A First-in-human, Phase I, Open-label, Multicenter Study of NM1F(Anti-PVRIG) in Patients With Advanced Solid Tumors

NCT05746897 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: NM1F-T1-01
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 2

Brief Summary

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

Conditions

Ovarian Cancer; Melanoma; Triple Negative Breast Cancer; Colorectal Cancer

Keywords

solid tumors，NM1F，Pembrolizumab

Outcome Measures

Primary Outcomes (3)

• Dose-limiting Toxicity (DLT)

  The incidence of DLTs during the DLT assessment period.

  First 21 days of treatment.

• Dose-Finding

  Determination of the MTD or maximum tested dose, and the RP2D.

  Approximately 3 years.

• Frequency and Severity of Adverse Events (AE)

  The incidences and percentages of patients experiencing AEs summarized by NCI CTCAE version 5.0 grade and by causality.

  Screening to 30 days from last dose

Secondary Outcomes (8)

• Pharmacokinetics of NM1F

  Day 1 of dosing through 30 days post last dose

• Pharmacokinetics of NM1F

  Day 1 of dosing through 30 days post last dose

• Number of subjects with Anti-NM1F antibody positive .

  Day 1 of dosing through 30 days post last dose

• Objective Response Rate (ORR)

  Approximately 3 years.

• Duration of Response (DoR)

  Approximately 3 years.

Study Arms (1)

NM1F Injection/pembrolizumab Injection

EXPERIMENTAL

NM1F monotherapy dose escalation(Phase 1a) NM1F dose escalation in combination with a fixed dose of pembrolizumab(Phase 1b)

Drug: NM1F Injection; Drug: Pembrolizumab injection

Interventions

NM1F Injection DRUG

This is a Phase 1, multicenter, open-label, two-parts, FIH study to evaluate the tolerability, safety, PK/PD, and preliminary anti-tumor activity of NM1F as monotherapy and in combination with pembrolizumab (Keytruda®) in subjects with unresectable locally advanced, or metastatic solid tumors. The study consists of two parts: NM1F monotherapy dose escalation (Phase 1a), NM1F dose escalation in combination with a fixed dose of pembrolizumab (Phase 1b). For each subject in the two parts, the study will include a screening period (up to 28 days), a treatment period (until treatment discontinuation), and a follow-up period.

NM1F Injection/pembrolizumab Injection

Pembrolizumab injection DRUG

This is a Phase 1, multicenter, open-label, two-parts, FIH study to evaluate the tolerability, safety, PK/PD, and preliminary anti-tumor activity of NM1F as monotherapy and in combination with pembrolizumab (Keytruda®) in subjects with unresectable locally advanced, or metastatic solid tumors. The study consists of two parts: NM1F monotherapy dose escalation (Phase 1a), NM1F dose escalation in combination with a fixed dose of pembrolizumab (Phase 1b). For each subject in the two parts, the study will include a screening period (up to 28 days), a treatment period (until treatment discontinuation), and a follow-up period.

NM1F Injection/pembrolizumab Injection

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female subjects age ≥ 18 years at the time of informed consent.
• 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
• Subjects must have at least 1 evaluable lesion as defined by response evaluation criteria in solid tumors (RECIST) v1.1.
• ECOG PS of 0\~2.
• Life expectancy ≥ 3 months.
• Subjects have sufficient baseline organ function and laboratory data.
• Woman of childbearing potential must have a negative serum pregnancy test within 7 days prior to treatment.
• 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.

You may not qualify if:

• Cancer Related
• Subject with known active central nervous system (CNS) primary tumor or metastases.
• History of intercurrent severe chronic or active infections.
• 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.
• Has a history of symptomatic interstitial lung disease or inflammatory pneumonitis.
• Has a history of impaired cardiac function or clinically significant cardiovascular diseases.
• Prior allogenic or autologous bone marrow transplantation or other solid organ transplantation.
• 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).
• Evidence of clinically significant immunosuppression such as the following:
• Primary immunodeficiency state such as Severe Combined Immunodeficiency Disease (SCID)
• Concurrent opportunistic infection
• Presence of uncontrolled pleural effusion, pericardial effusion or ascites requiring recurrent drainage procedures (monthly or more frequently).
• Has received prior anticancer treatment with the following therapies (specified time periods are from last dose of prior treatment to first dose of NM1F):
• Any therapy directed against PVRIG (COM701 or other anti-PVRIG mAb) or other CD226 axis receptor (TIGIT or CD96) at any time.
• 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.

Sponsors & Collaborators

• Hefei TG ImmunoPharma Co., Ltd.: lead

Study Sites (2)

NEXT Oncology, Dallas

Dallas, Texas, 75039, United States

RECRUITING

Next Oncology, Virginia Cancer Specialists

Fairfax, Virginia, 22031, United States

RECRUITING

MeSH Terms

Conditions

Ovarian Neoplasms; Melanoma; Triple Negative Breast Neoplasms; Colorectal Neoplasms

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Skin Diseases; Skin and Connective Tissue Diseases; Breast Neoplasms; Breast Diseases; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Central Study Contacts

Xiaohu Zheng, Doctorate

CONTACT

+86-13956959849; xiaohu.zheng@tgimmunopharma.com

Hang Zhou, Bachelor

CONTACT

+86-15212434595; hang.zhou@tgimmunopharma.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 3, 2023
• First Posted: February 28, 2023
• Study Start: April 13, 2023
• Primary Completion (Estimated): September 30, 2027
• Study Completion (Estimated): September 30, 2027
• Last Updated: January 26, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)