Pamiparib Plus Surufatinib in Patients With Platinum-resistant Ovarian Cancer

NCT05494580 | Completed Phase 1 DMC

• 1 other identifier: B2022-348-01
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 1

Brief Summary

A number of studies suggest that the combination of PARP inhibitors and antiangiogenic agents produce synergistic activities. Pamiparib is a small molecule inhibitor selectivity for both PARP1 and PARP2. Surufatinib is a novel small-molecule inhibitor that simultaneously targets tumor angiogenesis (via Vascular Endothelial Growth Factor Receptor \[VEGFR\]1, VEGFR 2, VEGFR3 and Fibroblast Growth Factor Receptor 1 \[FGFR1\]) and immune evasion (via Colony Stimulating Factor 1 Receptor \[CSF1R\]). In this trial, we aimed to evaluate the efficacy, safety and tolerability of pamiparib in combination with surufatinib in patients with platinum-resistant ovarian cancer who received prior PARP inhibitors.

Conditions

Ovarian Cancer; Ovarian Carcinoma; Platinum-resistant Ovarian Cancer; Fallopian Tube Carcinosarcoma; Primary Peritoneal Cancer

Keywords

Ovarian cancer; PARP inhibitor; Antiangiogenic agents; Platinum-resistant

Outcome Measures

Primary Outcomes (2)

• Recommended Phase 2 dose (RP2D) (Phase Ib)

  Determine the RP2D of the pamiparib and surufatinib combination

  first 21 days of treatment

• The 6-month progression-free survival (PFS) rate (Phase II)

  The percentage of patients alive without documented progression 6 months after treatment initiation.

  from the first drug administration up to two years

Secondary Outcomes (6)

• Objective response rate (ORR)

  from the first drug administration up to two years

• Disease Control Rate (DCR)

  from the first drug administration up to two years

• Duration of response (DOR)

  from the first drug administration up to two years

• Overall survival (OS)

  from the first drug administration up to 2 years

• Safety and tolerability

  up to 90 days after last study treatment administration

Other Outcomes (1)

• Biomarkers associated with the response to pamiparib combined with surufatinib

  from the first drug administration up to two years

Study Arms (1)

Pamiparib + Surufatinib (Phase Ib/II)

EXPERIMENTAL

Phase Ib: A dose de-escalation schedule is used in the phase Ib dose finding part. Dose Level 1 (starting dose): pamiparib 40 mg administered orally twice daily (fixed dose) and surufatinib 250 mg administered orally once daily on a 21-day treatment cycle. If ≥2/6 patients experience a dose limiting toxicity (DLT), we will de-escalate to Dose Level 2: pamiparib 40 mg administered orally twice daily (fixed dose) and surufatinib 200 mg administered orally once daily on a 21-day treatment cycle. Approximately 3-12 patients will be enrolled in phase Ib study. Phase II: The phase II part will begin once the recommended phase 2 dose (RP2D) of surufatinib have been determined in the Phase Ib in order to assess antitumor activity of pamiparib and surufatinib combination. In phase II study, pamiparib 40 mg orally twice daily and surufatinib PR2D will be administered.

Drug: Pamiparib; Drug: Surufatinib

Interventions

Pamiparib DRUG

Oral

Also known as: Poly (ADP-ribose) polymerase (PARP) inhibitor

Pamiparib + Surufatinib (Phase Ib/II)

Surufatinib DRUG

Oral

Also known as: Tyrosine Kinase Inhibitor

Pamiparib + Surufatinib (Phase Ib/II)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed Informed Consent Form;
• Histologically confirmed epithelial ovarian cancer, fallopian tube cancer, or primary peritoneal cancer;
• Platinum-resistant disease, defined as progression within 6 months from completion of most recent platinum-containing therapy. Subject may have been treated with additional regimen(s) subsequent to determination of platinum resistance;
• Patients must have received one prior PARP inhibitor therapy, and there must be a ≥ 6 month interval since treatment;
• Female participants age 18-75 years;
• Has measurable lesion per RECIST v1.1;
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1;
• Life expectancy ≥ 3 months;
• Patients must have normal organ and bone marrow function;
• Women of childbearing potential should have a negative serum or urine pregnancy test prior to receiving the first dose of study treatment; and should be willing to use one acceptable contraception (i.e., oral contraceptives, condoms, intrauterine devices \[IUDs\]) throughout the period of taking study treatment and for at least 6 months after the last dose of study drug(s).

You may not qualify if:

• Histological diagnosis of mucinous adenocarcinoma;
• Has received prior therapy with small molecule antiangiogenic receptor tyrosine kinase inhibitors (TKIs);
• Known or suspected allergy to any of study drugs;
• Has clinically significant cardiovascular disease within 6 months from first dose of study intervention, including New York heart association \[NYHA\] class \> 2, unstable angina, myocardial infarction, cardiac arrhythmia associated with hemodynamic instability (including corrected QT (QTc) interval ≥ 450 ms in men, ≥ 470 ms in female);
• Has active ulcers, gastrointestinal perforation or obstruction;
• Active bleeding or pathologic condition that carries a high risk of bleeding;
• Inadequately controlled hypertension (systolic blood pressure ≥ 150 mmHg and/or diastolic blood pressure ≥ 90 mmHg) with or without treatment;
• Major surgery within 28 days of starting study treatment;
• Proteinuria ≥ (++) or 24 hours total urine protein \> 1.0 g;
• Uncontrolled pericardial or pleural or peritoneal effusions;
• Has a diagnosed and/or treated additional malignancy within the last 5 years. Exceptions include in situ cervical cancer, non-melanoma skin cancer, or superficial bladder tumors that has undergone potentially curative therapy;
• Known Human Immunodeficiency Virus (HIV) infection;
• Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis;
• Any medical or other condition that in the opinion of the investigator(s) would preclude the participant's participation in the study.

Sponsors & Collaborators

• Sun Yat-sen University: lead
• Hutchmed: collaborator

Study Sites (1)

Sun Yat-sen University Cancer Cetntre

Guangzhou, 510060, China

Location

MeSH Terms

Conditions

Ovarian Neoplasms

Interventions

pamiparib; Poly A; Adenosine Diphosphate Ribose; surufatinib; Tyrosine Kinase Inhibitors

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)

Polyribonucleotides; Polynucleotides; Nucleotides; Nucleic Acids, Nucleotides, and Nucleosides; Adenosine Diphosphate Sugars; Adenosine Diphosphate; Adenine Nucleotides; Purine Nucleotides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Nucleoside Diphosphate Sugars; Glycosides; Carbohydrates; Ribonucleotides; Protein Kinase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof.

Model Details: Drug: Pamiparib Drug: Surufatinib

Study Record Dates

• First Submitted: July 26, 2022
• First Posted: August 10, 2022
• Study Start: September 22, 2022
• Primary Completion: June 20, 2024
• Study Completion: January 31, 2026
• Last Updated: March 10, 2026

Record last verified: 2026-03

Locations

CN (1)