Overview
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.
Eligibility
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:
1. 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;
2. Have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST)
1.1.;
3. For monotherapy expansion cohort A (after the Mono-RP2D has been identified), patients
must have:
1. Gynecologic malignancies including ovarian, endometrial/uterine, fallopian tube,
cervical, vulvar, and vaginal cancers; or
2. 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).
4. 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:
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-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; Note: Patients who have progressed on
NP-G2-044 treatment prior to this study are not eligible
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, 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.