Famitinib Plus Anti-PD1 Therapy for Advanced Urinary System Tumor, Advanced Gynecological Tumors

• ClinicalTrials.gov Identifier: NCT03827837
• Recruitment Status: Recruiting
• First Posted: February 4, 2019
• Last Update Posted: July 1, 2022
• Sponsor: Jiangsu HengRui Medicine Co., Ltd.
• Information provided by (Responsible Party): Jiangsu HengRui Medicine Co., Ltd.

Tracking Information

• First Submitted Date: November 12, 2018
• First Posted Date: February 4, 2019
• Last Update Posted Date: July 1, 2022
• Actual Study Start Date: January 23, 2019
• Estimated Primary Completion Date: December 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 31, 2019)

Overall response rate (ORR) [ Time Frame: Up to 2 years ]

Defined as complete or partial response per RECIST 1.1 criteria with assessment every 9 weeks

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: January 31, 2019)

• Duration of Response (DoR) [ Time Frame: Up to 2 years ]
  Duration of Response (DoR) per RECIST 1.1
• Disease Control Rate (DCR) [ Time Frame: Up to 2 years ]
  Disease Control Rate per RECIST 1.1
• Time to objective response(TTR) [ Time Frame: Up to 2 years ]
  Time to objective response per RECIST 1.1
• Progression-free survival(PFS) [ Time Frame: Up to 2 years ]
  Progression-free survival(PFS) per RECIST 1.1
• Overall survival(OS) [ Time Frame: Up to 2 years ]
  Overal Survial will be calculated based on Kaplan-Meier estimates
• 12-month survival rate [ Time Frame: Up to 1 year ]
  12-month survival rate will be calculated based on Kaplan-Meier estimates of Overall survival at 12 months
• number of participants who experience an adverse event (AE) [ Time Frame: From the first assignment of informed consent form up to 90 days after the last dose ]
  number of participants who experience an adverse event (AE) per CTCAE 4.03
• serum SHR-1210 concentrations [ Time Frame: From the first dose up to 30 days after the last dose ]
  serum SHR-1210 concentrations
• Positive rate of ADA [ Time Frame: From the first dose up to 30 days after the last dose ]
  Positive rate of anti-SHR1210 antibody
• Maximum Observed Plasma Concentration (Cmax) [ Time Frame: Day 1 of cycle 3 (each cycle is 21 days) ]
  Cmax, based PK parameters
• Time to Reach Maximum Observed Plasma Concentration (Tmax) [ Time Frame: Day 1 of cycle 3 (each cycle is 21 days) ]
  Summarized by dose, cycle, day and time
• Apparent Oral Clearance (CL/F) [ Time Frame: Day 1 of cycle 3 (each cycle is 21 days) ]
  Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Famitinib Plus Anti-PD1 Therapy for Advanced Urinary System Tumor, Advanced Gynecological Tumors
• Official Title: Famitinib Malate Plus Anti-PD1 Therapy (SHR-1210) in Advanced Renal Cell Carcinoma, Urothelial Carcinoma, Advanced Cervical Cancer, Relapse Ovarian Cancer, Endometrial Cancer: Multi-institutional, Open-label, Phase 2 Trial

Brief Summary

Phase II multi-chort, adaptive two-stage, open label, nonrandomized study. The aim of our study is to evaluate the efficacy and safety of anti-PD-1 antibody SHR-1210(Camrelizumab) in combination with a small-molecule multikinase inhibitor Famitinib in subjects with advanced RCC/UC/CC/EC and recurrent OC.

chort1: Renal Cell Carcinoma (RCC) chort2: Urothelial Carcinoma(UC) chort3: Ovarian Cancer (OC) chort4: Cervical Cancer (CC) chort5: Endometrial Cancer (EC)

