Pancreatic CancerPhase 1NCT05311618
Study of NGM438 as Monotherapy and in Combination With Pembrolizumab in Advanced or Metastatic Solid Tumors
A Phase 1 study testing NGM438 and Pembrolizumab (KEYTRUDA ®) in people with Pancreatic Cancer and Breast Cancer, run by NGM Biopharmaceuticals, Inc at 6 sites in United States.
Trial summary
Study of NGM438 as Monotherapy and in Combination with Pembrolizumab in Advanced or Metastatic Solid Tumors Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Pancreatic Cancer, Breast Cancer, Gastric Cancer
- What is being tested?
- NGM438 and Pembrolizumab (KEYTRUDA ®)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 71 participants
- Where
- 6 sitesUnited States
- Study dates
- 11 May 2022to Jun 2025
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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 for which the patient was eligible and willing to receive.
- 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.
Who cannot join
- Prior treatment targeting LAIR1
Trial locations and contacts
6 sites in 1 country.
6 sites in 1 country
United States6 sites
SCRI Denver
Denver, Colorado, 80218
Henry Ford Health System
Detroit, Michigan, 48202
START Midwest
Grand Rapids, Michigan, 49546
MD Anderson
Houston, Texas, 77030
Yale Cancer Center
New Haven, Connecticut, 06520
Mount Sinai Hospital
New York, New York, 10029
About this study
Official title: A Phase 1/1b Dose Escalation/Expansion Study of NGM438 as Monotherapy and in Combination With Pembrolizumab in Advanced or Metastatic Solid Tumors
Study of NGM438 as Monotherapy and in Combination with Pembrolizumab in Advanced or Metastatic Solid Tumors
- Conditions
- Pancreatic Cancer, Breast Cancer, Gastric Cancer, Non Small Cell Lung Cancer, Cervical Cancer, Endocervical Cancer
- Being tested
- NGM438, Pembrolizumab (KEYTRUDA ®)
- Medical subject headings
- Pancreatic Neoplasms, Breast Neoplasms, Stomach Neoplasms, Carcinoma, Non-Small-Cell Lung, Uterine Cervical Neoplasms, Squamous Cell Carcinoma of Head and Neck, Colorectal Neoplasms, Esophageal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NGM438Drug
NGM438 is given intravenously (IV) every 3 weeks in a 21 day cycle. Multiple dose levels will be evaluated.
Pembrolizumab (KEYTRUDA ®)Drug
Pembrolizumab (KEYTRUDA®) will be administered intravenously (IV) every 3 weeks in a 21 day cycle.
| Study group | Role | What they receive |
|---|---|---|
| NGM438 Monotherapy Dose Escalation | Experimental | Part 1a Single Agent Dose Escalation Receives: Drug: NGM438 |
| NGM438 Combination Dose Finding with pembrolizumab ( KEYTRUDA ® ) | Experimental | Part 1b NGM438 plus pembrolizumab ( KEYTRUDA ® ) Receives: Drug: NGM438; Drug: Pembrolizumab (KEYTRUDA ®) |
| Biopsy Cohort with NGM438 Monotherapy Followed by Combination Therapy with Pembrolizumab(KEYTRUDA ®) | Experimental | Part 1C NGM438 followed by NGM438 plus pembrolizumab ( KEYTRUDA ® ) Receives: Drug: NGM438; Drug: Pembrolizumab (KEYTRUDA ®) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Patients with Dose-limiting Toxicities
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 21 days after the first dose of study treatment.
Measured: Baseline up to 21 Days
Number of Patients with Adverse Events
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 patient, 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.
Measured: Approximately 24 months
Number of Patients with Clinically Significant Laboratory Abnormalities
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.
