A Phase II, Single-arm, Multicenter, Prospective Study of Cardunolizumab in Recurrent or Metastatic Vulvar and Vaginal Cancer

To evaluate the efficacy and safety of cardunolizumab in combination with/without chemotherapy ± bevacizumab for recurrent or metastatic vulvar and vaginal cancers that are not amenable to radical treatment.

Study Overview

• Status: Recruiting
• Conditions: Vulvar and Vaginal Cancer
• Intervention / Treatment: Drug: Cardunolizumab

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Hanmei Lou, MD; Phone Number: +8619817462599; Email: louhm@zjcc.org.cn

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310005
      • Recruiting
      • Zhejiang Cancer Hospital
      • Contact: Hanmei Lou, MD.; Phone Number: +8619817462599; Email: louhm@zjcc.org.cn
      • Principal Investigator: Hanmei Lou, MD.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Voluntary enrolment in the study with written informed consent and ability to comply with protocol requirements visits and related procedures as specified in the protocol.
2. Age≥18 & ≤75.
3. Recurrent or metastatic vulvar and vaginal carcinoma not amenable to curative treatment, diagnosed histologically or cytologically, with a pathological type of squamous, adenocarcinoma or adenosquamous carcinoma.
4. Has at least one measurable lesion based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 assessed by investigator. Lesions located in previously irradiated areas are considered measurable if they show progression in such lesions.
5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
6. Life expectancy of at least 3 months.
7. Prior immunotherapy, targeted therapies are permitted if treatment has not been discontinued due to a grade ≥2 adverse event.
8. The end of prior systemic therapy must be ≥ 4 weeks or 5 half-lives, whichever is shorter, from the first dose of this study. and the treatment-related AE returned to CTCAE 5.0 ≤ Grade 1 (except alopecia and malaise).
9. All participants must provide an archived tumour tissue sample (formalin-fixed paraffin-embedded [FFPE] tissue wax block or a minimum of 5 unstained tumour tissue section samples, preferably newly obtained tumour tissue samples) within 2 years prior to randomisation.
10. Has adequate organ function.
11. Have agreed to take effective contraception from the date of signing the informed consent form until 120 days after the last administration.
12. Ability to understand and sign written informed consent and to comply with programme visits and related procedures.

Exclusion Criteria:

1. Participants who have received prior systemic anticancer therapy (including study drug) within 4 weeks prior to the first dose of study treatment. Note: If participants have undergone major surgery, they must have fully recovered from the toxicity and/or complications of the treatment prior to starting study treatment. Patients who require elective major surgical treatment during the study period are not eligible for enrolment.
2. Participants must have recovered to grade ≤1 or baseline level from all AEs resulting from prior treatment.
3. Received radiotherapy within 2 weeks prior to the first dose. For patients who have received radiotherapy prior to 2 weeks before the first dose, all of the following conditions must be met for enrolment: glucocorticosteroids are not required, and radiation pneumonitis, radiation hepatitis, and radiation enteritis are excluded. Patients with palliative radiotherapy to bone lesions more than 7 days from the first dose may be enrolled. Reirradiation of previously treated sites is not permitted.
4. Received an immunomodulatory drug within 2 weeks prior to randomisation.
5. Active Hepatitis B or Hepatitis C.
6. History of severe bleeding tendency or coagulation disorder.
7. Pregnant or lactating female patients.
8. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of this subject to participate, in the opinion of the treating investigator.

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: Treatment; 1.Not systematically treated: 20 patients with recurrent or metastatic vulvar and vaginal cancers enrolled without systemic treatment (platinum-based doublet chemotherapy) will be treated with cardunolizumab + platinum-based doublet chemotherapy ± bevacizumab. 2.Previous systematic treatment: Twenty patients with recurrent or metastatic vulvar and vaginal cancers previously treated with systemic therapy (platinum-based doublet chemotherapy) will be enrolled as subjects receiving cardunolizumab ± investigator's choice of chemotherapy ± bevacizumab.

Drug: Cardunolizumab; Not systematically treated:Cardunolizumab (10mg/kg) + Cisplatinum (50mg/m2)/ Carboplatinum (AUC 4-5) + Paclitaxel (175mg/m2) ± Bevacizumab (15mg/kg) for 6 cycles, every 3 weeks (Q3W), and then Cardunolizumab ± Bevacizumab Q3W maintenance treatment.; Previous systematic treatment: Cardunolizumab (10mg/kg) + Chemotherapy regimen selected by the investigator ± Bevacizumab (15mg/kg) for 6 cycles, every 3 weeks (Q3W), and then Cardunolizumab ± Bevacizumab Q3W maintenance treatment.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	ORR is defined as the proportion of subjects with confirmed CR or PR, based on RECIST v1.1.	Up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease control rate (DCR)	DCR is defined as the proportion of subjects with confirmed CR, PR, or SD, based on RECIST v1.1.	Up to 2 years
Progression-free survival (PFS)	PFS is defined as the time from the start of treatment with Cardunolizumab until the first documentation of disease progression or death due to any cause, whichever occurs first.	Up to 2 years
Overall survival (OS)	OS is defined as the time from the start of treatment with Cardunolizumab until death due to any cause.	Up to 2 years
Duration of response (DOR)	DOR is defined as the duration from the first documentation of objective response to the first documented disease progression or death due to any cause, whichever occurs first.	Up to 2 years
Adverse events (AEs)	Incidences of treatment-emergent adverse events (TEAEs) , treatment-related adverse events (TRAEs) as assessed by CTCAE v5.0	From first dose of Cardunolizumab through to 90 days after last dose of Cardunolizumab

Collaborators and Investigators

• Sponsor: Zhejiang Cancer Hospital
• Collaborators: Akeso; Innovent Biologics, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): March 22, 2024
• Primary Completion (Estimated): March 22, 2026
• Study Completion (Estimated): March 22, 2027

Study Registration Dates

• First Submitted: February 19, 2024
• First Submitted That Met QC Criteria: March 4, 2024
• First Posted (Actual): March 5, 2024

Study Record Updates

• Last Update Posted (Estimated): November 21, 2024
• Last Update Submitted That Met QC Criteria: November 20, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Keywords: Vaginal Cancer; Vulvar Cancer; Cardunolizumab
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Genital Diseases, Female; Genital Neoplasms, Female; Vaginal Diseases; Vaginal Neoplasms
• Other Study ID Numbers: IRB-2024-5(IIT)

Drug and device information, study documents

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