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

Study Overview
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Brief Summary
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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-1 therapy.

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

Conditions
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Advanced or Metastatic Solid Tumor Malignancies

Intervention / Treatment
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* Drug: NP-G2-044 Monotherapy
* Drug: Anti-PD-1 Therapy
* Drug: NP-G2-044 Combination therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female ≥18 years of age; Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1; Life expectancy of > 6 months; Abilty to swallow capsules and tablets; 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); Creatinine clearance ≥50 mL/min; and Prothrombin time and partial thromboplastin time ≤1.5 × ULN. Female patients of childbearing potential must have a negative serum or urine pregnancy test at Screening and within 24 hours (if urine test) or 72 hours (if serum test) 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 to be 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. 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 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: Have a histopathologically confirmed advanced or metastatic solid tumor malignancy for which standard therapies are no longer effective, not tolerated or ineligible for the patient to receive; Have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.; For monotherapy expansion cohort A (after the Mono-RP2D has been identified), patients must have: Gynecologic malignancies including ovarian, endometrial/uterine, fallopian tube, cervical, vulvar, and vaginal cancers; or Epidermal growth factor receptor (EGFR)-high (2+ or 3+ staining per DAKO criteria or genomic sequencing data showing 3 or more copies of the EGFR gene) triple-negative breast cancer (TNBC). For Monotherapy Expansion Cohort B, patient must have advanced or metastatic solid tumors malignancy Inclusion Criteria for NP-G2-044 Combination Therapy Patients must meet 1 of the following criteria to receive NP-G2-044 in combination with anti-PD-1 therapy in the study: 1. Have initiated anti-PD-1 therapy in accordance with the package insert and have been receiving the anti-PD-1 therapy for ≥3 months (with therapy 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. or Have discontinued prior anti-programmed death-1/programmed death ligand-1 (PD- [L]1) therapy and are now eligible for de novo NP-G2-044 plus standard of care anti-PD 1 therapy. Exclusion Criteria: 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. 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-1-related AE per NCI CTCAE v5.0 are excluded unless recovered and reviewed by the Novita Medical Monitor or designee. Receiving any other investigational agent(s) or have received an investigational agent within 4 weeks of the first dose of NP-G2-044; Note: Patients who have progressed on NP-G2-044 treatment prior to this study are not eligible 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; QTc by Fridericia method >470 msec or electrocardiogram (ECG) with evidence of clinically meaningful conduction abnormalities or active ischemia as determined by the Investigator; 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; Pregnant, lactating, or is planning to attempt to become pregnant or impregnate someone during the study or within 90 days after dosing of NP-G2-044; Received prior allogenic hematopoietic stem cell transplantation or allogenic bone marrow transplantation; Received prior solid organ transplantation; Ongoing immunosuppressive therapy (≥10 mg/day of prednisone or its equivalent); Requires the use of a strong inhibitor or inducer of cytochrome P450 (CYP)3A4, CYP1A2, or CYP2D6 during the study; History of clinically meaningful gastrointestinal bleeding, intestinal obstruction, or gastrointestinal perforation within 6 months of study enrollment; or Excluded by the Sponsor due to medical history, physical examination findings, clinical laboratory results, prior medications, or other entrance criteria.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NP-G2-044 Monotherapy - Capsules<br>NP-G2-044 capsules PO QD for each 28-day cycle | Drug: NP-G2-044 Monotherapy<br>* 1600 mg QD and 2100 mg QD<br>|
| Experimental: NP-G2-044 Combination Therapy With Anti-PD-1 Therapy<br>NP-G2-044 capsules PO QD for each 28-day cycle, Anti-PD-1 Therapy per standard of care, at a dose and frequency in accordance with the package insert | Drug: Anti-PD-1 Therapy<br>* previously initiated per standard of care, at a dose and frequency in accordance with the package insert<br>Drug: NP-G2-044 Combination therapy<br>* 1600 mg QD or 2100 mg QD<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Identification of the NP-G2-044 Monotherapy Recommended Phase 2 Dose (RP2D) |  | 6 months | 
| Number of incidences of Treatment Emergent Adverse Events with NP-G2-044 monotherapy | Will use NCI CTCAE v5.0 | Time of first dose of any study drug(s) until 30 days after the last dose of study drug(s) | 
| NP-G2-044 anti-tumor preliminary efficacy signals when administered as continuously dosed monotherapy assessed by RECIST 1.1 | (computed tomography [CT] or magnetic resonance imaging [MRI]) | 24 months | 
| Identification of the RP2D for patients receiving NP-G2-044 in combination with anti-PD-1 therapy |  | 9 months | 
| Number of incidences of Treatment Emergent Adverse Events with NP-G2-044 and anti-PD-1 combination therapy | Will use NCI CTCAE v5.0 | Time of first dose of any study drug(s) until 30 days after the last dose of study drug(s) | 
| NP-G2-044 anti-tumor preliminary efficacy signals when administered in combination with anti-PD-1 therapy assessed by RECIST 1.1 | (computed tomography [CT] or magnetic resonance imaging [MRI]) | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Identify and characterize preliminary anti-tumor activity of NP-G2-044 in combination with anti-PD-1 therapy | Anti-tumor activity assessed using iRECIST | 24 months | 
| Pharmacokinetics (PK) of NP-G2-044 monotherapy: AUC | Area under the plasma concentration versus time curve | 6 months | 
| Pharmacokinetics (PK) of NP-G2-044 monotherapy: Tmax | Time to peak plasma concentration | 6 months | 
| Pharmacokinetics (PK) of NP-G2-044 monotherapy: Cmax | Peak plasma concentration | 6 months | 
| Pharmacokinetics (PK) of NP-G2-044 and anti-PD-1 Combination therapy: AUC | Area under the plasma concentration versus time curve | 9 months | 
| Pharmacokinetics (PK) of NP-G2-044 and anti-PD-1 Combination therapy: Tmax | Time to peak plasma concentration | 9 months | 
| Pharmacokinetics (PK) of NP-G2-044 and anti-PD-1 Combination therapy: Cmax | Peak plasma concentration | 9 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Advanced or Metastatic Solid Tumor Malignancies