A Study of SHR-1210± SHR-1020 Versus Chemotherapy in Patients With Recurrent or Metastatic Cervical Cancer

NCT04680988CompletedPHASE2INTERVENTIONAL

Summary

This is a randomized, open-label, 3-arm Phase 2 study to evaluate the efficacy and safety of SHR-1210 alone or with SHR-1020 versus physician's choice chemotherapy in recurrent or metastatic cervical cancer patients. All enrolled patients will be randomly divided into 3 groups and receive treatment until disease progression, intolerable toxicity，any criterion for stopping the study drug or SHR-1210 treatment for up to 2 years.

Key Facts

Lead Sponsor

Jiangsu HengRui Medicine Co., Ltd.

Enrollment

194

Start Date

2021-04-05

Completion Date

2025-07-07

Study Type

INTERVENTIONAL

Official Title

A Randomized,Open-label, Multi-Center, Phase II Clinical Trial to Assess the Efficacy and Safety of SHR-1210± SHR-1020 Versus Physician's Choice Chemotherapy in the Treatment of Recurrent or Metastatic Cervical Cancer Patients

Interventions

SHR-1210SHR-1020Physician's choice chemotherapy

Conditions

Recurrent or Metastatic Cervical Cancer

Eligibility

Age Range

18 Years – 75 Years

Sex

FEMALE

Inclusion Criteria:

1. Voluntarily agree to participate by giving written informed consent.
2. Histologically or cytologically confirmed diagnosis of squamous-cell carcinoma, adenosquamous carcinoma, or adenocarcinoma of the cervix.
3. The patients relapsed after a platinum-based treatment regimen for recurrent or metastatic disease.
4. Patients must provide a fresh biopsy. If not, sufficient and adequate tumor tissue sample from the most recent biopsy of a tumor lesion will be required for PD-L1 expression.
5. Has measurable lesion on imaging based on RECIST version 1.1.
6. Have a life expectancy of at least 3 months.
7. ECOG performance status 0-1.
8. If childbearing potential, female patients must be willing to use at least 1 adequate barrier methods throughout the study, starting with the screening visit through 6 months after the last dose of study treatment.

Exclusion Criteria:

1. Has any malignancy \<5 years prior to study entry. Except for curative skin basal cell carcinoma, carcinoma in situ or breast cancer \>3 years.
2. Has received prior therapy with: anti-PD-1, anti-PD-L1, or anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4) antibodies; Famitinib; patient is allergic to monoclonal antibody.
3. Known to have autoimmune disease.
4. Recived other anticancer therapy 4 weeks before randomization.
5. Known to be human immunodeficiency virus positive, active hepatitis B virus, or active hepatitis C virus.
6. Untreated and/or uncontrolled brain metastases.
7. With high risk of vaginal bleeding or gastrointestinal perforation.

Outcome Measures

Primary Outcomes

Objective Response Rate (ORR) assessed by Blinded Independent Central Review in recurrent or metastatic cervical cancer patients(SHR-1210+Famitinib versus SHR-1210)

Defined as the number of subjects with a best overall response (BOR) of CR (Disappearance of all target lesions) or PR (At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters) divided by the number of measurable subjects with target lesion at baseline according to RECIST 1.1 criteria.

Time frame: Up to approximately 2 years

Secondary Outcomes

Progression free survival (PFS) in recurrent or metastatic cervical cancer patients(SHR-1210+Famitinib versus SHR-1210)

PFS is defined as from the time of randomization until the date of first documented progression or date of death from any cause, whichever came first.

Time frame: Up to approximately 2 years

Overall survival (OS) in recurrent or metastatic cervical cancer patients(SHR-1210+Famitinib versus SHR-1210)

OS is the time interval from randomization to death due to any reason or lost of follow-up.

Time frame: Up to approximately 2 years

Objective Response Rate (ORR) assessed by investigator in recurrent or metastatic cervical cancer patients(SHR-1210+Famitinib versus SHR-1210)

Defined as the number of subjects with a best overall response (BOR) of CR (Disappearance of all target lesions) or PR (At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters) divided by the number of measurable subjects with target lesion at baseline according to RECIST 1.1 criteria.

Time frame: Up to approximately 2 years

Disease control rate (DCR)，recurrent or metastatic cervical cancer patients(SHR-1210+Famitinib versus SHR-1210) according to RECIST 1.1 criteria

Defined as the number of subjects with a best overall response (BOR) of CR (Disappearance of all target lesions), PR (At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters) or SD (Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.) divided by the number of measurable subjects with target lesion at baseline according to RECIST 1.1 criteria.

Time frame: Up to approximately 2 years

Duration of response (DoR), in recurrent or metastatic cervical cancer patients(SHR-1210+Famitinib versus SHR-1210) according to RECIST 1.1 criteria.

