) [Assessed up to 37 months]
Part 1 and Part 2: Maximum plasma concentration (Cmax) of NDI-101150
Time frame: Cycle 1 Day 1, Cycle 2 Day 1, Cycle 1 Day 2, Cycle 2 Day 2 (Monotherapy); at EOT (end-of-treatment)/ET (early termination) [Cycle length is 28 days for monotherapy and 21 days for combination therapy] (Up to 37 months)
Part 1 and Part 2: Time to maximum plasma concentration (tmax) of NDI-101150
Time frame: Cycle 1 Day 1, Cycle 2 Day 1, Cycle 1 Day 2, Cycle 2 Day 2 (Monotherapy); at EOT (end-of-treatment)/ET (early termination) [Cycle length is 28 days for monotherapy and 21 days for combination therapy] (Up to 37 months)
Part 1 and Part 2: Area under the concentration-time curve from time zero to the last observable concentration (AUC0-t) of NDI-101150
Time frame: Cycle 1 Day 1, Cycle 2 Day 1, Cycle 1 Day 2, Cycle 2 Day 2 (Monotherapy); at EOT (end-of-treatment)/ET (early termination) [Cycle length is 28 days for monotherapy and 21 days for combination therapy] (Up to 37 months)
Part 1 and Part 2: Area under the concentration-time curve extrapolated to infinity (AUC0-∞) of NDI-101150
Time frame: Cycle 1 Day 1, Cycle 2 Day 1, Cycle 1 Day 2, Cycle 2 Day 2 (Monotherapy); at EOT (end-of-treatment)/ET (early termination) [Cycle length is 28 days for monotherapy and 21 days for combination therapy] (Up to 37 months)
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Georgetown University
Washington D.C., District of Columbia, United States
Ocala Oncology Center
Ocala, Florida, United States
Norton Cancer Institute
Louisville, Kentucky, United States
University of Maryland Greenebaum Comprehensive Cancer Center
Baltimore, Maryland, United States
Henry Ford Cancer
Detroit, Michigan, United States
HealthPartners Cancer Research Center
Saint Paul, Minnesota, United States
Washington University
St Louis, Missouri, United States
Hackensack University
Hackensack, New Jersey, United States
...and 9 more locations
Part 1: Objective response rate (ORR)
Time frame: Assessed up to 37 months
Part 1 and Part 2: Progression-free survival (PFS)
Time frame: From first dose until confirmed progression of disease (PD) or death (Assessed up to 37 months)
Part 1 and Part 2: Duration of response (DOR)
Time frame: Time from first response until confirmed PD (Assessed up to 37 months)
Part 1 and Part 2: Time to response (TTR)
Time frame: Time from first dose until first response (Assessed up to 37 months)
Part 2: Overall survival
Time frame: Assessed up to 37 months