Sintilimab in Combination With Gemcitabine and Platinum-Based Chemotherapy as First-Line Therapy for Advanced or Metastatic Squamous NSCLC

• Sponsor: Innovent Biologics (Suzhou) Co. Ltd. (Industry)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT03629925
• Collaborator: (none)
• Enrollment: 357
• Location: 1
• Arms: 2
• Anticipated Duration (Months): 38.1
• Patients Per Site Per Month: 9.4

Study Details

Study Description

Brief Summary

Efficacy and Safety Evaluation of IBI308 in Patients with Advanced or Recurrent Squamous NSCLC

Condition or Disease	Intervention/Treatment	Phase
Squamous NSCLC	Drug: Sintilimab; Drug: Gemcitabine; Drug: Cisplatin; Drug: Placebo; Drug: Carboplatin	Phase 3

Detailed Description

The anti-tumor activity of anti-PD-1 therapy in previously untreated Chinese squamous NSCLC patients will be investigated in this clinical trial.

Study Design

• Study Type: Interventional
• Actual Enrollment: 357 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-Blind, Phase III Study to Compare the Efficacy and Safety of Sintilimab (IBI308) in Combination With Gemcitabine and Platinum-Based Chemotherapy vs. Placebo in Combination With Gemcitabine and Platinum-Based Chemotherapy as First-Line Treatment for Patients With Advanced or Metastatic Squamous Non-Small-Cell Lung Cancer (NSCLC) (ORIENT-12)
• Actual Study Start Date: Sep 28, 2018
• Actual Primary Completion Date: Oct 15, 2019
• Anticipated Study Completion Date: Dec 1, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Sintilimab+ gemcitabine plus platinum Sintilimab combination arm: Sintilimab in combination with gemcitabine plus cisplatin or carboplatin	Drug: Sintilimab; 200mg, Q3W, day1, I.V.; consecutive cycles; Other Names: IBI308 ; Drug: Gemcitabine; 1000mg/m^2, Q3W, day 1and 8, I.V.; first 4 or 6 consecutive cycles.; Drug: Cisplatin; 75 mg/m^2, Q3W, day1, I.V.; first 4 or 6 consecutive cycles.; Drug: Carboplatin; AUC 5mg/ml/min, Q3W, day1, I.V.; first 4 or 6 consecutive cycles.
Placebo Comparator: Placebo+gemcitabine plus platinum Placebo combination arm: Placebo in combination with gemcitabine plus cisplatin or carboplatin	Drug: Gemcitabine; 1000mg/m^2, Q3W, day 1and 8, I.V.; first 4 or 6 consecutive cycles.; Drug: Cisplatin; 75 mg/m^2, Q3W, day1, I.V.; first 4 or 6 consecutive cycles.; Drug: Placebo; NA, Q3W, day1, I.V.; consecutive cycles; Drug: Carboplatin; AUC 5mg/ml/min, Q3W, day1, I.V.; first 4 or 6 consecutive cycles.

Outcome Measures

Primary Outcome Measures

1. PFS(Progression Free Survival) [Through Database Cutoff Date of 25 March 2020 (up to approximately 18 months)]

   PFS was defined as the time from randomization to the first documented PD or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. PFS according to RECIST 1.1 as assessed by BIRRC was reported for each arm.

Secondary Outcome Measures

1. OS (Overall Survival) [Through Database Cutoff Date of 15 October 2019 (up to approximately 13 months)]

   OS was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the final analysis were to be censored at the date of the last follow-up. OS was reported for each arm.

2. ORR(Objective Response Rate) [Through Database Cutoff Date of 25 March 2020 (up to approximately 18 months)]

   ORR was defined as the percentage of participants in the analysis population who had a confirmed Complete Response (CR: disappearance of all lesions) or Partial Response (PR: at least a 30% decrease in the sum of diameters [SOD] of target lesions, taking as reference the baseline SOD) according to RECIST 1.1. The percentage of participants who experienced a confirmed CR or PR according to RECIST 1.1 as assessed by BIRRC was reported as the ORR for each arm.