Measured: Approximately 24 months
Changes in potential pharmacodynamic biomarker CD163 in paired tumor tissue in Patients in the Biopsy Cohort Summary of baseline, post baseline and changes from baseline in CD163
Measured: Baseline up to 15 days
Changes in potential pharmacodynamic biomarker MMP9 in paired tumor tissue in Patients in the Biopsy Cohort Summary of baseline, post baseline and changes from baseline in MMP9
Measured: Baseline up to 15 days
Changes in potential pharmacodynamic biomarker CD8 in paired tumor tissue in Patients in the Biopsy Cohort Summary of baseline, post baseline and changes from baseline in CD8
Measured: Baseline up to 15 days
Secondary outcomes (9)
Maximum Observed Serum Concentration (Cmax) of NGM438
Cmax is defined as the observed maximum serum concentration post drug administration.
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 Cycles 4-6 and every third cycle thereafter
Measured: Approximately 24 months. Each Cycle is 21 days.
Area Under the Curve (AUC) of Serum NGM438
Area under the curve from time zero extrapolated to the last 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 Cycles 4-6 and every third cycle thereafter
Measured: Approximately 24 months. Each Cycle is 21 days.
Time to Maximum (Tmax) Observed Serum Concentration of NGM438
Tmax is defined as the time to reach the observed maximum serum concentration (Cmax).
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 Cycles 4-6 and every third cycle thereafter
Measured: Approximately 24 months. Each Cycle is 21 days.
Half-life (t1/2) of NGM438 in Serum
Time measured for the serum concentration to decrease by one half during the terminal phase.
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 Cycles 4-6 and every third cycle thereafter
Measured: Approximately 24 months. Each Cycle is 21 days.
Systemic Clearance (CL) of NGM438
CL is defined as systemic clearance. 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 Cycles 4-6 and every third cycle thereafter
Measured: Approximately 24 months. Each Cycle is 21 days.
Volume of Distribution (Vss) of NGM438 at Steady State
Vss is defined as the volume of distribution at steady state. 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 Cycles 4-6 and every third cycle thereafter
Measured: Approximately 24 months. Each Cycle is 21 days.
Anti-drug Antibodies (ADA) Against NGM438
Incidence and titers of anti-drug antibodies (ADA) against NGM438. Will be measured on Day 1 of each cycle through Cycle 6 and every third cycle thereafter.
Measured: Approximately 24 months. Each Cycle is 21 days.
Number of Patients in Dose Escalation and Dose Finding Cohorts with Objective Responses
Objective Response Rate is defined as the proportion of patients who achieve a confirmed complete response (CR) or partial response (PR) divided by the total number of evaluable patients per RECIST v1.1
Measured: Approximately 24 months
Trough Concentrations of NGM438 in Patients in the Biopsy Cohort
Trough Concentration refers to the serum concentration of NGM438 observed just before treatment administration.
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.
Measured: Approximately 24 months. Each Cycle is 21 days.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Apr 2022
- Study start11 May 2022
- Primary completionApr 2025 (estimated)
- Study completionJun 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Pancreatic CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 71 participants (estimated)
Sponsor and investigators
- Lead sponsor
- NGM Biopharmaceuticals, Inc
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Merck Sharp & Dohme LLC
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05311618
- Sponsor's protocol ID
- 438-IO-101
- Other IDs
- KEYNOTE-E20, MK-3475-E20
- Status last verified
- Mar 2024
- First submitted
- 18 Mar 2022
- Last updated
- 1 Apr 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1/1b Dose Escalation/Expansion Study of NGM438 as Monotherapy and in Combination With Pembrolizumab in Advanced or Metastatic Solid Tumors
- ClinicalTrials.gov ID
- NCT05311618
- Acronym / sponsor ID
- 438-IO-101
- Conditions
- Pancreatic Cancer, Breast Cancer, Gastric Cancer, Non Small Cell Lung Cancer, Cervical Cancer, Endocervical Cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 71 participants (estimated)
- Lead sponsor
- NGM Biopharmaceuticals, IncIndustry (pharma, biotech, devices)
- Collaborators
- Merck Sharp & Dohme LLC
- Study start
- 11 May 2022 (actual)
- Primary completion
- Apr 2025 (estimated)
- Study completion
- Jun 2025 (estimated)
- First posted
- 5 Apr 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Study of NGM438 as Monotherapy and in Combination with Pembrolizumab in Advanced or Metastatic Solid Tumors
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| NGM438 Monotherapy Dose Escalation | Experimental | Drug: NGM438Part 1a Single Agent Dose Escalation |
| NGM438 Combination Dose Finding with pembrolizumab ( KEYTRUDA ® ) | Experimental | Drug: NGM438, Drug: Pembrolizumab (KEYTRUDA ®)Part 1b NGM438 plus pembrolizumab ( KEYTRUDA ® ) |
| Biopsy Cohort with NGM438 Monotherapy Followed by Combination Therapy with Pembrolizumab(KEYTRUDA ®) | Experimental | Drug: NGM438, Drug: Pembrolizumab (KEYTRUDA ®)Part 1C NGM438 followed by NGM438 plus pembrolizumab ( KEYTRUDA ® ) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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 for which the patient was eligible and willing to receive.
