CompletedNCT03417895PASSIONUpdated Aug 7, 2024Results posted

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

A Phase 2 interventional study of SHR-1210 and Apatinib in Small-cell Lung Cancer, sponsored by Jiangsu HengRui Medicine Co., Ltd.. Completed at 2 sites in China. Open to participants aged 18 Years to 70 Years. Per ClinicalTrials.gov, last updated 2024-08-07.

Sponsored by Jiangsu HengRui Medicine Co., Ltd. · Phase 2, Interventional, and Treatment

Phase: Phase 2
Study type: Interventional
Enrollment: 59
Allocation: Randomized
Ages: 18 Years to 70 Years
Sex: All

Study 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.

Conditions studied

Small-cell Lung Cancer

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Who can participate

Ages eligible: 18 Years to 70 Years
Sexes eligible: All
Accepts healthy volunteers: No

Inclusion criteria

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

Exclusion criteria

Exclusion Criteria:

Histologically or cytologically confirmed mixed non-small cell and small cell carcinoma.
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.
Prior exposure to anti-VEGF or anti-VEGFR therapy.
Active brain metastasis or meningeal metastasis.
Clinically significant third space effusion (e.g., uncontrolled pericardial effusion, ascites or pleural effusion by extraction or other treatment).
Known hypersensitivity to study drug or any of its excipients; known hypersensitivity to any antibody.
Treatment with any other investigational agent or participation in another clinical trial within 4 weeks prior to screening.
Other conditions that the investigator thinks unsuitable in this study.

Study design

Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel assignment
Masking: None (open label)
Enrollment: 59 participants (actual)

Study arms

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

Interventions

DrugSHR-1210
A humanized anti-PD-1 monoclonal antibody
DrugApatinib
A tyrosine kinase inhibitor selectively targeting VEGFR-2

What researchers measure

Primary outcomes

Adverse Event
Evaluation of adverse event rate according to CTCAE v4.03
Time frame: 24 months
ORR
Objective response rate according to RECIST v1.1 (Response was assessed with CT or MRI using RECIST v1.1, Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to\<10 mm; Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Over all response：CR+PR)
Time frame: 6 months

Secondary outcomes

OS Rate
Overall survival rate
Time frame: 6 months
PFS
Progression-free survival according to RECIST v1.1
Time frame: Imaging assessment was performed on C1D28 and every 8 weeks after C1D28 until radiographic progressive disease (PD) was documented.
TTR
Time to response according to RECIST v1.1 (Response was assessed with CT or MRI using RECIST v1.1, Time to response (TTR): date of first dose to date of first documented CR or PR)
Time frame: Imaging assessment was performed on C1D28 and every 8 weeks after C1D28 until radiographic progressive disease (PD) was documented.
DoR
Duration of response according to RECIST v1.1 (Response was assessed with CT or MRI using RECIST v1.1, Duration of response (DoR): DoR will only be performed in subjects who have a confirmed tumor response (CR or PR) after treatment
Time frame: Imaging assessment was performed on C1D28 and every 8 weeks after C1D28 until radiographic progressive disease (PD) was documented.
DCR
Disease control rate according to RECIST v1.1 (Response was assessed with CT or MRI using RECIST v1.1; Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to\<10 mm; Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Stable Disease (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. Disease control rate (DCR): CR+PR+SD
Time frame: Imaging assessment was performed on C1D28 and every 8 weeks after C1D28 until radiographic progressive disease (PD) was documented.
OS
Overall survival
Time frame: on average of 2 years

Results

Posted Aug 7, 2024

Participant flow

Participant flow — Overall Study
Milestone	A(SHR-1210+Apatinib)	B(SHR-1210+Apatinib)	C(SHR-1210+Apatinib)
Started	47	6	6
Completed	47	6	6
Not completed	0	0	0

Outcome measures

PrimaryAdverse Event

Evaluation of adverse event rate according to CTCAE v4.03

Time frame:: 24 months
Reported as:: Number · participants

Adverse Event
participants	A(SHR-1210+Apatinib)	B(SHR-1210+Apatinib)	C(SHR-1210+Apatinib)
Adverse Event	47	6	5