3. TTR (Time to Response) [Through Database Cutoff Date of 25 March 2020 (up to approximately 18 months)]

   TTR was defined as the time of participants from the first treatment administration to the first incidence of a confirmed CR (disappearance of all lesions) or PR (at least a 30% decrease in the sum of diameters [SOD] of target lesions, taking as reference the baseline SOD) according to RECIST 1.1. The time from first treatment administration to the first incidence of treatment response was reported as the TTR for each arm.

4. DCR (Disease Control Rate) [Through Database Cutoff Date of 25 March 2020 (up to approximately 18 months)]

   DCR was defined as the percentage of participants who had a CR (disappearance of all target lesions), PR (at least a 30% decrease in the sum of diameters of target lesions), or Stable Disease (SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease [PD: at least a 20% increase in the sum of diameters of target lesions and an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered PD]). The percentage of participants who experienced a confirmed CR, PR, or SD according to RECIST 1.1 as assessed by BIRRC was reported as the DCR for each arm.

5. DOR (Duration of Response) [Through Database Cutoff Date of 25 March 2020 (up to approximately 18 months)]

   For participants who demonstrated a confirmed CR (disappearance of all target lesions) or PR (At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, DOR was defined as the time from first documented evidence of a CR or PR until progressive disease (PD) or death. DOR for participants who had not progressed or died at the time of analysis was censored at the date of their last tumor assessment. Per RECIST 1.1, PD was defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered PD. DOR assessments were based on BIRRC assessment. The DOR according to RECIST 1.1 for all participants who experienced a confirmed CR or PR was reported for each arm.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Participants must sign written ICF prior tothe implementation of any procedures related to the study;

2. Aged ≥ 18 years and ≤ 75 years;

3. With a life expectancy of more than 3 months;

4. With at least one measurable lesion confirmed by the investigator according to RECIST v1.1.

Measurable lesions locatedin the field of previous radiotherapy or locoregional therapy canbe selected as target lesions if PD is confirmed;

1. Participants with histologically or cytologically confirmed locally advanced (stage IIIB/IIIC) who are ineligible for radical surgery or concurrent chemoradiotherapy, metastatic (stage IV)or recurrent squamous NSCLC based on the "8th Edition of the TNM Classification for LungCancer" issued by the International Association for the Study of Lung Cancer and the American Joint Committee on Cancer Classification;

2. With an ECOG PS score of 0 or 1;

3. Have not received any prior systemic anti-tumor therapy for advanced/metastatic disease; for participants who have received prior platinum-based adjuvant chemotherapy/radiotherapy,neoadjuvant chemotherapy/radiotherapy, or radical chemoradiotherapy, they are eligible for the study if PD occurs at > 6 months after the last treatment;

4. With adequate hematologic function, defined as ANC ≥ 1.5 × 10^{9/L, platelet count ≥ 100 × 10}9/L, and hemoglobin ≥ 90 g/L (noblood transfusion history within 7 days);

5. Adequate hepatic function, defined as TBIL ≤ 1.5 × ULN and AST as well as ALT ≤ 2.5 × ULN for all participants, or AST and ALT ≤ 5 × ULN for participants with liver metastasis;

6. Adequate renal function, defined as CCr ≥ 50 mL/min (Cockcroft-Gault formula);

7. Adequate coagulation function, defined as INR or PT ≤ 1.5 × ULN; for the participant who is receiving anticoagulant therapy, INR or PT within the proposed scope of the anticoagulantmedication is acceptable;

8. Female participants of childbearing age should be tested negative for urine or serum pregnancy within 3 days before the first dose of the study treatments. A blood pregnancy testis required if the urine pregnancy test is inconclusive;

9. For male and female participants with conception potential, highly effective contraception measures (failure rate < 1% per year) should be taken until at least 180 days afterdiscontinuation of the study treatment;

Note: Abstinence is acceptable as a method of contraception if it is the usual lifestyle and preferred method of contraception for the participant.

