Trial of NP-G2-044 (Prilukae) Combined With PLD for Treatment of Platinum-Resistant Ovarian Cancer (ULTIMUS-1)

Phase 3RecruitingNCT07109414

Novita Pharmaceuticals, Inc.380 enrolled

Overview

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).

This is an open-label, Phase 2/3, multicenter, randomized study of NP-G2-044 in combination with PLD vs. PLD alone in participants with PROC. The Phase 2 component of the study includes a safety lead-in dose escalation of NP-G2-044 monotherapy with twice daily (BID) dosing and a dose escalation phase for NP-G2-044+PLD followed by a randomized dose optimization phase of NP-G2-044+PLD compared with PLD. In the Phase 3 component of the study, participants will be randomized to treatment with NP-G2-044+PLD, at the dose selected from the dose optimization phase, or to PLD alone. Randomized participants will be stratified according to the number of prior lines of therapy, number of prior PLD therapy lines, and region of the world. The study population is women at least 18 years of age with confirmed ovarian high grade serous carcinoma, an Eastern Cooperative Oncology Group (ECOG) status of 0-1, and whose cancer is resistant to platinum-based therapy.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

380

Conditions

Platinum-resistant Ovarian Cancer

Interventions

NP-G2-044DRUG

NP-G2-044 will be provided as a tablet via oral route of administration in the study.

PLDDRUG

PLD will be provided as an infusion via intravenous route of administration in the study.

Eligibility

Sex: FEMALEMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (5)

HonorHealth Cancer Care

Phoenix, Arizona, United States

RECRUITING

Trials365

Shreveport, Louisiana, United States

RECRUITING

University of Pennsylvania Health System, Perelman Center for Advanced Medicine

Philadelphia, Pennsylvania, United States

Outcomes

Primary Outcomes

Part A (Dose escalation): Number of participants with adverse events (AEs)

The safety and tolerability of NP-G2-044 monotherapy with BID dosing and in combination with PLD will be evaluated

Time frame: From first dose until Safety Follow-up (30 days ±7 days after last dose of NP-G2-044) Approximately 2 years

Part A (Dose escalation): Number of participants with Dose Limiting Toxicities (DLTs)

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

Time frame: Up to 28 days

Part B (Dose Optimization): Number of participants with AEs

The safety and tolerability of the treatment groups will be compared.

Time frame: From Day 1 until Safety Follow-up (30 days ±7 days after last dose of NP-G2-044) Approximately 2 years

Part B (Dose Optimization): Overall response rate (ORR)

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).

Time frame: From randomization until disease progression, death, or withdrawal of consent, whichever occurs first (Approximately 2 years)

Part B (Dose Optimization): Progression free survival (PFS)

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.

Time frame: From randomization until disease progression, death, or withdrawal of consent, whichever occurs first (Approximately 2 years)

Part C (Phase 3): Progression free survival (PFS)

Central Contacts

EVP Clinical Operation and Quality Assurance

CONTACT

312-877-2533 clinicaltrials@novita-pharm.com

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

Secondary Outcomes

Part A (Dose Escalation) and Part C (Phase 3): Overall response rate (ORR)

The initial efficacy of NP-G2-044 in combination with PLD will be evaluated. The ORR is defined as the proportion of participants with CR or PR.

Time frame: From randomization until disease progression, death, or withdrawal of consent, whichever occurs first (For Part A: Approximately 2 years; Part C: Approximately 3 years)

Part A (Dose Escalation): Progression free survival (PFS)

The initial efficacy of NP-G2-044 in combination with PLD will be evaluated. The PFS is defined as time from start of treatment until adequately documented disease progression based on local assessment of imaging studies, or death, whichever occurs first.

Time frame: From randomization until disease progression, death, or withdrawal of consent, whichever occurs first (For Part A: Approximately 2 years; Part C: Approximately 3 years)

Part A (Dose Escalation), Part B (Dose optimization) and Part C (Phase 3): Gynecologic Cancer Intergroup Cancer antigen-125 (GCIG CA-125) criteria for response

The initial efficacy of NP-G2-044 in combination with PLD will be evaluated. A response according to CA-125 has occurred if there is at least a 50% reduction in CA-125 levels from a pretreatment sample. The response must be confirmed and maintained for at least 28 days. Participants can be evaluated according to CA-125 only if they have a pretreatment sample that is at least twice the upper limit of normal and within 2 weeks prior to starting treatment. The date when the CA-125 level is first reduced by 50% is the date of the CA-125 response. To calculate CA-125 responses accurately, the following rules apply: 1) Intervening samples and the 28-day confirmatory sample must be less than or equal to (within an assay variability of 10%) the previous sample. 2) Variations within the normal range of CA-125 levels will not interfere with the response definition.

Time frame: From Screening to survival follow-up (until progression, death, or withdrawal of consent) (For Part A and B: Approximately 2 years; Part C: Approximately 3 years)

Part A (Dose Escalation), Part B (Dose optimization) and Part C (Phase 3): Overall survival (OS)

The initial efficacy of NP-G2-044 in combination with PLD will be evaluated. The OS is defined as time from start of treatment until death.

Time frame: From randomization until death For Part A and B: Approximately 2 years; Part C: Approximately 3 years)

Part A (Dose Escalation), Part B (Dose optimization) and Part C (Phase 3): Disease control rate (DCR)

The initial efficacy of NP-G2-044 in combination with PLD will be evaluated. The DCR is defined as the proportion of participants with confirmed CR, PR or stable disease (SD).

Time frame: From randomization until disease progression, death, or withdrawal of consent, whichever occurs first (For Part A and B: Approximately 2 years; Part C: Approximately 3 years)

Part A (Dose Escalation), Part B (Dose optimization) and Part C (Phase 3): Duration of response (DOR)

The initial efficacy of NP-G2-044 in combination with PLD will be evaluated. The DoR is defined as the time from first CR or PR to disease progression or death in participants who achieve CR or PR.

Time frame: From randomization until disease progression, death, or withdrawal of consent, whichever occurs first (For Part A and B: Approximately 2 years; Part C: Approximately 3 years)

Part A (Dose Escalation), Part B (Dose optimization) and Part C (Phase 3): Metastasis-free interval (MFI)

The initial efficacy of NP-G2-044 in combination with PLD will be evaluated. The MFI is defined as the time from start of treatment to confirmed occurrence of new metastasis.

Time frame: From treatment initiation to confirmed occurrence of new metastasis (For Part A and B: Approximately 2 years; Part C: Approximately 3 years)

Part A (Dose Escalation) and Part C (Phase 3): Number of participants with AEs

The safety and the tolerability of the treatment groups will be compared.

Time frame: From Day 1 until Safety Follow-up (30 days ±7 days after last dose of NP-G2-044) For Part A and B: Approximately 2 years; Part C: Approximately 3 years)

Part A (Dose Escalation), Part B (Dose optimization) and Part C (Phase 3): Participant reported outcomes based on European Organization for the Research and Treatment of Cancer Core Quality of Life Questionnaire-Ovarian Cancer Module 28 (EORTC QLQ-OV28)

The treatment groups for participant reported Quality of life (QoL) will be compared. The EORTC QLQ-OV28 will evaluate the QoL with respect to ovarian cancer. The EORTC QLQ-OV28 is specific for ovarian cancer and consists of 28 items. Each scale was scored from 0 to 100 with higher scores on the symptom scales indicating greater symptom burden.

Time frame: At screening, every 3 cycles starting Cycle 1 Day 1 (each Cyle is 28 days) For Part A and B: (Approximately 2 years; Part C: Approximately 3 years)

Part A (Dose Escalation), Part B (Dose optimization) and Part C (Phase 3): Participant reported outcomes based on European Quality of Life -5 Dimensions -5 Levels (EuroQol EQ-5D-5L)

The treatment groups for participant reported QoL will be compared. The EQ-5D-5L questionnaire assess health outcome from a wide variety of interventions on a common scale. It is comprised of 5 dimensions where each dimension has 5 levels. A higher score represents a worse outcome.

Time frame: At screening, every 3 cycles starting Cycle 1 Day 1 (each Cyle is 28 days) (For Part A and B: Approximately 2 years; Part C: Approximately 3 years)

Part A (Dose Escalation), Part B (Dose optimization) and Part C (Phase 3): Participant reported outcomes based on Functional Assessment of Cancer Therapy Ovarian Symptom Index (FOSI)

The treatment groups for participant reported QoL will be compared. The FOSI 8-item questionnaire measures response to treatment based on symptom assessment. The FOSI total score ranges from 0 (severely symptomatic) to 32 (asymptomatic).

Time frame: At screening, every 3 cycles starting Cycle 1 Day 1 (each Cyle is 28 days) (For Part A and B: Approximately 2 years; Part C: Approximately 3 years)

Part A (Dose Escalation) and Part B (Dose optimization): Terminal half-life (T1/2) of NP-G2-044 and PLD

The T1/2 of NP-G2-044 as a monotherapy with BID dosing and NP-G2-044 and PLD as combination therapy will be evaluated.

Time frame: From Day 1 to End of treatment (Approximately 2 years)

Part A (Dose Escalation) and Part B (Dose optimization): Time to maximum plasma concentration (Tmax) of NP-G2-044 and PLD

The Tmax of NP-G2-044 as a monotherapy with BID dosing and NP-G2-044 and PLD as combination therapy will be evaluated.

Time frame: From Day 1 to End of treatment (Approximately 2 years)

Part A (Dose Escalation) and Part B (Dose optimization): Maximum plasma concentration (Cmax) of NP-G2-044 and PLD

The Cmax of NP-G2-044 as a monotherapy with BID dosing and NP-G2-044 and PLD as combination therapy will be evaluated.

Time frame: From Day 1 to End of treatment (Approximately 2 years)

Part A (Dose Escalation) and Part B (Dose optimization): Area under the plasma concentration-time curve (AUC) of NP-G2-044 and PLD

The AUC of NP-G2-044 as a monotherapy with BID dosing and NP-G2-044 and PLD as combination therapy will be evaluated.

Time frame: From Day 1 to End of treatment (Approximately 2 years)