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

• ClinicalTrials.gov Identifier: NCT04913337
• Recruitment Status: Recruiting
• First Posted: June 4, 2021
• Last Update Posted: February 10, 2023
• Sponsor: NGM Biopharmaceuticals, Inc
• Collaborator: Merck Sharp & Dohme LLC
• Information provided by (Responsible Party): NGM Biopharmaceuticals, Inc

Tracking Information

• First Submitted Date: May 20, 2021
• First Posted Date: June 4, 2021
• Last Update Posted Date: February 10, 2023
• Actual Study Start Date: June 9, 2021
• Estimated Primary Completion Date: February 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 22, 2021)

• Number of Patients with Dose-limiting Toxicities [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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.

Original Primary Outcome Measures (submitted: June 2, 2021)

• Number of Patients with Dose-limiting Toxicities [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 Expansion Cohorts of Part 2b [ Time Frame: 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.

Current Secondary Outcome Measures (submitted: September 22, 2021)

• Observed Plasma Concentration of NGM707 (Including Cmax) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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.

Original Secondary Outcome Measures (submitted: June 2, 2021)

• Observed Plasma Concentration of NGM707 (Including Cmax) [ Time Frame: Baseline up to approximately 24 months ]
  NGM707 will be measured at the end of infusion on Cycle 1 Day 1 and on days 2, 4, 8, and 15 of Cycle 1; pre-dose and end of infusion on Day 1 of Cycle 2, and every cycle thereafter.
• Area Under the Curve (AUC) of Plasma NGM707 [ Time Frame: 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. NGM707 will be measured at the end of infusion on Cycle 1 Day 1 and on days 2, 4, 8, and 15 of Cycle 1; pre-dose and end of infusion on Day 1 of Cycle 2, and every cycle thereafter.
• Plasma Half-life (t1/2) of NGM707 [ Time Frame: Baseline up to approximately 24 months ]
  Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. NGM707 will be measured at the end of infusion on Cycle 1 Day 1 and on days 2, 4, 8, and 15 of Cycle 1; pre-dose and end of infusion on Day 1 of Cycle 2, and every cycle thereafter.
• Anti-drug Antibodies (ADA) Against NGM707 [ Time Frame: Baseline up to approximately 24 months ]
  Incidence and titers of anti-drug antibodies (ADA) against NGM707. NGM707 will be measured pre-dose on Day 1 of Cycle 1, and every cycle thereafter.
• Neutralizing Antibodies (NAb) Against NGM707 [ Time Frame: Baseline up to approximately 24 months ]
  Incidence and titers of neutralizing antibodies (NAb) against NGM707. NGM707 will be measured pre-dose on Day 1 of Cycle 1, and every cycle thereafter.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study of NGM707 as Monotherapy and in Combination With Pembrolizumab in Advanced or Metastatic Solid Tumor Malignancies
• 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
• Brief Summary: Study of NGM707 as Monotherapy and in Combination with Pembrolizumab in Advanced or Metastatic Solid Tumor Malignancies
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: Non-Randomized; Intervention Model: Factorial Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• 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

Intervention

• Drug: NGM707

  Drug: NGM707

  NGM707 is given intravenously (IV) every 3 weeks in a 21 day cycle. Multiple dose levels will be evaluated.

• 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.

• Drug: NGM707

  Drug: NGM707

  Preliminary recommended phase 2 dose (RP2D) of NGM707 is given intravenously (IV) every 3 weeks in a 21 day cycle.

• 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.

Study Arms

• Experimental: NGM707 Monotherapy Dose Escalation
  Part 1a Single Agent Dose Escalation
  Intervention: Drug: NGM707
• Experimental: NGM707 Combination Dose Finding with pembrolizumab
  Part 1b NGM707 plus pembrolizumab
  Intervention: Drug: NGM707 plus pembrolizumab
• Experimental: NGM707 Monotherapy Dose Expansion Arm A
  NGM707 in RCC
  Intervention: Drug: NGM707
• Experimental: NGM707 Monotherapy Dose Expansion Arm B
  NGM707 in CRC
  Intervention: Drug: NGM707
• Experimental: NGM707 Monotherapy Dose Expansion Arm C
  NGM707 in Ovarian Cancer
  Intervention: Drug: NGM707
• Experimental: NGM707 Combination Dose Expansion Arm E
  NGM707 with pembrolizumab in NSCLC
  Intervention: Drug: NGM707 plus pembrolizumab
• Experimental: NGM707 Combination Dose Expansion Arm F
  NGM707 with pembrolizumab in SCCHN
  Intervention: Drug: NGM707 plus pembrolizumab

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: June 2, 2021): 179
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: July 2025
• Estimated Primary Completion Date: February 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: NGM Medical Director; (650) 243-5555; NGM707@ngmbio.com

• Listed Location Countries: Korea, Republic of, Taiwan, United States

Administrative Information

• NCT Number: NCT04913337
• Other Study ID Numbers: 707-IO-101; KEYNOTE-D25 ( Other Identifier: Merck Sharp & Dohme Corp )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: NGM Biopharmaceuticals, Inc
• Original Responsible Party: Same as current
• Current Study Sponsor: NGM Biopharmaceuticals, Inc
• Original Study Sponsor: Same as current
• Collaborators: Merck Sharp & Dohme LLC
• Investigators: Not Provided
• PRS Account: NGM Biopharmaceuticals, Inc
• Verification Date: August 2022