Exclusion Criteria:

1. Histological type of nonsquamousNSCLC. The dominant cell morphology must be identified for mixed cell type (participants with squamous cell carcinoma components > 50% can beenrolled); participants with small cell carcinoma, neuroendocrine carcinoma, and sarcoma components cannot be included;

2. Participants with known EGFR-sensitive mutations or ALK rearrangement;

3. Currently participating in an interventional clinical study, or treated with another study drug therapy or investigational device therapy within 4 weeks before the first dose;

4. Previously received the following therapies: anti-PD-1, anti-PD-L1, or anti-PD-L2 agents or agents targeting another stimulation or synergistically inhibiting TCR (e.g., CTLA-4, OX-40,and CD137);

5. Received proprietary Chinese medicines with anti-tumor indications or immunomodulators (thymosin, interferon, interleukin, etc.) within 2 weeks prior to the first dose, or received a major surgery within 3 weeks prior to the first dose;

6. With active hemoptysis, active diverticulitis, abdominal abscess, gastrointestinal obstruction, and peritoneal metastases requiring clinical intervention;

7. Have undergone solid organ transplantation or hematologic transplantation;

8. With clinically uncontrolled pleural effusion/ascites (participants who do not need effusion drainage or have no significant increase in effusion within 3 days after stopping drainage canbe enrolled);

9. With a tumor compressing the surrounding important organs (such as esophagus) with relevant symptoms, compressing the superior vena cava, or invading the mediastinal great vessels,heart, etc.;

10. With Class III-IV congestive cardiac failure (based on New York Heart Association Classification) or poorly controlled and clinically significant arrhythmia;

11. With any arterial thrombosis, embolism, or ischemia within 6 months prior to enrollment, such as myocardial infarction, unstable angina, cerebrovascular accident, and transient ischemicattack. With a history of deep venous thrombosis, pulmonary embolism, or any other seriousthromboembolic events within 3 months priorto enrollment (implantable port or catheter-related thrombosis, or superficial venous thrombosis is not considered as "serious"thromboembolism);

12. With known allergy to the active ingredients and/or any excipient of sintilimab , gemcitabine, cisplatin, orcarboplatin;

13. With active autoimmune disease requiring systemic treatment (e.g., use of disease-modifying drugs, corticosteroids, or immunosuppressive agents) within 2 years before the first dose.Replacement therapy (e.g., thyroxine, insulin, or physiologic doses of corticosteroids foradrenal or pituitary insufficiency) is not considered systemic;

14. Participants requiring long-term systemic use of corticosteroids. Participants requiring intermittent use of bronchodilators, inhaled corticosteroids, or localinjection ofcorticosteroids for COPD or asthma can be included in the study;

15. Full recovery (i.e., ≤ Grade 1 or reaching the baseline, excluding asthenia or alopecia) from toxicity and/or complications caused by any intervention has not achieved before thestart oftreatment;

16. Diagnosed with other malignant tumors within 5 years before the first dose, excluding radically cured cutaneous basal cell carcinoma, cutaneous squamous cell carcinoma, and/orradically resected carcinoma in situ. For other malignant tumors or lung cancer diagnosedmore than 5 years before the first dose, pathological or cytological diagnosis should beperformed for recurrent and metastatic lesions;

17. Symptomatic CNS metastasis. Participants with asymptomatic brain metastases or with stable symptoms after treatment of brain metastases are allowed to participate in this study as longas meeting all of the following criteria: presence of measurable lesions outside the CNS;absence of metastases in midbrain, pons, cerebellum, meninges, medulla oblongata, or spinalcord; maintain clinical stable condition for at least 2 weeks; discontinue hormone therapy 14 days prior to the first dose of the study treatments;

18. With a history of non-infectious pneumonia requiring corticosteroid therapy within 1year prior to the first dose or with non-infectious pneumonia at present;

19. With an active infection requiring treatment or have used systemic anti-infective drugs within one week prior to the first dose;

20. With known psychiatric disorder or substance abuse that could affect the compliance with study requirements;

21. Known history of HIV infection (i.e. HIV 1/2 antibody positive), known syphilis infection (syphilis antibody positive), or active tuberculosis;

22. With untreated active hepatitis B;

Note: Participants with hepatitis B who meet the following criteria are also eligible forinclusion:

HBV viral load must be less than 1000 copies/mL (200 IU/mL) or below LLD prior to thefirst dose, and participants should receive anti-HBV treatment to avoid virus reactivation throughout the therapeutic phase of the study; For participants with HBcAb (+), HBsAg (-), HBsAb (-), and HBV load (-), close monitoring is required instead of prophylactic anti-HBV treatment to avoid virus reactivation;

