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
Overview
- Phase
- Phase 1
- Intervention
- NM1F Injection
- Conditions
- Ovarian Cancer
- Sponsor
- Hefei TG ImmunoPharma Co., Ltd.
- Enrollment
- 38
- Locations
- 2
- Primary Endpoint
- Dose-limiting Toxicity (DLT)
- Status
- Recruiting
- Last Updated
- 2 years ago
Overview
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
Detailed Description
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 (1 year and 2 years for Phase 1a and 1b, respectively, or until treatment discontinuation), and a follow-up period .
Investigators
Eligibility Criteria
Inclusion Criteria
- •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.
- •ECOG PS of 0\~
- •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.
Exclusion Criteria
- •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)
Arms & Interventions
NM1F Injection/pembrolizumab Injection
NM1F monotherapy dose escalation(Phase 1a) NM1F dose escalation in combination with a fixed dose of pembrolizumab(Phase 1b)
Intervention: NM1F Injection
NM1F Injection/pembrolizumab Injection
NM1F monotherapy dose escalation(Phase 1a) NM1F dose escalation in combination with a fixed dose of pembrolizumab(Phase 1b)
Intervention: Pembrolizumab injection
Outcomes
Primary Outcomes
Dose-limiting Toxicity (DLT)
Time Frame: First 21 days of treatment.
The incidence of DLTs during the DLT assessment period.
Dose-Finding
Time Frame: Approximately 3 years.
Determination of the MTD or maximum tested dose, and the RP2D.
Frequency and Severity of Adverse Events (AE)
Time Frame: Screening to 30 days from last dose
The incidences and percentages of patients experiencing AEs summarized by NCI CTCAE version 5.0 grade and by causality.
Secondary Outcomes
- Progression Free Survival (PFS)(Approximately 3 years.)
- Overall Survival (OS)(Approximately 3 years.)
- 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.)
- Disease Control Rate (DCR)(Approximately 3 years.)