A Phase 1/2 Study of NGM707 as Monotherapy and in Combination with Pembrolizumab in Advanced or Metastatic Solid Tumors

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Ngm Biopharmaceuticals Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

completed 14 Jan 2025

Decision date (initial)

2023-07-10

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

NGM Biopharmaceuticals Inc.

External identifiers

EU CT number

2022-503060-33-00

WHO UTN

U1111-1288-3716

ClinicalTrials.gov

NCT04913337

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

• To evaluate antitumor activity of NGM707 in combination with pembrolizumab
• To assess the safety and tolerability of NGM707 in combination with pembrolizumab

Secondary objectives 3

1. To evaluate NGM707 drug concentration data in patients following administration
2. To evaluate the immunogenicity of NGM707
3. To evaluate the immunogenicity of NGM707 in combination with pembrolizumab

Conditions and MedDRA coding

Advanced or Metastatic Solid Tumor Malignancies

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 14

1. Males or females ≥18 years of age who comprehend and are willing and able to provide an ICF, and able to comply with scheduled visits, treatment schedule, and laboratory tests, including the other requirements for the study.
2. Histologically or cytologically documented locally advanced or metastatic solid tumor malignancy (see specific histology types for each part of study below)
3. Patients must not be amenable to local therapy with curative intent (surgery or radiation therapy with or without chemotherapy)
4. ECOG PS of ≤1.
5. Adequate bone marrow function, including: • ANC ≥1500/µL • Platelets ≥100×10³/µL. For Part 1c only, platelets ≥75×10³/µL without transfusion. • Hemoglobin ≥9.0 g/dL. Limited transfusion to reach this value are allowed after discussion with Sponsor’s Medical Monitor. There should not be a chronic need for transfusion in the recent past (approximately 3 months).
6. Adequate liver function, including: • Total bilirubin ≤1.5×ULN (except patients with Gilbert syndrome who must have total bilirubin <3.0 mg/dL). For Part 1c only, total bilirubin ≤3×ULN. • AST ≤2.5×ULN (if patient has known liver metastases or for Part 1c, then ≤5×ULN) • ALT ≤2.5×ULN (if patient has known liver metastases or for Part 1c, then ≤5×ULN)
7. Adequate renal function, including serum creatinine ≤1.5×ULN or estimated CrCl ≥40 mL/min/ ≥50 mL/min for Part 1c as calculated using the method standard for the institution. In equivocal cases, a 24 hour urine collection test can be used to estimate the CrCl more accurately
8. International normalized ratio (INR) or activated partial thromboplastin time (aPTT) <1.5×ULN or <2×ULN for Part 1c unless participant is receiving anticoagulation therapy as long as PT or aPTT is within the therapeutic range of intended use of anticoagulants.
9. Resolved acute effects of any prior therapy to baseline severity or CTCAE Grade 1 in accordance with CTCAE v5.0 except for AEs not constituting a safety risk by Investigator judgement
10. Women of childbearing potential must agree to use of 2 methods of acceptable contraception from screening until 4 months after the last dose of study drug (see Section 5.4). Acceptable methods of contraception are defined as those that result, alone or in combination, in a low failure rate (ie, less than 1% per year) when used consistently and correctly, such as surgical sterilization, an intrauterine device, or hormonal contraception in combination with a barrier method. In certain countries (if permitted by law), women of childbearing potential may agree to abide by heterosexual sexual abstinence during the time of participation in this study.
11. Males who are sexually active with a female partner of childbearing potential must agree to use a barrier contraception (eg, condom with spermicidal foam/gel/film/cream/suppository) from screening until 4 months following the last dose of study drug, in addition to their female partner using either an intrauterine device or hormonal contraception and continuing until 4 months following the last dose of study drug. This criterion may be waived for male patients who have had a vasectomy >6 months before signing the ICF.
12. An archival tumor biopsy must be provided and should be taken within 1 year of enrollment. If not available, a fresh tumor biopsy is acceptable (see Section 8.7.2.2).
13. Part 2b Have at least 1 measurable lesion per RECIST v1.1 criteria.
14. Part 2b Disease cohort specific criteria as follows: • Cohort A (2L or 3L Squamous NSCLC) - Histologically or cytologically confirmed diagnosis of advanced/metastatic NSCLC (squamous cell carcinoma subtype); mixed histology (e.g., adeno-squamous) is allowed if there is predominant squamous cell histology in the biopsy specimen. - Received prior anti- PD(L)1-directed therapy plus/minus platinum- or pemetrexedbased doublet chemotherapy, either as combination or in any sequence. No more than 2 prior lines of systemic therapy allowed. • Cohort B (2L or 3L Non-Squamous NSCLC) - Histologically or cytologically confirmed diagnosis of advanced/metastatic NSCLC (predominant cell histology of adenocarcinoma in the biopsy specimen). - Received prior anti- PD(L)1-directed therapy plus/minus platinum- or pemetrexedbased doublet chemotherapy, either as combination or in any sequence. No more than 2 prior lines of systemic therapy allowed. • Cohort C (2L or 3L SCCHN) - Histologically confirmed diagnosis of primary tumor location of oral cavity, oropharynx, hypopharynx, or larynx. Patient may not have a primary tumor site of nasopharynx (any histology). Results from testing of HPV status assessed by P16 with initial diagnosis must be available and recorded for oropharyngeal cancer patients. - Provide fresh baseline biopsy during the screening period. - Received prior anti-PD(L)1-directed therapy plus/minus chemotherapy, either as combination or in any sequence. No more than 2 prior lines of systemic therapy allowed.

