A Study of NDI 1150-101 in Patients With Solid Tumors

Study Overview
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Brief Summary
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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.

Detailed Description
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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).

Official Title
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A Phase 1/2, Open-label Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Preliminary Antitumor Activity of NDI-101150 Administered as Monotherapy or in Combination With Pembrolizumab in Patients With Solid Tumors

Conditions
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Solid Tumor

Intervention / Treatment
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* Drug: NDI-101150
* Drug: Pembrolizumab


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Life expectancy of ≥ 12 weeks Measurable or non-measurable disease for Dose Escalation; measurable disease using RECIST v1.1 is required for Dose Expansion Recovered from prior therapy to Grade ≤ 1 or return to baseline status (except for alopecia) Eastern Cooperative Oncology Group (ECOG) performance status 0-1 Patients with adequate bone marrow, kidney and liver function Last dose of previous anticancer therapy ≥ 4 weeks prior to first dose of NDI-101150; includes prior anti-PD-1 or anti-PD-L1 therapy, other anticancer therapy, radiotherapy, or surgical intervention For Dose Escalation Phase Only (Dose Escalation, Monotherapy and Combination Therapy): Histologically or cytologically confirmed advanced or metastatic solid tumors for whom no standard therapies are available or refractory to standard therapy For Dose Expansion Phase (Dose Expansion, Monotherapy and Combination Therapy): Willing to consent to required tumor biopsy(ies). Histologically or cytologically confirmed advanced or metastatic G/GEJ, NSCLC or RCC for which no standard therapy is available or are refractory to standard therapy Key Exclusion Criteria: Previous solid organ or hematopoietic cell transplant Central nervous system (CNS) malignant disease not previously treated, active leptomeningeal disease, uncontrolled symptomatic CNS involvement, or CNS malignant disease requiring steroid or other therapeutic intervention Prior anticancer therapy within 2-6 weeks of trial start (depending on nature of therapy). Clinically significant cardiovascular disease History of severe hypersensitivity reaction to treatment with monoclonal antibody(ies) (for combination therapy cohorts only) History of interstitial lung disease, idiopathic pulmonary fibrosis, pneumonitis (including drug induced), organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia, etc.), or evidence of history of pneumonitis on chest computed tomography scan in the last 6 months Known additional malignancy that is active and/or in progression requiring treatment Unstable or severe uncontrolled medical condition (e.g., unstable cardiac function, unstable pulmonary condition, uncontrolled diabetes, thromboembolic event within the past 3 months) or any important medical or psychiatric illness or abnormal laboratory finding Unable to discontinue medications that are strong inducers or inhibitors of CYP3A4 and/or CYP2C8 History of severe irAE that led to permanent discontinuation of prior immunotherapy History of recent Grade >/= 3 irAE or any Grade 4 life-threatening irAE, neurologic or ocular AE of any grade while receiving prior immunotherapy NOTE: Other protocol defined Inclusion and Exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NDI-101150 (Monotherapy)<br>Patients in escalation and expansion, will receive NDI-101150 capsules orally once daily continuously in 4-week cycles (28 days). | Drug: NDI-101150<br>* NDI-101150 capsules<br>|
| Experimental: NDI-101150-Pembrolizumab (Combination therapy)<br>Patients in escalation and expansion phase, will receive NDI-101150 capsules orally once daily continuously in 3-week cycles (21 days), along with pembrolizumab via intravenous (IV) infusion at a dose of 200 mg every 3 weeks. | Drug: NDI-101150<br>* NDI-101150 capsules<br>Drug: Pembrolizumab<br>* Pembrolizumab IV infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 1: Frequency of dose-limiting toxicities (DLTs) |  | Cycle 1 (28 days) | 
| Part 2: Objective response rate (ORR) |  | Up to approximately 34 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 1 and Part 2: Number of patients with adverse events (AEs) and Serious adverse events (SAEs) |  | 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 |  | 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 |  | 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 |  | 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 |  | 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: Objective response rate (ORR) |  | Assessed up to 37 months | 
| Part 1 and Part 2: Progression-free survival (PFS) |  | 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 from first response until confirmed PD (Assessed up to 37 months) | 
| Part 1 and Part 2: Time to response (TTR) |  | Time from first dose until first response (Assessed up to 37 months) | 
| Part 2: Overall survival |  | Assessed up to 37 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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NDI-101150, Dose escalation phase, Dose expansion phase, Hematopoietic progenitor kinase 1, First-in-human, Maximum tolerated dose, Recommended Phase 2 dose, Renal Cell Carcinoma, Gastric and gastroesophageal junction cancer, Non-Small Cell Lung Cancer