Testing NM1F with Pembrolizumab in Patients with Advanced Solid Tumors

A Phase 1 Study to Investigate the Safety, Tolerability, Pharmacokinetics/Pharmacodynamics, and Antitumor Activity of NM1F as Monotherapy and in Combination With Pembrolizumab in Subjects With Locally Advanced/Metastatic Solid Tumors

This study is testing a new treatment called NM1F, both alone and with another drug called pembrolizumab, to see if it can help people with advanced solid tumors.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 38 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Hefei TG ImmunoPharma Co., Ltd. (Academic / other)
• Drugs / interventions: pembrolizumab, Chemotherapy, immunotherapy, prednisone
• Locations: 2 sites (Dallas, Texas and 1 other locations)
• Trial ID: NCT05746897 on ClinicalTrials.gov

What this trial studies

This Phase 1 study aims to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary anti-tumor activity of NM1F, both as a standalone treatment and in combination with pembrolizumab, in patients with unresectable locally advanced or metastatic solid tumors. The study is divided into two parts: one focusing on NM1F monotherapy and the other on NM1F combined with a fixed dose of pembrolizumab. Participants will undergo a screening period, followed by a treatment phase lasting up to two years, and a subsequent follow-up period.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older with unresectable locally advanced or metastatic solid tumors, such as ovarian cancer, melanoma, triple-negative breast cancer, or colorectal cancer.

Not a fit: Patients who have not progressed despite standard therapies or those with resectable tumors may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide a new treatment option for patients with advanced solid tumors that have not responded to standard therapies.

How similar studies have performed: Other studies have shown promise with similar immunotherapy approaches, but this specific combination is being explored for the first time.

Eligibility criteria

Inclusion Criteria:

1. Male or female subjects age ≥ 18 years at the time of informed consent.
2. Subjects with histologically or cytologically diagnosed unresectable locally advanced, or metastatic solid tumors, mainly but not limited to CRC, TNBC, melanoma, OC, and who have progressed despite all standard therapy or are intolerant of all standard therapy, or for whom no effective standard therapy exists
3. Subjects must have at least 1 evaluable lesion as defined by response evaluation criteria in solid tumors (RECIST) v1.1.
4. ECOG PS of 0\~2.
5. Life expectancy ≥ 3 months.
6. Subjects have sufficient baseline organ function and laboratory data.
7. Woman of childbearing potential must have a negative serum pregnancy test within 7 days prior to treatment.
8. Female subjects of childbearing potential or male subjects with a partner of childbearing potential must agree to use effective contraception at the time of informed consent and continuing through the study until 6 months after the last dose of NM1F and / or pembrolizumab.

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Exclusion Criteria:

Cancer Related

1. Subject with known active central nervous system (CNS) primary tumor or metastases.
2. History of intercurrent severe chronic or active infections.
3. Has a history of active autoimmune diseases , or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 14 days prior the first dose of study drug.
4. Has a history of symptomatic interstitial lung disease or inflammatory pneumonitis.
5. Has a history of impaired cardiac function or clinically significant cardiovascular diseases.
6. Prior allogenic or autologous bone marrow transplantation or other solid organ transplantation.
7. Has a known additional malignancy that is progressing or has required active treatment within the past 3 years (Note: Exceptions are subjects with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, and localized prostate cancer who have undergone potentially curative therapy. These subjects are not excluded).
8. Evidence of clinically significant immunosuppression such as the following:

   1. Primary immunodeficiency state such as Severe Combined Immunodeficiency Disease (SCID)
   2. Concurrent opportunistic infection
9. Presence of uncontrolled pleural effusion, pericardial effusion or ascites requiring recurrent drainage procedures (monthly or more frequently).
10. Has received prior anticancer treatment with the following therapies (specified time periods are from last dose of prior treatment to first dose of NM1F):

    1. Any therapy directed against PVRIG (COM701 or other anti-PVRIG mAb) or other CD226 axis receptor (TIGIT or CD96) at any time.
    2. Chemotherapy, target therapy, immunotherapy, or other anticancer therapy within 28 days or 5 half-lives, whichever is shorter, prior to the first dose of study treatment.
    3. Prior radiotherapy ≤ 4 weeks prior to the first dose of study treatment, with the exception of a single fraction of radiotherapy for the purposes of palliation, which is permitted.
    4. Investigational therapy: if the subject has participated in a clinical study and has received an investigational product within 4 weeks prior to the first dose of study treatment.
11. Has received systematic immunomodulatory drugs within 14 days before the first dose of study drug, such as thymosin, IL-2, IFN.
12. Has received a live vaccine within 4 weeks prior to the first dose of study drug.
13. Has a recent major surgery within 4 weeks prior to the first dose of study drug or is expected to undergo major surgery during the study.
14. Toxicities of prior therapies have not been resolved to ≤ Grade 1 or baseline as per NCI-CTCAE v5.0, except for alopecia, skin hyperpigmentation.
15. Subjects who have experienced Grade ≥ 3 irAEs from prior immunotherapies or who discontinue immunotherapy due to immune-related toxicities.
16. Has a known psychiatric or substance abuse disorder that would interfere with the subject's ability to cooperate with the requirements of the study.
17. Pregnancy or lactation. Women who are willing to discontinue breastfeeding prior to administration of study drug and do not intend to resume breastfeeding may be enrolled.
18. Has known hypersensitivity to either the drug substances or inactive ingredients in the drug product.
19. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the investigator.
20. Subjects who are unwilling or unable to comply with study procedures and study restrictions, or in the judgment of the investigator, would make the subject inappropriate for entry into this study.
21. Subjects who have contraindication for use of PD-1/PD-L1 antibody (only for Phase 1b).

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Where this trial is running

Dallas, Texas and 1 other locations

• NEXT Oncology, Dallas — Dallas, Texas, United States (Recruiting)
• Next Oncology, Virginia Cancer Specialists — Fairfax, Virginia, United States (Recruiting)

Study contacts

• Study coordinator: Xiaohu Zheng, Doctorate

Conditions Ovarian Cancer; Melanoma; Triple Negative Breast Cancer; Colorectal Cancer; solid tumors，NM1F，Pembrolizumab