SHR-1210 Combined With Apatinib in Treatment of ED-SCLC After Failure of First Line Standard Therapy (PASSION)

• ClinicalTrials.gov Identifier: NCT03417895
• Recruitment Status: Completed
• First Posted: January 31, 2018
• Last Update Posted: February 3, 2023
• Sponsor: Jiangsu HengRui Medicine Co., Ltd.
• Information provided by (Responsible Party): Jiangsu HengRui Medicine Co., Ltd.

Tracking Information

• First Submitted Date: January 8, 2018
• First Posted Date: January 31, 2018
• Last Update Posted Date: February 3, 2023
• Actual Study Start Date: April 20, 2018
• Actual Primary Completion Date: August 4, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 29, 2018)

• Adverse event of part 1 [ Time Frame: on average of of 3 months(First 6 subjects in each arm) ]
  • Evaluation of adverse event rate according to CTCAE v4.03
• ORR [ Time Frame: 6 months ]
  • Objective response rate according to RECIST v1.1

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: January 29, 2018)

• Adverse event [ Time Frame: 6 months ]
  • Evaluation of adverse event rate according to CTCAE v4.03
• OS rate [ Time Frame: 6 months ]
  • OS rate
• PFS [ Time Frame: 6 months ]
  • Progression-free survival according to RECIST v1.1
• TTR [ Time Frame: 6 months ]
  • Time to response according to RECIST v1.1
• DoR [ Time Frame: 6 months ]
  • Duration of response according to RECIST v1.1
• DCR [ Time Frame: 6 months ]
  • Disease control rate according to RECIST v1.1
• OS [ Time Frame: on average of 2 years ]
  • Overall survival
• Immunogenicity [ Time Frame: 6 months ]
  • Positive rate of anti-drug antibody and neutralizing antibody

• 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: SHR-1210 Combined With Apatinib in Treatment of ED-SCLC After Failure of First Line Standard Therapy
• Official Title: Anti-PD-1 Antibody SHR-1210 Combined With Anti-angiogenesis Inhibitor Apatinib in Treatment of Extensive-stage Disease Small Cell Lung Cancer After Failure of First Line Standard Therapy

Brief Summary

This is a multi-center, open-label, phase II study of intravenous (IV) SHR-1210 at 200mg,q2w in combination with Apatinib at one dose (375mg). Comparison of 3 different dose schedules in subjects with extensive-stage disease small cell lung cancer. SHR-1210 is a humanized monoclonal antibody against Programmed death 1(PD-1). Apatinib is a new kind of selective Vascular Endothelial Growth Factor Receptor 2(VEGFR-2) tyrosine kinase inhibitor (TKI).

The study is composed of two parts. Part 1 of the study will determine the safety and tolerability of SHR-1210 in combination with Apatinib in first 6 subjects of each arm. The second phase of treatment was carried out by selecting one group of administration mode and the tolerated dose of Apatinib. Part 2 of the study will determine the safety and efficacy of SHR-1210 in combination with Apatinib in 39 subjects.

Detailed Description

Subjects will be 1:1:1 randomly assigned to receive

• SHR-1210 200mg, IV, Q2W and Apatinib 375mg, PO, QD, or
• SHR-1210 200mg, IV, Q2W and Apatinib 375mg, PO, QD（5 Days on, 2 Days off）, or
• SHR-1210 200mg, IV, Q2W and Apatinib 375mg, PO, QD（7 Days on, 7 Days off） treatment until disease progression, unacceptable toxicity, or death.

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Small-cell Lung Cancer

Intervention

• Drug: SHR-1210
  A humanized anti-PD-1 monoclonal antibody
• Drug: Apatinib
  A tyrosine kinase inhibitor selectively targeting VEGFR-2

Study Arms

• Experimental: A(SHR-1210+Apatinib)
  • SHR-1210 200mg, IV, Q2W and Apatinib 375mg, PO, QD
  Interventions:

  • Drug: SHR-1210
  • Drug: Apatinib
• Experimental: B(SHR-1210+Apatinib)
  • SHR-1210 200mg, IV, Q2W and Apatinib 375mg, PO, QD（5 Days on, 2 Days off）
  Interventions:

  • Drug: SHR-1210
  • Drug: Apatinib
• Experimental: C(SHR-1210+Apatinib)
  • SHR-1210 200mg, IV, Q2W and Apatinib 375mg, PO, QD（7 Days on, 7 Days off）
  Interventions:

  • Drug: SHR-1210
  • Drug: Apatinib

• Publications *: Fan Y, Zhao J, Wang Q, Huang D, Li X, Chen J, Fang Y, Duan J, Zhou C, Hu Y, Yang H, Hu Y, Zhou J, Lin X, Wang L, Wang Z, Xu Y, Zhang T, Shi W, Zou J, Wang J. Camrelizumab Plus Apatinib in Extensive-Stage SCLC (PASSION): A Multicenter, Two-Stage, Phase 2 Trial. J Thorac Oncol. 2021 Feb;16(2):299-309. doi: 10.1016/j.jtho.2020.10.002. Epub 2020 Nov 6.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: July 1, 2022): 59
• Original Estimated Enrollment (submitted: January 29, 2018): 135
• Actual Study Completion Date: August 4, 2021
• Actual Primary Completion Date: August 4, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Signed inform consent form
2. Age >= 18 years and <= 70 years
3. Histologically or cytologically confirmed small cell lung cancer
4. ED-SCLC according to Veterans Administration Lung Study Group
5. Radiographically progression following a platinum-based standard prior chemotherapy regimen.
6. Eastern Cooperative Oncology Group performance status of 0 or 1
7. Measurable disease as defined by RECIST v1.1
8. Life expectancy >= 8 weeks
9. Adequate hematologic and end organ function

Exclusion Criteria:

1. Histologically or cytologically confirmed mixed non-small cell and small cell carcinoma
2. Prior exposure to therapeutic anticancer vaccines; prior exposure to any T cell co-stimulatory therapy or immune checkpoint inhibitors, including but not limited to other anti-CTLA-4, anti-PD-1, anti-PD-L1 and anti-PD-L2 antibodies
3. Prior exposure to anti-VEGF or anti-VEGFR therapy
4. Active brain metastasis or meningeal metastasis.
5. Clinically significant third space effusion (e.g., uncontrolled pericardial effusion, ascites or pleural effusion by extraction or other treatment)
6. Known hypersensitivity to study drug or any of its excipients; known hypersensitivity to any antibody
7. Treatment with any other investigational agent or participation in another clinical trial within 4 weeks prior to screening
8. Other conditions that the investigator thinks unsuitable in this study

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 70 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: China

Administrative Information

• NCT Number: NCT03417895
• Other Study ID Numbers: SHR-1210-II-206
• Has Data Monitoring Committee: No

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

• Plan to Share IPD: Undecided

• 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

• Study Director: Wei Shi; Jiangsu Hengrui Pharmaceuticals Co.,Ltd

• PRS Account: Jiangsu HengRui Medicine Co., Ltd.
• Verification Date: February 2023