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

NCT07109414 | Active Not Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: NP-G2-044-P3-01GOG-3121
• Study Type: interventional
• Target: 380
• Locations: 1 country
• Sites: 6

Brief 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).

Conditions

Platinum-resistant Ovarian Cancer

Keywords

Dose escalation; Dose optimization; Small-molecule fascin inhibitor; Advanced or metastatic ovarian cancer; Randomized Phase 3

Outcome Measures

Primary Outcomes (6)

• 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

  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

  Up to 28 days

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

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

  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).

  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.

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

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

  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.

  From randomization until disease progression, death, or withdrawal of consent, whichever occurs first (Approximately 3 years

Secondary Outcomes (15)

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

  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)

  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

  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)

  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)

  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)

Study Arms (7)

Part A1 (Dose escalation):NP-G2-044 Monotherapy

EXPERIMENTAL

Participants will receive multiple doses of NP-G2-044 in tablet form orally as a monotherapy twice a daily.

Drug: NP-G2-044

Part A2 (Dose escalation): NP-G2-044+PLD combination therapy

EXPERIMENTAL

Participants will receive multiple doses of NP-G2-044 (once daily \[QD\] or BID) in tablet form orally plus a single dose of PLD as an infusion via intravenous route once in every 28 days. The recommended monotherapy doses of NP-G2-044 are determined from the results of Part A1.

Drug: NP-G2-044; Drug: PLD

Part B (Dose optimization): NP-G2-044+PLD combination dose level 1

EXPERIMENTAL

Participants will receive daily dose of NP-G2-044 in tablet form orally plus a single dose of PLD as an infusion via intravenous route once in every 28 days.

Drug: NP-G2-044; Drug: PLD

Part B (Dose optimization): NP-G2-044+PLD combination dose level 2

EXPERIMENTAL

Participants will receive daily dose of NP-G2-044 in tablet form orally plus a single dose of PLD as an infusion via intravenous route once in every 28 days.

Drug: NP-G2-044; Drug: PLD

Part B (Dose optimization) :PLD

ACTIVE COMPARATOR

Participants will receive a single dose of PLD as an infusion via intravenous route alone once in every 28 days.

Drug: PLD

Part C (Phase 3): NP-G2-044+PLD

EXPERIMENTAL

Participants will receive daily dose of NP-G2-044 in tablet form orally plus a single dose of PLD as an infusion via intravenous route once in every 28 days.

Drug: NP-G2-044; Drug: PLD

Part C (Phase 3): PLD

ACTIVE COMPARATOR

Participants will receive a single dose of PLD as an infusion via intravenous route once in every 28 days.

Drug: PLD

Interventions

NP-G2-044 DRUG

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

Also known as: Prilukae

Part A1 (Dose escalation):NP-G2-044 Monotherapy; Part A2 (Dose escalation): NP-G2-044+PLD combination therapy; Part B (Dose optimization): NP-G2-044+PLD combination dose level 1; Part B (Dose optimization): NP-G2-044+PLD combination dose level 2; Part C (Phase 3): NP-G2-044+PLD

PLD DRUG

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

Part A2 (Dose escalation): NP-G2-044+PLD combination therapy; Part B (Dose optimization) :PLD; Part B (Dose optimization): NP-G2-044+PLD combination dose level 1; Part B (Dose optimization): NP-G2-044+PLD combination dose level 2; Part C (Phase 3): NP-G2-044+PLD; Part C (Phase 3): PLD

Eligibility Criteria

• Age: 18 Years+
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants must have confirmed ovarian high-grade serous carcinoma (histologically or cytologically)
• Participants should have platinum resistance
• No PLD use after developing platinum resistance
• 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
• Absolute neutrophil count ≥ 1.5 × 109/L
• Platelet count ≥ 100 × 109/L
• Hemoglobin ≥ 9.0 g/dL
• Albumin ≥ 3.0 g/dL
• Adequate coagulation parameters based on the following:
• Prothrombin time-internationalization normal rate (INR)/partial thromboplastin time \< 1.5 × upper limit of normal (ULN)
• Partial thromboplastin time or activated partial thromboplastin time \< 1.25 × ULN

You may not qualify if:

• 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.
• Participants must have recovered from all radiation-related toxicities, not require corticosteroids for their radiation therapy, and have no history of radiation pneumonitis.
• 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

Sponsors & Collaborators

• Novita Pharmaceuticals, Inc.: lead
• Gynecologic Oncology Group: collaborator

Study Sites (6)

HonorHealth Cancer Care

Phoenix, Arizona, 85016, United States

Location

Trials365

Shreveport, Louisiana, 71133, United States

Location

Optimum Clinical Research Group, LLC

Albuquerque, New Mexico, 87109, United States

Location

University of Pennsylvania Health System, Perelman Center for Advanced Medicine

Philadelphia, Pennsylvania, 19104-5127, United States

Location

Utah Cancer Specialists

Salt Lake City, Utah, 84106, United States

Location

University Of Wisconsin Carbone Cancer Center

Madison, Wisconsin, 53792-9988, United States

Location

MeSH Terms

Conditions

Ovarian Neoplasms

Interventions

NP-G2-044; 1-dodecylpyridoxal

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders

Study Officials

• Jillian Zhang, PhD

  Novita Pharmaceuticals, Inc.

  STUDY DIRECTOR

• Lisa Barroilhet, MD

  University of Wisconsin, Madison

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 31, 2025
• First Posted: August 7, 2025
• Study Start: December 29, 2025
• Primary Completion (Estimated): October 25, 2028
• Study Completion (Estimated): October 24, 2029
• Last Updated: March 9, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (6)