Study of NMS-03305293 in Adult Patients With Relapsed Ovarian Cancer

NCT06930755 | Recruiting Phase 1 FDA Drug

• 1 other identifier: PARPA-293-003
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 5

Brief Summary

This is a multicenter, open-label Phase Ia/b study on the safety and efficacy of the combination of NMS-03305293 and topotecan in patients with recurrent ovarian cancer, with dose-limiting toxicity (DLT) escalation. The aim of this study is to determine the safety and tolerability, as well as to evaluate the anti-tumor efficacy and pharmacokinetics of NMS-03305293 in combination with topotecan.

Conditions

Ovarian Cancer

Outcome Measures

Primary Outcomes (1)

• Number of Participants with Adverse Events (AEs)

  Evaluation of type, frequency, severity (graded using the National Cancer Institute Common Terminology Criteria for Adverse Events \[NCI CTCAE\] Version 5.0), duration of AEs, first cycle DLT, electrocardiogram (ECG) and laboratory abnormalities and relationship of AE to study treatment

  Screening (Day ≤28) up to 28-day follow-up after end of treatment (Approximately 6 months)

Secondary Outcomes (5)

• Overall Response Rate (ORR)

  From the date of first response up to data cut-off (approximately 22 months)

• Duration of response (DoR)

  From the date of first response up to data cut-off (approximately 22 months)

• Progression-free survival (PFS)

  From the date of treatment initiation up to data cut-off (approximately 24 months)

• Overall survival (OS)

  From the date of treatment initiation up to data cut-off (approximately 24 months)

• Plasma pharmacokinetic profile of NMS-03305293 and possible identified metabolites (if appropriate) after oral administration

  Cycle 1 - Days 1, 2, 5 and 6; Cycle 2 - Days 1 & 5. Each cycle is 28 days

Study Arms (1)

NMS-03305293 and Topotecan

EXPERIMENTAL

NMS-03305293 will be administered orally, twice daily, on a 1-7-day schedule, in repeated 4-week cycles (i.e., 28 days). Topotecan will be administered intravenously (IV), once weekly, on Days 1, 8, and 15, of Weeks 1-3, in repeated 4-week cycles (i.e., 28 days) at 4 mg/m\^2 with maximum dose of 4 mg.

Drug: NMS-03305293; Drug: Topotecan

Interventions

NMS-03305293 DRUG

Route of administration: Oral

NMS-03305293 and Topotecan

Topotecan DRUG

Route of administration: Intravenous

NMS-03305293 and Topotecan

Eligibility Criteria

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

You may qualify if:

• Histologically confirmed diagnosis of high-grade serous epithelial ovarian, fallopian tube or peritoneal cancer. Sponsor might opt to restrict enrollment to either platinum refractory, primary or secondary platinum-resistant patients based on data emerging from the trial.
• Patients must have received no more than 5 prior lines of therapy and failed all evidence based local standards of care as per Investigator judgment. Sponsor might opt to restrict prio lines of therapy to 3 in any moments, based on data emerging from the trial.
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
• Patient must have progressed radiographically on or after their most recent line of anticancer therapy and have measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 (radiologically measured by the Investigator).
• Resolution of all acute toxic effects (excluding alopecia) of any prior anticancer therapy to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) (version 5.0) Grade ≤ 1 or to the baseline laboratory values as defined in the protocol
• Patients with childbearing potential must use highly effective contraception or true abstinence.

You may not qualify if:

• Current enrollment in another interventional clinical trial.
• Current treatment with other anticancer agents or devices.
• BReast CAncer gene (BRCA) mutation or homologous recombination deficiency.
• Prior therapy with PARP inhibitor, outside of approved indication and schedules. Sponsor might opt to restrict prior use of PARP inhibitor (PARPi) in any moments, based on data emerging from the trial.
• Prior therapy with topoisomerase inhibitors including payloads of Antibody-Drug Conjugates (ADCs).
• Major surgery, other than surgery for recurrent Ovarian Cancer (OC), within 4 weeks prior to treatment start.
• Patients with low-grade/borderline ovarian tumor.
• Prior anti-tumor treatment within 2 weeks prior to treatment start or 5 half-lives, whichever is longer.
• Patients with prior wide-field radiotherapy (RT) affecting at least 20 percent of the bone marrow.
• Use of full-dose anticoagulants unless the INR or activated thromboplastin time (aPTT) is within therapeutic limits (according to the medical standard in the institution) and the patient has been on a stable dose of anticoagulants for at least 2 weeks before enrollment.
• Treatment with concomitant medications known to be sensitive substrates of CYP2D6 and CYP2C19 that cannot be replaced with another treatment.
• History of interstitial lung disease or relevant lung disease in the opinion of the Investigator.
• Treatment with systemic immune modulators such as corticosteroids at prednisone equivalent dose of \> 10 mg/day, cyclosporine and tacrolimus or radiotherapy within 28 days before Cycle 1 Day 1.
• Pregnant women. All female patients with reproductive potential must have a negative pregnancy test (serum or urine) within the screening period prior to start of study drug.
• Breast-feeding women or women planning to breast feed during the study or within 3 months after study treatment.

Sponsors & Collaborators

• Nerviano Medical Sciences: lead

Study Sites (5)

OSF Saint Francis Medical Center

Peoria, Illinois, 61637, United States

RECRUITING

Washington University School of Medicine in St. Louis

St Louis, Missouri, 63130, United States

RECRUITING

Penn Medicine - Perelman Center for Advanced Medicine

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

Tennessee Oncology

Nashville, Tennessee, 37203, United States

RECRUITING

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

MeSH Terms

Conditions

Ovarian Neoplasms

Interventions

Topotecan

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

Intervention Hierarchy (Ancestors)

Camptothecin; Alkaloids; Heterocyclic Compounds

Central Study Contacts

Domenico Roberti

CONTACT

+39 0331-581111; clinicaltrials@nervianoms.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 9, 2025
• First Posted: April 16, 2025
• Study Start: April 30, 2026
• Primary Completion (Estimated): May 31, 2027
• Study Completion (Estimated): September 26, 2027
• Last Updated: March 31, 2026

Record last verified: 2026-03

Locations

US (5)