- 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.
Key exclusion criteria (1 listed)
- Prior treatment targeting LAIR1
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NGM438NGM438 is given intravenously (IV) every 3 weeks in a 21 day cycle. Multiple dose levels will be evaluated. | Drug | Biopsy Cohort with NGM438 Monotherapy Followed by Combination Therapy with Pembrolizumab(KEYTRUDA ®), NGM438 Combination Dose Finding with pembrolizumab ( KEYTRUDA ® ), NGM438 Monotherapy Dose Escalation |
| Pembrolizumab (KEYTRUDA ®)Pembrolizumab (KEYTRUDA®) will be administered intravenously (IV) every 3 weeks in a 21 day cycle. | Drug | Biopsy Cohort with NGM438 Monotherapy Followed by Combination Therapy with Pembrolizumab(KEYTRUDA ®), NGM438 Combination Dose Finding with pembrolizumab ( KEYTRUDA ® ) |
Primary outcome
Number of Patients with Dose-limiting Toxicities
Time frame: Baseline up to 21 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 21 days after the first dose of study treatment.
Number of Patients with Adverse Events
Time frame: 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 patient, 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: 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.
Changes in potential pharmacodynamic biomarker CD163 in paired tumor tissue in Patients in the Biopsy Cohort Summary of baseline, post baseline and changes from baseline in CD163
Time frame: Baseline up to 15 days
Changes in potential pharmacodynamic biomarker MMP9 in paired tumor tissue in Patients in the Biopsy Cohort Summary of baseline, post baseline and changes from baseline in MMP9
Time frame: Baseline up to 15 days
Changes in potential pharmacodynamic biomarker CD8 in paired tumor tissue in Patients in the Biopsy Cohort Summary of baseline, post baseline and changes from baseline in CD8
Time frame: Baseline up to 15 days
9 secondary outcomes
Maximum Observed Serum Concentration (Cmax) of NGM438
Time frame: Approximately 24 months. Each Cycle is 21 days.
Area Under the Curve (AUC) of Serum NGM438
Time frame: Approximately 24 months. Each Cycle is 21 days.
Time to Maximum (Tmax) Observed Serum Concentration of NGM438
Time frame: Approximately 24 months. Each Cycle is 21 days.
Half-life (t1/2) of NGM438 in Serum
Time frame: Approximately 24 months. Each Cycle is 21 days.
Systemic Clearance (CL) of NGM438
Time frame: Approximately 24 months. Each Cycle is 21 days.
Volume of Distribution (Vss) of NGM438 at Steady State
Time frame: Approximately 24 months. Each Cycle is 21 days.
Anti-drug Antibodies (ADA) Against NGM438
Time frame: Approximately 24 months. Each Cycle is 21 days.
Number of Patients in Dose Escalation and Dose Finding Cohorts with Objective Responses
Time frame: Approximately 24 months
Trough Concentrations of NGM438 in Patients in the Biopsy Cohort
Time frame: Approximately 24 months. Each Cycle is 21 days.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Apr 2024.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing NGM438 and Pembrolizumab (KEYTRUDA ®) in people with Pancreatic Cancer and Breast Cancer, run by NGM Biopharmaceuticals, Inc at 6 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 1 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Patients with Dose-limiting Toxicities (time frame: Baseline up to 21 Days). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Apr 2024.