Clinical trial NCT05128487: A Study of NDI 1150-101 in Patients With Solid Tumors
Official title: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Solid Tumor
Renal Cell Carcinoma (Kidney Cancer)
Gastric and Gastroesophageal Junction (GEJ) Adenocarcinoma
Non-Small Cell Lung Cancer
Keywords: Dose escalation phase
Dose expansion phase
Hematopoietic progenitor kinase 1
NDI-101150
First-in-human
Maximum tolerated dose
Recommended Phase 2 dose
Renal Cell Carcinoma
Gastric and gastroesophageal junction cancer
Non-Small Cell Lung Cancer
Lead sponsor: Nimbus Therapeutics
Sponsor class: INDUSTRY
First posted: 2021-11-22
Enrollment: 106
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: 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: 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).

Eligibility criteria: 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.

Primary outcomes:
measure: Part 1: Frequency of dose-limiting toxicities (DLTs)
timeFrame: Cycle 1 (28 days)
measure: Part 2: Objective response rate (ORR)
timeFrame: Up to approximately 34 months
Secondary outcomes:
measure: Part 1 and Part 2: Number of patients with adverse events (AEs) and Serious adverse events (SAEs)
timeFrame: From Screening (Day -28 to Day -1) until safety follow-up (>30 days after last dose) [Assessed up to 37 months]
measure: Part 1 and Part 2: Maximum plasma concentration (Cmax) of NDI-101150
timeFrame: 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)
measure: Part 1 and Part 2: Time to maximum plasma concentration (tmax) of NDI-101150
timeFrame: 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)
measure: Part 1 and Part 2: Area under the concentration-time curve from time zero to the last observable concentration (AUC0-t) of NDI-101150
timeFrame: 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)
measure: Part 1 and Part 2: Area under the concentration-time curve extrapolated to infinity (AUC0-∞) of NDI-101150
timeFrame: 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)
measure: Part 1: Objective response rate (ORR)
timeFrame: Assessed up to 37 months
measure: Part 1 and Part 2: Progression-free survival (PFS)
timeFrame: From first dose until confirmed progression of disease (PD) or death (Assessed up to 37 months)
measure: Part 1 and Part 2: Duration of response (DOR)
timeFrame: Time from first response until confirmed PD (Assessed up to 37 months)
measure: Part 1 and Part 2: Time to response (TTR)
timeFrame: Time from first dose until first response (Assessed up to 37 months)
measure: Part 2: Overall survival
timeFrame: Assessed up to 37 months
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Honor Health Research Institute
state: Arizona
city: New Haven
country: United States
facility: Yale Cancer Center
state: Connecticut
city: Washington
country: United States
facility: Georgetown University
state: District of Columbia
city: Ocala
country: United States
facility: Ocala Oncology Center
state: Florida
city: Louisville
country: United States
facility: Norton Cancer Institute
state: Kentucky
city: Baltimore
country: United States
facility: University of Maryland Greenebaum Comprehensive Cancer Center
state: Maryland
city: Detroit
country: United States
facility: Henry Ford Cancer
state: Michigan
city: Saint Paul
country: United States
facility: HealthPartners Cancer Research Center
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: Hackensack
country: United States
facility: Hackensack University
state: New Jersey
city: New York
country: United States
facility: Columbia University Irving Medical Center
state: New York
city: Oklahoma City
country: United States
facility: Stephenson Cancer Center
state: Oklahoma
city: Dallas
country: United States
facility: Texas Oncology - Baylor Charles A. Sammons Cancer Center
state: Texas
city: Houston
country: United States
facility: Center for Oncology and Blood Disorders
state: Texas
city: Houston
country: United States
facility: Oncology Consultants
state: Texas
city: San Antonio
country: United States
facility: NEXT Oncology
state: Texas
city: Fairfax
country: United States
facility: NEXT Oncology
state: Virginia
city: Tacoma
country: United States
facility: Northwest Medical Specialties
state: Washington
city: Madison
country: United States
facility: University of Wisconsin
state: Wisconsin
Study officials:
affiliation: Nimbus Saturn
name: Anita Scheuber, MD
role: STUDY_DIRECTOR
References: