Study of NGM707 as Monotherapy and in Combination With Pembrolizumab in Advanced or Metastatic Solid Tumor Malignancies

Sponsor

NGM Biopharmaceuticals, Inc (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04913337

Collaborator

Merck Sharp & Dohme LLC (Industry)

179

Enrollment

Locations

Arms

48.7

Anticipated Duration (Months)

12.8

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Study of NGM707 as Monotherapy and in Combination with Pembrolizumab in Advanced or Metastatic Solid Tumor Malignancies

Condition or Disease	Intervention/Treatment	Phase
Mesothelioma Glioblastoma Renal Cell Carcinoma Non Small Cell Lung Cancer Melanoma Pancreatic Ductal Adenocarcinoma Gastric Cancer Squamous Cell Carcinoma of Head and Neck Cholangiocarcinoma Breast Cancer Ovarian Cancer Cervical Cancer Endocervical Cancer Colorectal Cancer Esophageal Cancer	Drug: NGM707 Drug: NGM707 plus pembrolizumab Drug: NGM707 Drug: NGM707 Drug: NGM707 Drug: NGM707 plus pembrolizumab Drug: NGM707 plus pembrolizumab	Phase 1/Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

179 participants

Allocation:

Non-Randomized

Intervention Model:

Factorial Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase 1/2 Dose Escalation/Expansion Study of NGM707 as Monotherapy and in Combination With Pembrolizumab in Advanced or Metastatic Solid Tumor Malignancies

Actual Study Start Date :

Jun 9, 2021

Anticipated Primary Completion Date :

Feb 1, 2025

Anticipated Study Completion Date :

Jul 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: NGM707 Monotherapy Dose Escalation Part 1a Single Agent Dose Escalation	Drug: NGM707 Drug: NGM707 NGM707 is given intravenously (IV) every 3 weeks in a 21 day cycle. Multiple dose levels will be evaluated.
Experimental: NGM707 Combination Dose Finding with pembrolizumab Part 1b NGM707 plus pembrolizumab	Drug: NGM707 plus pembrolizumab Drug: NGM707 NGM707 is given intravenously (IV) every 3 weeks in a 21 day cycle. Multiple dose levels will be evaluated. Drug: pembrolizumab Pembrolizumab will be administered intravenously (IV) every 3 weeks in a 21 day cycle.
Experimental: NGM707 Monotherapy Dose Expansion Arm A NGM707 in RCC	Drug: NGM707 Drug: NGM707 Preliminary recommended phase 2 dose (RP2D) of NGM707 is given intravenously (IV) every 3 weeks in a 21 day cycle.
Experimental: NGM707 Monotherapy Dose Expansion Arm B NGM707 in CRC	Drug: NGM707 Drug: NGM707 Preliminary recommended phase 2 dose (RP2D) of NGM707 is given intravenously (IV) every 3 weeks in a 21 day cycle.
Experimental: NGM707 Monotherapy Dose Expansion Arm C NGM707 in Ovarian Cancer	Drug: NGM707 Drug: NGM707 Preliminary recommended phase 2 dose (RP2D) of NGM707 is given intravenously (IV) every 3 weeks in a 21 day cycle.
Experimental: NGM707 Combination Dose Expansion Arm E NGM707 with pembrolizumab in NSCLC	Drug: NGM707 plus pembrolizumab Drug: NGM707 Preliminary recommended phase 2 dose (RP2D) of NGM707 is given intravenously (IV) every 3 weeks in a 21 day cycle. Drug: pembrolizumab Pembrolizumab will be administered intravenously (IV) every 3 weeks in a 21 day cycle.
Experimental: NGM707 Combination Dose Expansion Arm F NGM707 with pembrolizumab in SCCHN	Drug: NGM707 plus pembrolizumab Drug: NGM707 Preliminary recommended phase 2 dose (RP2D) of NGM707 is given intravenously (IV) every 3 weeks in a 21 day cycle. Drug: pembrolizumab Pembrolizumab will be administered intravenously (IV) every 3 weeks in a 21 day cycle.