Exclusion criteria 21

1. History of prior malignancy other than the cancer under treatment in this study, except for adequately treated in situ cancer, basal cell, or squamous cell skin cancer, or other cancers (eg, breast, prostate) for which the patient has been disease‑free for at least 3 years.
2. Active brain or leptomeningeal metastasis. Patients with known brain metastases are eligible if they have been treated and MRI shows no evidence of progression for at least 8 weeks after treatment is completed and within 3 weeks prior to first dose of study drug. Patients are not eligible if they require high dose of systemic corticosteroids that could result in immunosuppression (>10 mg/day prednisone equivalents) for at least 2 weeks prior to study drug administration
3. Treatment with anti neoplastic therapy (including but not limited to cytotoxic chemotherapy, major surgery, radiation, biologic agents, and investigational agents) within 28 days or <5× elimination half life, whichever is earlier, before the first dose of study drug
4. Major surgery defined as any surgical procedure that involves general anesthesia and a significant incision (ie, larger than what is required for the placement of a central venous access, percutaneous feeding tube, or biopsy) within 28 days of first dose of NGM707, or anticipated surgery during the study.
5. Radiation therapy with treatment intent within 4 weeks prior to the first dose of study drug. Any palliative radiation therapy completed within the 7 days prior to Day 1 of study drug administration is exclusionary
6. Females who are pregnant or breastfeeding
7. Prior treatment targeting ILT2 and/or ILT4 or targeting HLA G
8. Patients with active, uncontrolled bacterial, fungal, or viral infection, including HBV, HCV, known HIV, or AIDS related illness. In equivocal cases, patients whose viral load is negative may be eligible. Note: criteria for patients with HCC in Part 1c are defined separately in the protocol
9. HIV-infected participants with a history of Kaposi sarcoma and/or Multicentric Castleman Disease.
10. Active bleeding disorder, including gastrointestinal bleeding, as evidenced by hematemesis, significant hemoptysis, or melena in the past 6 months
11. History of allergy or known hypersensitivity to study drug components originated from CHO cells.
12. Inadequately controlled arterial hypertension (approximately above 150 or 100 mmHg in systolic and diastolic pressure, respectively). Consult the Sponsor with any questions. Anti hypertensive therapy to achieve these parameters is allowable
13. Patients with a history of interstitial lung disease/non infectious pneumonitis that required steroid, radiation pneumonitis, active pulmonary tuberculosis, or evidence of active pneumonitis on screening chest CT scan. Patients with radiation therapy to the lung that is >30 Gy within 6 months of the first dose of treatment are excluded. Patients with active lung infections requiring treatment are also excluded.
14. Baseline 12 lead ECG that demonstrates clinically relevant abnormalities that may affect patient safety or interpretation of study results (eg, baseline QTcF interval >470 msec, complete LBBB, signs of an acute or indeterminate age myocardial infarction, ST T interval changes suggestive of active myocardial ischemia, second or third degree AV block, or serious bradyarrhythmias or tachyarrhythmias). - If the baseline uncorrected QT interval is >470 msec, this interval should be rate corrected using the QTcF and the resulting QTcF should be used for decision making and reporting (additional details are in the protocol)
15. Any of the following in the previous 6 months: cerebrovascular accident, transient ischemic attack, symptomatic pulmonary embolism, and/or other clinically significant episodes of thromboembolic disease. Venous thromboembolic events that are non–life threatening and stable on low molecular weight heparin or factor Xa inhibitors that can be reversed by andexanet α are allowed.
16. Any of the following in the previous 6 months: myocardial infarction, symptomatic congestive heart failure (NYHA Class >II; see Appendix 2), unstable angina, coronary/peripheral artery bypass graft, or unstable cardiac arrhythmia requiring medication. Ongoing cardiac dysrhythmias of National Cancer Institute (NCI) CTCAE > Grade 2, atrial fibrillation of any grade (> Grade 2 in the case of asymptomatic lone atrial fibrillation). Patients with LVEF <45% as measured by screening echocardiogram or MUGA are not eligible. Patients with cardiac rhythm device/pacemaker must be discussed in detail with Sponsor’s Medical Monitor to judge eligibility
17. Clinically significant and unmanageable ascites defined as requiring constant therapeutic paracentesis (limited medical treatment to control ascites is permitted, but all patients who received paracentesis within 3 months of expected first dosing date will require review by Sponsor’s Medical Monitor).
18. Any condition including medical, emotional, psychiatric, or logistical that, in the opinion of the Investigator, would preclude the patient from adhering to the protocol
19. Has received a live or live-attenuated vaccine within 30 days prior to the first dose of study drug. Note: Administration of killed vaccines are allowed.
20. Has had an allogeneic tissue/solid organ transplant
21. Part 2b Have a life expectancy of <3 months or rapid progression of disease in the opinion of the Investigator.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. " Treatment-emergent AEs characterized by type, frequency, severity (graded by NCI CTCAE v5.0), timing, seriousness, and relationship to study drug"
2. " Objective tumor response (ORR) as per RECIST v1.1"

Secondary endpoints 3

1. " Trough concentrations of NGM707 for selected cycles"
2. " Incidence and titers of ADA and nAb against NGM707"
3. " DCR, DOR, PFS as per RECIST v1.1 as assessed by the Investigator and overall survival "

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Ngm Biopharmaceuticals Inc.

Sponsor organisation

Ngm Biopharmaceuticals Inc.

Address

333 Oyster Point Boulevard

City

South San Francisco

Postcode

94080-1978

Country

United States

Scientific contact point

Organisation

Ngm Biopharmaceuticals Inc.

Contact name

Vladimir Hanes

Public contact point

Organisation

Ngm Biopharmaceuticals Inc.

Contact name

Vladimir Hanes

Third parties 10

Locations

3 EU/EEA countries · 11 investigational sites

By country

Investigational sites

Application history

1 submissions — initial application plus substantial / non-substantial modifications