1. Participants with active HCV infection (HCV antibody positive and HCV-RNA level above the LLD);

2. Have received live vaccines within 30 days prior to the first dose; Note: Seasonal inactivated influenza virus vaccines for injection are allowed, while liveattenuated influenza vaccines forintranasal use are not acceptable;

3. With any medical history, disease, treatment, or laboratory abnormal finding that would interfere with the study results or prevent the participant from participating in the whole study,or the investigator believes that participation in this study is not in the best interest of theparticipant;

4. With local or systemic diseases not attributing to malignancy, or with cancer-related secondary diseases, which would result in a high medical risk and/or uncertainty in survivalevaluation

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Shanghai Pulmonary Hospital	Shanghai		China

Sponsors and Collaborators

• Innovent Biologics (Suzhou) Co. Ltd.

Investigators

• Principal Investigator: Caicun Zhou, Shanghai Pulmonary Hospital, Shanghai, China

Study Documents (Full-Text)

• Study Protocol - Nov 27, 2019
• Statistical Analysis Plan - Nov 17, 2020

More Information

Publications

None provided.

• Responsible Party: Innovent Biologics (Suzhou) Co. Ltd.
• ClinicalTrials.gov Identifier: NCT03629925
• Other Study ID Numbers: CIBI308C303
• First Posted: Aug 14, 2018
• Last Update Posted: Apr 1, 2021
• Last Verified: Mar 1, 2021

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Carcinoma, Non-Small-Cell Lung; Gemcitabine; Carboplatin

Study Results

Participant Flow

Recruitment Details	primary analysis data cutoff date: 15 October 2019; updated analysis data cutoff date: 25 March 2020

Arm/Group Title	Sintilimab+ Gemcitabine Plus Platinum	Placebo+Gemcitabine Plus Platinum
Arm/Group Description	Sintilimab 200mg IV, Gemcitabine 1.0 g/m^2 IV and Cisplatin 75 mg/m^2 or Carboplatin AUC 5 mg/ml/min IV Q3W.	Placebo IV, Gemcitabine 1.0 g/m^2 IV and Cisplatin 75 mg/m^2 or Carboplatin AUC 5 mg/ml/min IV Q3W.
Period Title: Overall Study
STARTED	179	178
COMPLETED	0	0
NOT COMPLETED	179	178

Baseline Characteristics

Arm/Group Title	Sintilimab+ Gemcitabine Plus Platinum	Placebo+Gemcitabine Plus Platinum	Total
Arm/Group Description	Sintilimab 200mg IV, Gemcitabine 1.0 g/m^2 IV and Cisplatin 75 mg/m^2 or Carboplatin AUC 5 mg/ml/min IV Q3W.	Placebo IV, Gemcitabine 1.0 g/m^2 IV and Cisplatin 75 mg/m^2 or Carboplatin AUC 5 mg/ml/min IV Q3W.	Total of all reporting groups
Overall Participants	179	178	357
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	61.9 (7.47)	61.0 (7.85)	61.5 (7.66)
Sex: Female, Male (Count of Participants)
Female	16 8.9%	14 7.9%	30 8.4%
Male	163 91.1%	164 92.1%	327 91.6%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%
Not Hispanic or Latino	179 100%	178 100%	357 100%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	179 100%	178 100%	357 100%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	0 0%	0 0%	0 0%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (Count of Participants)
China	179 100%	178 100%	357 100%

Outcome Measures

1. Primary Outcome

Title	PFS(Progression Free Survival)
Description	PFS was defined as the time from randomization to the first documented PD or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. PFS according to RECIST 1.1 as assessed by BIRRC was reported for each arm.
Time Frame	Through Database Cutoff Date of 25 March 2020 (up to approximately 18 months)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Sintilimab+ Gemcitabine Plus Platinum	Placebo+Gemcitabine Plus Platinum
Arm/Group Description	Sintilimab 200mg IV, Gemcitabine 1.0 g/m^2 IV and Cisplatin 75 mg/m^2 or Carboplatin AUC 5 mg/ml/min IV Q3W.	Placebo IV, Gemcitabine 1.0 g/m^2 IV and Cisplatin 75 mg/m^2 or Carboplatin AUC 5 mg/ml/min IV Q3W.
Measure Participants	179	178
Median (95% Confidence Interval) [months]	5.5	4.9