• Detailed Description: Stage 1: Approximately 110 participants will be recruited, 22 participants per chort; Stage 2: Approximately 55 participants will be recruited, 11 participants per chort, if more than 7（including 7） patients reached ORR in every chort ; Approximately 155 participants will be recruited, 21 participants per chort, if 3 ≤ patients <7 patients reached ORR in every chort.
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Renal Cell Carcinoma
• Urothelial Carcinoma
• Cervical Cancer
• Ovarian Cancer Recurrent
• Endometrial Cancer

Intervention

• Biological: SHR-1210
  SHR-1210 is a humanized anti-PD1 IgG4 monoclonal antibody
  Other Name: Camrelizumab
• Drug: Famitinib
  a small-molecule multikinase inhibitor
  Other Name: Famitinib Malate Capsule

Study Arms

Experimental: SHR-1210 combined with Famitinb

SHR-1210 + Famitinib

Interventions:

• Biological: SHR-1210
• Drug: Famitinib

Publications *

• Qu YY, Sun Z, Han W, Zou Q, Xing N, Luo H, Zhang X, He C, Bian XJ, Cai J, Chen C, Wang Q, Ye DW. Camrelizumab plus famitinib for advanced or metastatic urothelial carcinoma after platinum-based therapy: data from a multicohort phase 2 study. J Immunother Cancer. 2022 May;10(5):e004427. doi: 10.1136/jitc-2021-004427.
• Xia L, Peng J, Lou G, Pan M, Zhou Q, Hu W, Shi H, Wang L, Gao Y, Zhu J, Zhang Y, Sun R, Zhou X, Wang Q, Wu X. Antitumor activity and safety of camrelizumab plus famitinib in patients with platinum-resistant recurrent ovarian cancer: results from an open-label, multicenter phase 2 basket study. J Immunother Cancer. 2022 Jan;10(1):e003831. doi: 10.1136/jitc-2021-003831.

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: January 31, 2019): 265
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 2022
• Estimated Primary Completion Date: December 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Be willing and able to provide written informed consent/ for the trial.
2. Be at least 18 years of age on day of signing informed consent, male or female.

3. Patients with one of the following tumors:

   • Histologically or cytologically confirmed diagnosis of advanced renal cell carcinoma (defined as more than 50% clear cell component) after failure of IL-2 and/or anti-VEGF TKI treatment. If patients didn't want to use anti-VEGF TKI medicine or couldn't stand anti-VEGF TKI medicine costs, they will also be considered.
   • Histologically or cytologically confirmed diagnosis of unresectable urothelial carcinoma of the renal pelvis, ureter, bladder, or urethra (defined as more than 50% transitional cell component) after failure of no more than two prior platinum-based chemotherapeutic regimen.
   • Histologically or cytologically confirmed diagnosis of advanced squamous cell carcinoma of the cervix after failure of first-line system treatment.
   • Histologically confirmed diagnosis of recurrent or refractory epithelial ovarian cancer, fallopian tube cancer or primary peritoneal cancer that are relapsed and resistant (recurred less than 6 months after chemotherapy) or refractory (progressed on chemotherapy) to prior platinum-based standard care systemic regimen.
   • Histologically confirmed diagnosis of recurrent or refractory endometrial cancer that are relapsed and resistant or refractory (progressed on chemotherapy) to prior platinum-based standard care systemic regimen.
4. At least one measurable lesion according to RECIST 1.1.
5. The patients can swallow pills.
6. Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1.
7. Life expectancy of at least 12 weeks.
8. The results of patients' blood tests are as follows:-Neutrophils≥1.5E+9/L; - Plt≥90E+9/L; -Hb≥90g/L; -ALB≥30g/L ;-TSH≤1×ULN;-TBIL ≤ 1 ×ULN;-ALT and AST ≤ 3 ×ULN; AKP≤ 2.5×ULN; -Creatinine ≤ 1.5×ULN.
9. Male or Female patient of childbearing potential (entering the study after a menstrual period and who have a negative pregnancy test), who agrees to use two methods (one for the patient and one for the partner) of medically acceptable forms of contraception during the study and for 3 months after the last treatment intake.