PrimaryORR

Objective response rate according to RECIST v1.1 (Response was assessed with CT or MRI using RECIST v1.1, Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to\<10 mm; Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Over all response：CR+PR)

Time frame:: 6 months
Reported as:: Number · percentage of number of people in FAS

ORR
percentage of number of people in FAS	A(SHR-1210+Apatinib)	B(SHR-1210+Apatinib)	C(SHR-1210+Apatinib)
ORR	34.0 (20.9 to 49.3)	33.3 (4.3 to 77.7)	33.3 (4.3 to 77.7)

SecondaryOS Rate

Overall survival rate

Time frame:: 6 months
Reported as:: Number · percentage of number of people in FAS

OS Rate
percentage of number of people in FAS	A(SHR-1210+Apatinib)	B(SHR-1210+Apatinib)	C(SHR-1210+Apatinib)
OS Rate	63.8 (48.4 to 75.7)	66.7 (19.5 to 90.4)	44.4 (6.6 to 78.5)

SecondaryPFS

Progression-free survival according to RECIST v1.1

Time frame:: Imaging assessment was performed on C1D28 and every 8 weeks after C1D28 until radiographic progressive disease (PD) was documented.
Reported as:: Median · months

PFS
months	A(SHR-1210+Apatinib)	B(SHR-1210+Apatinib)	C(SHR-1210+Apatinib)
PFS	3.6 (1.9 to 4.6)	3.6 (2.7 to 8.3)	1.2 (0.9 to 19.7)

SecondaryTTR

Time to response according to RECIST v1.1 (Response was assessed with CT or MRI using RECIST v1.1, Time to response (TTR): date of first dose to date of first documented CR or PR)

Time frame:: Imaging assessment was performed on C1D28 and every 8 weeks after C1D28 until radiographic progressive disease (PD) was documented.
Reported as:: Median · months

TTR
months	A(SHR-1210+Apatinib)	B(SHR-1210+Apatinib)	C(SHR-1210+Apatinib)
TTR	1.0 (0.9 to 4.7)	1.8 (0.9 to 2.7)	4.6 (0.9 to 8.2)

SecondaryDoR

Duration of response according to RECIST v1.1 (Response was assessed with CT or MRI using RECIST v1.1, Duration of response (DoR): DoR will only be performed in subjects who have a confirmed tumor response (CR or PR) after treatment

Time frame:: Imaging assessment was performed on C1D28 and every 8 weeks after C1D28 until radiographic progressive disease (PD) was documented.
Reported as:: Median · months

DoR
months	A(SHR-1210+Apatinib)	B(SHR-1210+Apatinib)	C(SHR-1210+Apatinib)
DoR	6.2 (3.7 to 9.2)	4.2 (3.6 to 4.7)	8.0 (4.6 to 11.5)

SecondaryDCR

Disease control rate according to RECIST v1.1 (Response was assessed with CT or MRI using RECIST v1.1; Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to\<10 mm; Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Stable Disease (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. Disease control rate (DCR): CR+PR+SD

Time frame:: Imaging assessment was performed on C1D28 and every 8 weeks after C1D28 until radiographic progressive disease (PD) was documented.
Reported as:: Number · percentage of number of people in FAS

DCR
percentage of number of people in FAS	A(SHR-1210+Apatinib)	B(SHR-1210+Apatinib)	C(SHR-1210+Apatinib)
DCR	68.1 (52.9 to 80.9)	100.0 (54.1 to 100.0)	50.0 (11.8 to 88.2)

SecondaryOS

Overall survival

Time frame:: on average of 2 years
Reported as:: Median · months

OS
months	A(SHR-1210+Apatinib)	B(SHR-1210+Apatinib)	C(SHR-1210+Apatinib)
OS	8.8 (4.9 to 12.3)	11.2 (4.9 to NA)	5.4 (1.5 to NA)

Adverse events

Collected over 24 months. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
A(SHR-1210+Apatinib)	17/47 (36.2%)	27/47 (57.4%)	47/47 (100%)
B(SHR-1210+Apatinib)	1/6 (16.7%)	4/6 (66.7%)	6/6 (100%)
C(SHR-1210+Apatinib)	2/6 (33.3%)	2/6 (33.3%)	5/6 (83.3%)