Outcome Measures

Primary Outcome Measures

Number of Patients with Dose-limiting Toxicities [Baseline up to 28 Days]
A DLT is defined as an AE that meets at least one of the criteria listed in protocol, according to National Cancer Institute (NCI) common terminology criteria for AE (CTCAE) version 5.0, and is considered by the investigator to be clinically relevant and attributed to the study treatment during the first 28 days after the first dose of study treatment.
Incidence of Adverse Events [Baseline up to Approximately 24 Months]
Number of patients with adverse events (AEs) according to severity, seriousness, and relationship to study drug An AE is defined as any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of patients who experience at least one AE will be presented.
Number of Patients with Clinically Significant Laboratory Abnormalities [Baseline up to Approximately 24 Months]
Number of patients with clinically significant change from baseline in laboratory abnormalities as characterized by type, frequency, severity (graded by CTCAE version 5.0) and timing.
Number of Patients in Expansion Cohorts with Objective Responses [Baseline up to approximately 24 months]
Objective Response Rate is defined as the proportion of patients who achieve a confirmed complete response (CR) or partial response (PR) according to RECIST v1.1
Duration of Response for Patients in Expansion Cohorts [Baseline up to approximately 24 months]
Duration of Response is defined as the time from the first documentation of objective response (CR or PR) that is subsequently confirmed per RECIST v1.1, to the time of the first documentation of objective tumor progression or to death due to any cause, whichever occurs first.
Progression-free Survival for Patients in Expansion Cohorts [Baseline up to approximately 24 months]
Progression-free survival is defined as the time from start of study treatment to the date of first documentation of objective tumor progression on or following study therapy per RECIST v1.1, or to death due to any cause, whichever comes first.
Overall Survival for Patients in Combination Dose Expansion Cohorts [Up to approximately 48 months]
Overall survival is defined as the date from start of the study treatment to the date of death due to any cause.

Secondary Outcome Measures

Observed Plasma Concentration of NGM707 (Including Cmax) [Baseline up to approximately 24 months]
Will be measured on Day 1, 2, 4, 8 and 15 of Cycles 1 and 3, Day 1 of Cycle 2 and Day 1 of Cycle 4 and each cycle thereafter.
Area Under the Curve (AUC) of Plasma NGM707 [Baseline up to approximately 24 months]
Area under the curve from time zero extrapolated to the last quantifiable dose of NGM707. Time zero extrapolated to the last quantifiable time point prior to the next dose. Will be measured on Day 1, 2, 4, 8 and 15 of Cycles 1 and 3, Day 1 of Cycle 2 and Day 1 of Cycle 4 and each cycle thereafter.
Plasma Half-life (t1/2) of NGM707 [Baseline up to approximately 24 months]
Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. Will be measured on Day 1, 2, 4, 8 and 15 of Cycles 1 and 3, Day 1 of Cycle 2 and Day 1 of Cycle 4 and each cycle thereafter.
Anti-drug Antibodies (ADA) Against NGM707 [Baseline up to approximately 24 months]
Incidence and titers of anti-drug antibodies (ADA) against NGM707. Will be measured on Day 1 of each cycle.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Histologically or cytologically documented locally advanced or metastatic solid tumor malignancy.
Progressed or was intolerant to all available therapies known to confer clinical benefit appropriate for their tumor type, and for which the patient was eligible and willing to receive, or refused SOC treatments that are perceived to have marginal clinical benefit.
Adequate bone marrow, kidney and liver function.
Performance status of 0 or 1.
Resolved acute effects of any prior therapy to baseline severity or CTCAE Grade 1 except for AEs not constituting a safety risk by Investigator judgement.

Exclusion Criteria:

Prior treatment targeting ILT2 and/or ILT4 or targeting HLA-G.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Southern California	Los Angeles	California	United States	90033
2	Hoag Memorial Hospital Presbyterian	Newport Beach	California	United States	92663
3	Georgetown University Medical Center	Washington	District of Columbia	United States	20007
4	Florida Cancer Specialists - Sarasota - SCRI	Sarasota	Florida	United States	34232
5	University of Maryland Greenebaum Cancer Center	Baltimore	Maryland	United States	21201
6	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02215
7	START Midwest, LLC	Grand Rapids	Michigan	United States	49546
8	Nebraska Cancer Specialists	Omaha	Nebraska	United States	68130
9	Prisma Health - Upstate	Greenville	South Carolina	United States	29605
10	MD Anderson Cancer Center	Houston	Texas	United States	77030
11	NEXT Oncology	San Antonio	Texas	United States	78229
12	Seoul National University Hospital	Seoul		Korea, Republic of	03080
13	Samsung Medical Center	Seoul		Korea, Republic of	06351
14	National Taiwan University Hospital	Taipei		Taiwan	100225