Exclusion Criteria:

1. Patients with any active autoimmune disease or history of autoimmune disease, including but not limited to the following: hepatitis, pneumonitis, uveitis, colitis (inflammatory bowel disease), hypophysitis, vasculitis, nephritis, hyperthyroidism, and hypothyroidism, except for subjects with vitiligo or resolved childhood asthma/atopy. Asthma that requires intermittent use of bronchodilators or other medical intervention should also be excluded.
2. Concurrent medical condition requiring the use of immunosuppressive medications, or immunosuppressive doses of systemic or absorbable topical corticosteroids. Doses > 10 mg/day prednisone or equivalent are prohibited within 2 weeks before study drug administration.
3. Known history of hypersensitivity to other antibody formulation.
4. Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 2 weeks prior to trial treatment.
5. Hypertension and unable to be controlled within normal level following treatment of anti-hypertension agents: systolic blood pressure ≥140 mmHg, diastolic blood pressure ≥ 90 mmHg.
6. Clinically significant cardiovascular and cerebrovascular diseases, including but not limited to（1）Congestive heart failure (New York heart association (NYHA) class > 2)；（2）unstable or severe angina; （3）myocardial infarction within 12 months before enrollment；（4） ventricular arrhythmia which need medical intervention.（5）QTc>450ms（male）/QTc>470ms (female)；
7. Coagulation abnormalities (INR>2.0、PT>16s), with bleeding tendency or are receiving thrombolytic or anticoagulant therapy.
8. Bleeding history, having bleeding event（≥3 Grade according CTCAE 4.0 ）within 4 weeks before screening.
9. Tumor invasion around major vessels shown by imaging, high risk of major vascular invasion leading to massive hemorrhage judged by investigators.
10. Previous Arterial/venous thrombosis events within 6 months.
11. Known hereditary or acquired bleeding and thrombosis tendency.
12. Proteinuria ≥ (++) and 24 hours total urine protein > 1.0 g.
13. Prior chemotherapy, radiotherapy, surgery therapy within 4 weeks or palliative radiotherapy within 2 weeks or target therapy within 5 half-life of the drug before the study drug administration, or any unresolved AEs > Common Terminology Criteria for Adverse Events (CTCAE) Grade 1.
14. Active infection or an unexplained fever > 38.5°C within 7 days before the study drug administration, or baseline WBC>15×E+9/L .
15. Has known history of Interstitial lung disease, or using steroids evidence of active, non-infectious pneumonitis, or would interfere with the detection and handling of suspicious drug-related pulmonary toxicity.
16. History of immunodeficiency or human immunodeficiency virus (HIV) infection.
17. HBV DNA>500 IU/ml，HCV RNA>1000copies/ml，HBsAg+ and anti-HCV+；
18. Has a known additional malignancy within the last 5 years, or that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer or patients with recurrent ovarian cancer has a known additional breast cancer that has been radical mastectomy and doesn't relapse within 3 years.
19. Patients with treatment history of SHR-1210 or any other PD-L1 or PD-1 antagonists or famitinib.
20. Patients who may receive live vaccine during the study, or previous had vaccination within 4 weeks.
21. Any other medical, psychiatric, or social condition deemed by the investigator to be likely to interfere with a subject's safety and participate in the study or would interfere with the interpretation of the results or lead to the trial being terminated early.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Quanren Wang, MD; (+86) 021-50118402; wangquanren@hrglobe.cn

• Listed Location Countries: China

Administrative Information

• NCT Number: NCT03827837
• Other Study ID Numbers: SHR-1210-II-213
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Jiangsu HengRui Medicine Co., Ltd.
• Original Responsible Party: Same as current
• Current Study Sponsor: Jiangsu HengRui Medicine Co., Ltd.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Dingwei Ye, MD; Fudan University
• Principal Investigator: Xiaohua Wu, MD; Fudan University

• PRS Account: Jiangsu HengRui Medicine Co., Ltd.
• Verification Date: June 2022