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

Solid Tumor Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05128487
• Other study ID #: 1150-101
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: November 5, 2021
• Est. completion date: December 2024

Study information

• Verified date: May 2024
• Source: Nimbus Therapeutics
• Contact: Study Coordinator
• Phone: 8579992009
• Email: clinical[@]nimbustx.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 106
• Est. completion date: December 2024
• Est. primary completion date: September 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Neoplasms
• Solid Tumor

Intervention

Drug:
• NDI-101150
NDI-101150 capsules
• Pembrolizumab
Pembrolizumab IV infusion

Locations

Country	Name	City	State
United States	University of Maryland Greenebaum Comprehensive Cancer Center	Baltimore	Maryland
United States	Gabrail Cancer Center	Canton	Ohio
United States	Texas Oncology - Baylor Charles A. Sammons Cancer Center	Dallas	Texas
United States	Henry Ford Cancer	Detroit	Michigan
United States	NEXT Oncology	Fairfax	Virginia
United States	Hackensack University	Hackensack	New Jersey
United States	Center for Oncology and Blood Disorders	Houston	Texas
United States	Oncology Consultants	Houston	Texas
United States	Norton Cancer Institute	Louisville	Kentucky
United States	University of Wisconsin	Madison	Wisconsin
United States	Columbia University Irving Medical Center	New York	New York
United States	Ocala Oncology Center	Ocala	Florida
United States	Stephenson Cancer Center	Oklahoma City	Oklahoma
United States	Washington University	Saint Louis	Missouri
United States	HealthPartners Cancer Research Center	Saint Paul	Minnesota
United States	NEXT Oncology	San Antonio	Texas
United States	Honor Health Research Institute	Scottsdale	Arizona
United States	Northwest Medical Specialties	Tacoma	Washington
United States	Georgetown University	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Nimbus Saturn, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Part 1: Frequency of dose-limiting toxicities (DLTs)		Cycle 1 (28 days)
Primary	Part 2: Objective response rate (ORR)		Up to approximately 34 months
Secondary	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]
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	Part 1 and Part 2: Area under the concentration-time curve extrapolated to infinity (AUC0-8) 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)
Secondary	Part 1: Objective response rate (ORR)		Assessed up to 37 months
Secondary	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)
Secondary	Part 1 and Part 2: Duration of response (DOR)		Time from first response until confirmed PD (Assessed up to 37 months)
Secondary	Part 1 and Part 2: Time to response (TTR)		Time from first dose until first response (Assessed up to 37 months)
Secondary	Part 2: Overall survival		Assessed up to 37 months