For participants who demonstrate CR or PR, DOR is defined as the time from first documented evidence of CR or PR until disease progression or death from any cause, whichever came first. The DOR per RECIST 1.1 as assessed by Investigator will be presented.

Time frame: Up to approximately 2 years

Time to response (TTR), in recurrent or metastatic cervical cancer patients(SHR-1210+Famitinib versus SHR-1210) according to RECIST 1.1 criteria.

Defined as the time from randomization to the first objective tumor response (At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters)) observed for patients who achieved a CR or PR.

Time frame: Up to approximately 2 years

Time to treatment failure (TTF)，in recurrent or metastatic cervical cancer patients(SHR-1210+Famitinib versus SHR-1210) according to RECIST 1.1 criteria.

Defined as the time from randomization to the end of treatment or death from any cause, whichever came first.

Time frame: Up to approximately 2 years

Adverse Events (AEs)

Time frame: from the first drug administration to within 90 days for the last treatment dose

Tolerance

To calculate the proportion of dose interruption, dose reduction or dose termination because of drug-related toxicity

Time frame: from the first drug administration to within 90 days for the last treatment dose

Characteristic of Anti drug antibody

Defined as ratio of ADAs of SHR-1210 during the treatment compared to baseline.

Time frame: from the first drug administration to within 90 days for the last treatment dose

Peak Serum Concentration of SHR-1210

Defined as peak serum concentration of SHR-1210 during the treatment compared to baseline

Time frame: from the first drug administration to within 90 days for the last treatment dose

Peak Plasma Concentration of famitinib

Defined as peak plasma concentration of famitinib during the treatment compared to baseline

Time frame: from the first drug administration to within 90 days for the last treatment dose

Area under the Serum Concentration versus Time Curve of SHR-1210

Defined as area under the serum concentration versus time curve of SHR-1210 during the treatment compared to baseline

Time frame: from the first drug administration to within 90 days for the last treatment dose

Area under the Plasma Concentration versus Time Curve of famitinib

Defined as area under the plasma concentration versus time curve of famitinib during the treatment compared to baseline

Time frame: from the first drug administration to within 90 days for the last treatment dose

Locations

Fudan University Shanghai Cancer Center, Shanghai, China

Linked Papers

2025-06-25

Camrelizumab Plus Famitinib versus Camrelizumab Alone and Investigator's Choice of Chemotherapy in Recurrent or Metastatic Cervical Cancer: A Randomized, Phase II Study

PURPOSE To compare camrelizumab (an anti-PD-1 monoclonal antibody) plus famitinib (a multitarget receptor tyrosine kinase inhibitor) versus camrelizumab and chemotherapy in recurrent or metastatic cervical cancer (R/M CC). METHODS Patients with pretreated R/M CC were randomly assigned to receive camrelizumab (200 mg intravenously once every 3 weeks) plus famitinib (20 mg orally once daily), camrelizumab, or investigator's choice of chemotherapy. The primary end point was comparison of objective response rate (ORR) per blinded independent central review (BICR) for camrelizumab-famitinib versus camrelizumab in the intention-to-treat population. RESULTS Overall, 105, 54, and 35 patients received camrelizumab-famitinib, camrelizumab, and chemotherapy, respectively. As of April 21, 2023, ORR per BICR was significantly improved with camrelizumab-famitinib compared with camrelizumab (41.0% [95% CI, 31.5 to 51.0] v 24.1% [95% CI, 13.5 to 37.6]; difference, 16.9% [95% CI, 2.1 to 31.7]; one-sided P = .0181). Per investigator, ORR with camrelizumab-famitinib was 42.9% (95% CI, 33.2 to 52.9), notably higher than 22.2% (95% CI, 12.0 to 35.6) with camrelizumab and 14.3% (95% CI, 4.8 to 30.3) with chemotherapy. Median progression-free survival per investigator was prolonged with camrelizumab-famitinib than camrelizumab and chemotherapy (8.1 months [95% CI, 6.2 to 12.4] vs 4.1 months [95% CI, 2.1 to 5.1] and 2.9 months [95% CI, 2.0 to 6.2]). Median overall survival with camrelizumab-famitinib, camrelizumab, and chemotherapy, as of October 19, 2023, was 20.2 months (95% CI, 15.3 to not reached [NR]), 14.9 months (95% CI, 12.6 to NR), and 13.9 months (95% CI, 7.4 to 20.0), respectively. Eighty-nine (84.8%), eight (15.1%), and 18 (60.0%) patients who received camrelizumab-famitinib, camrelizumab, and chemotherapy, respectively, experienced grade ≥3 treatment-related adverse events. CONCLUSION Camrelizumab plus famitinib improved antitumor activity while exhibiting a manageable safety profile in patients with pretreated R/M CC, potentially offering a novel treatment option.

Linked Investigators

Hong Zhu

Li Wang

Xiaohua Wu