2. Secondary Outcome

Title	OS (Overall Survival)
Description	OS was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the final analysis were to be censored at the date of the last follow-up. OS was reported for each arm.
Time Frame	Through Database Cutoff Date of 15 October 2019 (up to approximately 13 months)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Sintilimab+ Gemcitabine Plus Platinum	Placebo+Gemcitabine Plus Platinum
Arm/Group Description	Sintilimab 200mg IV, Gemcitabine 1.0 g/m^2 IV and Cisplatin 75 mg/m^2 or Carboplatin AUC 5 mg/ml/min IV Q3W.	Placebo IV, Gemcitabine 1.0 g/m^2 IV and Cisplatin 75 mg/m^2 or Carboplatin AUC 5 mg/ml/min IV Q3W.
Measure Participants	179	178
Median (95% Confidence Interval) [Months]	NA	NA

3. Secondary Outcome

Title	ORR(Objective Response Rate)
Description	ORR was defined as the percentage of participants in the analysis population who had a confirmed Complete Response (CR: disappearance of all lesions) or Partial Response (PR: at least a 30% decrease in the sum of diameters [SOD] of target lesions, taking as reference the baseline SOD) according to RECIST 1.1. The percentage of participants who experienced a confirmed CR or PR according to RECIST 1.1 as assessed by BIRRC was reported as the ORR for each arm.
Time Frame	Through Database Cutoff Date of 25 March 2020 (up to approximately 18 months)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Sintilimab+ Gemcitabine Plus Platinum	Placebo+Gemcitabine Plus Platinum
Arm/Group Description	Sintilimab 200mg IV, Gemcitabine 1.0 g/m^2 IV and Cisplatin 75 mg/m^2 or Carboplatin AUC 5 mg/ml/min IV Q3W.	Placebo IV, Gemcitabine 1.0 g/m^2 IV and Cisplatin 75 mg/m^2 or Carboplatin AUC 5 mg/ml/min IV Q3W.
Measure Participants	179	178
Number (95% Confidence Interval) [Percentage of Participants]	44.7 25%	35.4 19.9%

4. Secondary Outcome

Title	TTR (Time to Response)
Description	TTR was defined as the time of participants from the first treatment administration to the first incidence of a confirmed CR (disappearance of all lesions) or PR (at least a 30% decrease in the sum of diameters [SOD] of target lesions, taking as reference the baseline SOD) according to RECIST 1.1. The time from first treatment administration to the first incidence of treatment response was reported as the TTR for each arm.
Time Frame	Through Database Cutoff Date of 25 March 2020 (up to approximately 18 months)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Sintilimab+ Gemcitabine Plus Platinum	Placebo+Gemcitabine Plus Platinum
Arm/Group Description	Sintilimab 200mg IV, Gemcitabine 1.0 g/m^2 IV and Cisplatin 75 mg/m^2 or Carboplatin AUC 5 mg/ml/min IV Q3W.	Placebo IV, Gemcitabine 1.0 g/m^2 IV and Cisplatin 75 mg/m^2 or Carboplatin AUC 5 mg/ml/min IV Q3W.
Measure Participants	80	63
Median (Full Range) [Months]	1.41	1.41

5. Secondary Outcome

Title	DCR (Disease Control Rate)
Description	DCR was defined as the percentage of participants who had a CR (disappearance of all target lesions), PR (at least a 30% decrease in the sum of diameters of target lesions), or Stable Disease (SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease [PD: at least a 20% increase in the sum of diameters of target lesions and an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered PD]). The percentage of participants who experienced a confirmed CR, PR, or SD according to RECIST 1.1 as assessed by BIRRC was reported as the DCR for each arm.
Time Frame	Through Database Cutoff Date of 25 March 2020 (up to approximately 18 months)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Sintilimab+ Gemcitabine Plus Platinum	Placebo+Gemcitabine Plus Platinum
Arm/Group Description	Sintilimab 200mg IV, