NP-G2-044: NP-G2-044 will be provided as a tablet via oral route of administration in the study.
PLD: PLD will be provided as an infusion via intravenous route of administration in the study.
Study summary
The purpose of the study is to identify the optimal dose level of NP-G2-044 in combination with standard of care (SOC) pegylated liposomal doxorubicin (PLD), and to compare the efficacy and safety of NP-G2-044+PLD vs. PLD alone in participants with platinum-resistant ovarian cancer (PROC).
Eligibility
Sex
FEMALE
Min age
18 Years
Max age
—
Healthy volunteers
No
Inclusion Criteria:
* Participants must have confirmed ovarian high-grade serous carcinoma (histologically or cytologically)
1. Participants should have platinum resistance
2. No PLD use after developing platinum resistance
3. Participants must have had bevacizumab in a prior treatment line or must have been ineligible for bevacizumab therapy.
* ECOG status 0-1
* Measurable disease per RECIST v1.1 as assessed by local site Investigator/radiologists in the Dose Escalation phase, and assessed by BICR in the Dose Optimization phase and Phase 3; lesions situated in previous irradiated areas are considered measurable if progression has been demonstrated in such lesions
* Left ventricular ejection fraction \> 50%
* Participants with adequate hematologic function based on following
1. Absolute neutrophil count ≥ 1.5 × 109/L
2. Platelet count ≥ 100 × 109/L
3. Hemoglobin ≥ 9.0 g/dL
4. Albumin ≥ 3.0 g/dL
* Adequate coagulation parameters based on the following:
1. Prothrombin time-internationalization normal rate (INR)/partial thromboplastin time \< 1.5 × upper limit of normal (ULN)
2. Partial thromboplastin time or activated partial thromboplastin time \< 1.25 × ULN
* Participants must have adequate hepatic and renal function. For hepatic function, total bilirubin should be less than 1.5 times the ULN. For renal function, serum creatinine clearance must be at least 45 mL/min.
* Participants of childbearing potential (defined as sexually mature women who have not undergone surgical sterilization or been postmenopausal for at least 12 months if over 55 years of age) must have a negative pregnancy test within 72 hours before starting treatment. These participants must use highly effective contraception or abstain from heterosexual activity from screening through 120 days after the last dose of study medication.
Exclusion Criteria:
* Primary platinum-refractory (recurrence within 120 days of first-line platinum-containing therapy or during first-line platinum-containing therapy).
* Recurrence greater than 183 days from the penultimate platinum (platinum-sensitive recurrent ovarian cancer).
* Uncontrolled malignant pleural effusions and/or ascites as defined by a prior needle drainage within 60 days of first dose.
* Major surgery within 4 weeks prior to Screening.
* Prior radiotherapy within 4 weeks of start of study treatment.
1. Participants must have recovered from all radiation-related toxicities, not require corticosteroids for their radiation therapy, and have no history of radiation pneumonitis.
2. A 1-week washout is permitted for palliative radiation (≤ 2 weeks of radiotherapy) to non-central nervous system (CNS) disease.
* Anticancer therapy, such as chemotherapy, immunotherapy, hormonal therapy, targeted therapy, or investigational agents prior to administration of the first dose of study treatment.
* Active CNS metastases; participants with leptomeningeal metastases are not eligible.
* Primary CNS malignancy.
* Severe gastrointestinal conditions such as existing bowel obstruction defined as air fluid levels in the small bowel and/or intolerance to oral medications, clinical or radiological evidence of bowel obstruction within 8 weeks prior to study entry requiring hospitalization, current use of nasogastric tube decompression, inability to tolerate solid feedings or vomiting more than once a day.
* Liver metastases involving \> 60% of liver parenchyma.
* Known active infection with Human immunodeficiency virus (HIV), Hepatitis B Virus (HBV), or Hepatitis C virus (HCV)
* Requiring immunosuppressive therapy
* Evidence of ongoing systemic bacterial, fungal, or viral infections at Screening
* Received a live vaccine within 6 weeks of first dose of study drug.
* Received a Coronavirus disease-2019 (COVID-19) vaccine less than 1 week prior to dosing (Cycle 1/Day 1) and/or during the study received a COVID-19 vaccine or booster less than 3 weeks ahead of a tumor assessment.
* Baseline QT interval corrected with Fridericia's method (i.e., QTcF) \> 470 ms.
* Female participants who are pregnant or breastfeeding.
* Concurrent active malignancy.
* History of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis which required steroid treatment.
* History of stroke, unstable angina, myocardial infarction, congestive heart failure (NYHA classification III or IV), clinically significant left ventricular hypertrophy or ventricular arrhythmia requiring medication or mechanical control within the last 6 months prior to Screening.
* Participants with increased baseline risk of Torsades de Pointe due to:
1. Electrolyte imbalance at screening (clinically significant hypokalemia, hypomagnesemia or hypocalcemia per Investigator's determination)
2. Known congenital long QT syndrome (LTQS)
3. Bradycardia (heart rate \< 50 beats per minute)
* Unstable or severe uncontrolled medical condition like unstable cardiac function, unstable pulmonary condition including pneumonitis and/or interstitial lung disease, uncontrolled diabetes or any important medical illness or abnormal laboratory findings
* Grade 3 or 4 toxicity due to PLD in prior treatment.
* Grade 2 or greater neuropathy
Primary outcome measure(s)
Part A (Dose escalation): Number of participants with adverse events (AEs) — From first dose until Safety Follow-up (30 days ±7 days after last dose of NP-G2-044) Approximately 2 years The safety and tolerability of NP-G2-044 monotherapy with BID dosing and in combination with PLD will be evaluated
Part A (Dose escalation): Number of participants with Dose Limiting Toxicities (DLTs) — Up to 28 days The safety and tolerability of NP-G2-044 monotherapy with BID dosing and in combination with PLD and to determine the recommended Phase 2 dose (RP2D) of NP-G2-044 when combined with PLD will be determined
Part B (Dose Optimization): Number of participants with AEs — From Day 1 until Safety Follow-up (30 days ±7 days after last dose of NP-G2-044) Approximately 2 years The safety and tolerability of the treatment groups will be compared.
Part B (Dose Optimization): Overall response rate (ORR) — From randomization until disease progression, death, or withdrawal of consent, whichever occurs first (Approximately 2 years) The optimal dose of NP-G2-044 combined with PLD will be evaluated. The ORR is defined as the proportion of participants with complete response (CR) or partial response (PR).
Part B (Dose Optimization): Progression free survival (PFS) — From randomization until disease progression, death, or withdrawal of consent, whichever occurs first (Approximately 2 years) The optimal dose of NP-G2-044 combined with PLD will be evaluated. The PFS is defined as time from randomization until adequately documented disease progression based on blinded independent committee review (BICR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 or death, whichever occurs first.
Part C (Phase 3): Progression free survival (PFS) — From randomization until disease progression, death, or withdrawal of consent, whichever occurs first (Approximately 3 years The efficacy of NP-G2-044 when combined with PLD vs. PLD alone will be compared. The PFS is defined as time from randomization until adequately documented disease progression based on BICR per RECIST v1.1 or death, whichever occurs first.
Trial sites (6)
Facility
City
Region
Status
HonorHealth Cancer Care
Phoenix
Arizona
Trials365
Shreveport
Louisiana
Optimum Clinical Research Group, LLC
Albuquerque
New Mexico
University of Pennsylvania Health System, Perelman Center for Advanced Medicine
Philadelphia
Pennsylvania
Utah Cancer Specialists
Salt Lake City
Utah
University Of Wisconsin Carbone Cancer Center
Madison
Wisconsin
More Novita Pharmaceuticals, Inc. trials in the USA
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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