Pamiparib Plus Surufatinib in Patients With Platinum-resistant Ovarian Cancer

Pamiparib in Combination With Surufatinib in Patients With Platinum-resistant Ovarian Cancer Who Received Prior Poly (ADP-ribose) Polymerase (PARP) Inhibitors: a Multicenter, Single-arm, Phase Ib/II Trial

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.

Study Overview

• Status: Completed
• Conditions: Ovarian Cancer; Platinum-resistant Ovarian Cancer; Primary Peritoneal Cancer; Ovarian Carcinoma; Fallopian Tube Carcinosarcoma
• Intervention / Treatment: Drug: Pamiparib; Drug: Surufatinib

• Study Type: Interventional
• Enrollment (Actual): 29
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• China
  • Guangzhou, China, 510060
    • Sun Yat-sen University Cancer Cetntre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Signed Informed Consent Form;
2. Histologically confirmed epithelial ovarian cancer, fallopian tube cancer, or primary peritoneal cancer;
3. 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;
4. Patients must have received one prior PARP inhibitor therapy, and there must be a ≥ 6 month interval since treatment;
5. Female participants age 18-75 years;
6. Has measurable lesion per RECIST v1.1;
7. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1;
8. Life expectancy ≥ 3 months;
9. Patients must have normal organ and bone marrow function;
10. 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).

Exclusion Criteria:

1. Histological diagnosis of mucinous adenocarcinoma;
2. Has received prior therapy with small molecule antiangiogenic receptor tyrosine kinase inhibitors (TKIs);
3. Known or suspected allergy to any of study drugs;
4. 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);
5. Has active ulcers, gastrointestinal perforation or obstruction;
6. Active bleeding or pathologic condition that carries a high risk of bleeding;
7. Inadequately controlled hypertension (systolic blood pressure ≥ 150 mmHg and/or diastolic blood pressure ≥ 90 mmHg) with or without treatment;
8. Major surgery within 28 days of starting study treatment;
9. Proteinuria ≥ (++) or 24 hours total urine protein > 1.0 g;
10. Uncontrolled pericardial or pleural or peritoneal effusions;
11. 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;
12. Known Human Immunodeficiency Virus (HIV) infection;
13. Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis;
14. Any medical or other condition that in the opinion of the investigator(s) would preclude the participant's participation in the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Pamiparib + Surufatinib (Phase Ib/II); 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; Oral; Other Names: Poly (ADP-ribose) polymerase (PARP) inhibitor; Drug: Surufatinib; Oral; Other Names: Tyrosine Kinase Inhibitor

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of response (DOR)	Time from first documented response (CR or PR) until documented disease progression or death, whichever occurs first.	from the first drug administration up to two years
Disease Control Rate (DCR)	Proportion of patients whose best overall response is either CR, PR, or SD.	from the first drug administration up to two years
Overall survival (OS)	Time from the date of first study treatment administration to the date of death due to any cause.	from the first drug administration up to 2 years
Safety and tolerability	Incidence, nature, and severity of adverse events graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.0.	up to 90 days after last study treatment administration
Patient Reported Outcomes (PROs)	Determination of changes in PROs with Functional Assessment of Cancer Therapy for patients with ovarian cancer (FACT-O) questionnaire	from the first drug administration up to two years
Objective response rate (ORR)	The proportion of subjects with complete response (CR) or partial response (PR) according to RECIST 1.1	from the first drug administration up to two years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Biomarkers associated with the response to pamiparib combined with surufatinib	To identify the biomarkers, including but not limited to genomic, homologous recombination deficiency (HRD), that predict the efficacy of this study treatment.	from the first drug administration up to two years

Collaborators and Investigators

• Sponsor: Sun Yat-sen University
• Collaborators: Hutchmed

Study record dates

Study Major Dates

• Study Start (Actual): September 22, 2022
• Primary Completion (Actual): June 20, 2024
• Study Completion (Actual): January 31, 2026

Study Registration Dates

• First Submitted: July 26, 2022
• First Submitted That Met QC Criteria: August 8, 2022
• First Posted (Actual): August 10, 2022

Study Record Updates

• Last Update Posted (Actual): March 10, 2026
• Last Update Submitted That Met QC Criteria: March 7, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: PARP inhibitor; Ovarian cancer; Platinum-resistant; Antiangiogenic agents
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Endocrine System Diseases; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Genital Diseases, Female; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Neoplasms, Female; Gonadal Disorders; Ovarian Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Nucleic Acids, Nucleotides, and Nucleosides; Pharmacologic Actions; Chemical Actions and Uses; Carbohydrates; Glycosides; Purines; Ribonucleotides; Nucleotides; Adenine Nucleotides; Purine Nucleotides; Polyribonucleotides; Polynucleotides; Adenosine Diphosphate Sugars; Nucleoside Diphosphate Sugars; Adenosine Diphosphate; Tyrosine Kinase Inhibitors; surufatinib; pamiparib; Poly A; Adenosine Diphosphate Ribose
• Other Study ID Numbers: B2022-348-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No