Most frequent serious events

Showing 10 of 30

Most frequent serious events
Event	A(SHR-1210+Apatinib)	B(SHR-1210+Apatinib)	C(SHR-1210+Apatinib)
Aspartate aminotransferase increasedInvestigations	3/47	2/6	0/6
Alanine aminotransferase increasedInvestigations	2/47	2/6	0/6
HemoptysisRespiratory, thoracic and mediastinal disorders	1/47	2/6	0/6
DeathGeneral disorders	9/47	1/6	0/6
Progressive diseaseGeneral disorders	6/47	0/6	1/6
Platelet count decreasedInvestigations	4/47	1/6	0/6
Gamma-glutamyltransferase increasedInvestigations	0/47	1/6	0/6
Blood alkaline phosphatase increasedInvestigations	0/47	1/6	0/6
PneumoniaInfections and infestations	3/47	1/6	0/6
Respiratory tract infectionInfections and infestations	0/47	1/6	0/6

Most frequent other events

Showing 10 of 105

Most frequent other events
Event	A(SHR-1210+Apatinib)	B(SHR-1210+Apatinib)	C(SHR-1210+Apatinib)
HypertensionVascular disorders	28/47	6/6	3/6
Aspartate aminotransferase increasedInvestigations	28/47	4/6	5/6
AstheniaGeneral disorders	13/47	3/6	4/6
White blood cell count decreasedInvestigations	20/47	4/6	2/6
Neutrophil count decreasedInvestigations	14/47	4/6	2/6
Occult blood positiveInvestigations	4/47	4/6	0/6
VomitingGastrointestinal disorders	6/47	1/6	3/6
Alanine aminotransferase increasedInvestigations	22/47	2/6	3/6
Platelet count decreasedInvestigations	20/47	3/6	1/6
Blood creatinine increasedInvestigations	6/47	3/6	1/6

Baseline characteristics

Age, Continuous
Age, Continuous(years)	A(SHR-1210+Apatinib)	B(SHR-1210+Apatinib)	C(SHR-1210+Apatinib)	Total
Mean	60.3 ± 6.36	59.3 ± 7.39	54.2 ± 10.68	59.6 ± 7.08

Sex: Female, Male
Sex: Female, Male(Participants)	A(SHR-1210+Apatinib)	B(SHR-1210+Apatinib)	C(SHR-1210+Apatinib)	Total
Female	7	0	1	8
Male	40	6	5	51

Race (NIH/OMB)
Race (NIH/OMB)(Participants)	A(SHR-1210+Apatinib)	B(SHR-1210+Apatinib)	C(SHR-1210+Apatinib)	Total
American Indian or Alaska Native	0	0	0	0
Asian	47	6	6	59
Native Hawaiian or Other Pacific Islander	0	0	0	0
Black or African American	0	0	0	0
White	0	0	0	0
More than one race	0	0	0	0
Unknown or Not Reported	0	0	0	0

Region of Enrollment
Region of Enrollment(participants)	A(SHR-1210+Apatinib)	B(SHR-1210+Apatinib)	C(SHR-1210+Apatinib)	Total
China	47	6	6	59

Study locations

2 sites

Cancer Hospital Chinese Academy of Medical Science
Beijing, Beijing 100021, China
Zhejiang Cancer Hospital
Hangzhou, Zhejiang 310022, China

References and documents

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. PubMed 33166719 ↗

Study documents

Study protocol · Jun 12, 2018
Statistical analysis plan · Jul 27, 2020

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: Undecided

Registry details

Key details

Study ID: NCT03417895
Lead sponsor: Jiangsu HengRui Medicine Co., Ltd.
Responsible party: Sponsor
First posted: Jan 31, 2018
Start date: Apr 20, 2018
Primary completion: Aug 4, 2021
Completion: Aug 4, 2021
Results posted: Aug 7, 2024
Last update: Aug 7, 2024

Study contacts

Wei Shi

study director · Jiangsu Hengrui Pharmaceuticals Co.,Ltd

Oversight

Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No

View the source record on ClinicalTrials.gov ↗

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