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

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. Abilty to swallow capsules and tablets;

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; Totalbilirubin ≤1.5 mg/dL; Albumin ≥3.0 g/dL; Alanine aminotransferase, aspartateaminotransferase, alkaline phosphatase, and gamma-glutamyl transferase ≤2.5 × upperlimit of normal (ULN); Creatinine clearance ≥50 mL/min; and Prothrombin time andpartial thromboplastin time ≤1.5 × ULN.

6. Female patients of childbearing potential must have a negative serum or urinepregnancy test at Screening and within 24 hours (if urine test) or 72 hours (ifserum test) before the first dose of NP-G2-044. If the urine test is positive orcannot be confirmed as negative, a serum pregnancy test will be required and must benegative for the patient to be eligible; Note: A woman is considered to bechildbearing potential unless she is postmenopausal (≥1 year without menses andconfirmed with a follicle-stimulating hormone [FSH] test) or surgically sterilizedvia bilateral oophorectomy, hysterectomy, bilateral tubal ligation, or successfulEssure® placement with a documented confirmation test at least 3 months after theprocedure.

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

8. Able to understand and voluntarily sign a written informed consent form (ICF) andwilling 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 malignancyfor which standard therapies are no longer effective, not tolerated or ineligiblefor the patient to receive;

2. Have measurable disease per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1);

3. For monotherapy expansion cohort A (after the Mono-RP2D has been identified),patients must have:

4. Gynecologic malignancies including ovarian, endometrial/uterine, fallopiantube, cervical, vulvar, and vaginal cancers; or

5. Epidermal growth factor receptor (EGFR)-high (2+ or 3+ staining per DAKOcriteria or genomic sequencing data showing 3 or more copies of the EGFR gene)triple-negative breast cancer (TNBC).

6. For Monotherapy Expansion Cohort B, patient must have advanced or metastatic solidtumors malignancy

Inclusion Criteria for NP-G2-044 Combination Therapy Patients must meet the following criteria to receive NP-G2-044 in combination with anti-PD-1 therapy in the study:

1. Have measurable disease per RECIST 1.1; For Combination Therapy Expansion Cohort A:

2. Patients must meet 1 of the following criteria to enroll in Combination TherapyExpansion Cohort A:

3. Have initiated anti-PD-(L)1 therapy in accordance with the package insert andhave been receiving the anti-PD-(L)1 therapy for ≥3 months (with therapycurrently ongoing) and have stable disease (defined either by post-treatmentonset radiographic scan or ≥3 months without radiographic or clinical evidenceof progression), or had an initial period of stable disease and now have aninitial scan demonstrating progressive disease per RECIST 1.1. or

4. Have discontinued prior anti-PD-(L)1 therapy and are now eligible for de novoNP-G2-044 plus standard of care anti-PD-1 therapy. For Combination Therapy Expansion Cohorts B through E:

5. Patients must meet 1 of the following criteria to enroll in Combination TherapyExpansion Cohorts B through E:

6. Have initiated anti-PD-(L)1 therapy. in accordance with the package insert andhave been receiving the anti-PD-(L)1 therapy for >3 months (with therapycurrently ongoing) and have stable disease (as defined above), or had aninitial period of stable disease or response and now have an initial scandemonstrating progressive disease per RECIST 1.1; or

7. Have confirmed progressive disease and discontinued prior anti-PD-(L)1 therapyand are now eligible for de novo NP-G2-044 plus standard of care anti-PD-1therapy.

8. For Combination Therapy Expansion Cohort B, patients must have cutaneous squamouscell carcinoma (CSCC) (human papilloma virus [HPV]-positive or -negative;documentation of HPV status is required);

9. For Combination Therapy Expansion Cohort C, patients must have either:

10. Esophageal squamous cell carcinoma (ESCC) (HPV-positive or -negative;documentation of HPV status is required); or

11. Oropharyngeal squamous cell carcinoma (OPSCC) (HPV-positive or -negative;documentation of HPV status is required).

12. For Combination Therapy Expansion Cohort D, patients must have non muscle invasivebladder cancer (NMIBC) meeting Bacillus Calmette-Guérin (BCG)-unresponsive criteria;

13. For Combination Therapy Expansion Cohort E, patients must have microsatelliteinstability high (MSI-H) cancer; For Combination Therapy Expansion Cohorts F and G:

14. For Combination Therapy Expansion Cohort F, patients must be immunotherapy naïve (IO naïve), have pancreatic ductal adenocarcinoma (PDAC), and meet the followingcriteria:

15. Have had stable disease or response with at least 4 months of standard of carechemotherapy;

16. Have no liver metastasis; and

17. Have albumin within the normal range at Screening and >3.5 g/dL (±10%) 3 daysbefore Cycle 1 Day 1.

18. For Combination Therapy Expansion Cohort G, patients must be I O naïve, haveplatinum resistant ovarian cancer (PROC), and meet the following criteria:

19. Had disease recurrence during or within 6 months after last administration ofplatinum-based chemotherapy; and

20. Received no more than 2 prior regimens of systemic therapy after development ofplatinum resistance.

Exclusion Criteria:

1. Received chemotherapy or radiotherapy within 4 weeks or 5 half-lives, whichever isshorter, of the first dose of NP-G2-044; Note: Prior immunotherapy is allowed forpatients receiving NP-G2-044 monotherapy. For PDAC patients in Combination TherapyExpansion Cohort F: received systemic therapy within 2 weeks of the first dose ofNP-G2-044.

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 NCICTCAE v5.0 Grade ≤1; Note: Patients who experienced a Grade ≥3 anti-PD-1-related AEper NCI CTCAE v5.0 are excluded unless recovered and approved by the Novita MedicalMonitor or designee.

3. Receiving any other investigational agent(s) or have received an investigationalagent within 4 weeks of the first dose of NP-G2-044; Note: Patients who haveprogressed on NP-G2-044 treatment prior to this study are not eligible

4. Known untreated brain metastases or treated brain metastases that have not beenradiographically and clinically stable (i.e., not requiring steroids) ≥4 weeks priorto study enrollment;

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

6. Uncontrolled intercurrent illness including, but not limited to, symptomaticcongestive heart failure, hypertension, unstable angina pectoris, cardiacarrhythmia, autoimmune or inflammatory diseases, or psychiatric illness/socialsituations that would limit compliance with study requirements;

7. Pregnant, lactating, or is planning to attempt to become pregnant or impregnatesomeone during the study or within 90 days after dosing of NP-G2-044;

8. Received prior allogenic hematopoietic stem cell transplantation or allogenic bonemarrow 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;

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

14. For PDAC patients in Combination Therapy Expansion Cohort F only: have a documentedrise in tumor markers within the last 4 months.