NP-G2-044 as Monotherapy and Combination Therapy in Patients With Advanced or Metastatic Solid Tumor Malignancies

• Status: Recruiting
• Trial end date: 2023-09-01
• Target enrollment: 0
• Participant gender: All

Summary

Multicenter, open-label study in patients with advanced or metastatic solid tumor malignancies to evaluate the safety, tolerability, and preliminary anti-tumor efficacy, PK, and pharmacodynamics of continuously dosed NP-G2-044 monotherapy and NP-G2-044 in combination with anti-PD-(L)1 therapy.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Novita Pharmaceuticals, Inc.

Criteria

Inclusion Criteria:

1. Male or female ≥18 years of age;

2. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1;

3. Life expectancy of >6 months;

4. Able to swallow capsules;

5. Adequate organ and bone marrow function, defined by the following:

ANC >1500 cells/μL; Hemoglobin >9.0 g/dL; Platelet count >100,000 cells/μL; Total bilirubin ≤1.5 mg/dL; Albumin ≥3.0 g/dL; Alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and gamma-glutamyl transferase ≤2.5 × upper limit of normal (ULN); Serum creatinine ≤1.5 mg/dL and creatinine clearance ≥60 mL/min/1.73 m2; and Prothrombin time and partial thromboplastin time ≤1.5 × ULN.

6. Female patients of childbearing potential must have a negative serum or urine pregnancy test at Screening and within 72 hours before the first dose of NP-G2-044. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required and must be negative for the patient to be eligible; Note: A woman is considered of childbearing potential unless she is postmenopausal (≥1 year without menses and confirmed with a follicle-stimulating hormone [FSH] test) or surgically sterilized via bilateral oophorectomy, hysterectomy, bilateral tubal ligation, or successful Essure® placement with a documented confirmation test at least 3 months after the procedure.

7. Male patients must be surgically sterile or willing to use a highly effective double-barrier contraception method (eg, male condom with diaphragm or male condom with cervical cap) upon study entry, while on NP-G2-044, and for a period of at least 4 months following the last dose of NP-G2-044; and

8. Able to understand and voluntarily sign a written informed consent form (ICF) and willing and able to comply with protocol requirements.

Inclusion Criteria for NP-G2-044 Monotherapy:

Patients must meet all the following criteria to receive NP-G2-044 monotherapy in the study:

1. Have a histopathologically confirmed advanced or metastatic solid tumor malignancy that is either treatment-refractory or otherwise ineligible for treatment with standard of care agents/regimens; and

2. Have measurable disease per RECIST 1.1.

Inclusion Criterion for NP-G2-044 Combination Therapy Patients must meet the following criterion to receive NP-G2-044 in combination with anti-PD-(L)1 therapy in the study:

1. Have initiated anti-PD-(L)1 therapy in accordance with the package insert and have been receiving the anti-PD-(L)1 therapy for ≥3 months (and therapy is currently ongoing) and have stable disease, or had an initial period of stable disease and now have an initial scan demonstrating progressive disease per RECIST 1.1.

Exclusion Criteria:

1. Received chemotherapy or radiotherapy within 4 weeks or 5 half-lives, whichever is shorter, of the first dose of NP-G2-044; Note: Prior immunotherapy is allowed for patients receiving NP-G2-044 monotherapy.

2. Unresolved toxicities from previous anti-cancer therapy, defined as toxicities (other than NCI CTCAE v5.0 Grade ≤2 alopecia or neuropathy) not yet resolved to NCI CTCAE v5.0 Grade ≤1; Note: Patients who experienced a Grade ≥3 anti-PD-(L)1-related AE per NCI CTCAE v5.0 are excluded unless recovered and reviewed by the Novita Medical Monitor or designee.

3. Receiving any other investigational agent(s) or have received an investigational agent within 4 weeks of the first dose of NP-G2-044;

4. Known untreated brain metastases or treated brain metastases that have not been radiographically and clinically stable (ie, not requiring steroids) ≥4 weeks prior to study enrollment;

5. QTc by Fridericia method >470 msec or electrocardiogram (ECG) with evidence of clinically meaningful conduction abnormalities or active ischemia as determined by the Investigator;

6. Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure, hypertension, unstable angina pectoris, cardiac arrhythmia, autoimmune or inflammatory diseases, or psychiatric illness/social situations that would limit compliance with study requirements;

7. Pregnant, lactating, has been pregnant within the last 2 years, or is planning to attempt to become pregnant or impregnate someone during the study or within 90 days after dosing of NP-G2-044;

8. Received prior allogenic hematopoietic stem cell transplantation or allogenic bone marrow transplantation;

9. Received prior solid organ transplantation;

10. Ongoing immunosuppressive therapy (≥10 mg/day of prednisone or its equivalent);

11. Requires the use of a strong inhibitor or inducer of cytochrome P450 (CYP)3A4, CYP1A2, or CYP2D6 during the study;

12. History of clinically meaningful gastrointestinal bleeding, intestinal obstruction, or gastrointestinal perforation within 6 months of study enrollment; or

13. Excluded by the Sponsor due to medical history, physical examination findings, clinical laboratory results, prior medications, or other entrance criteria.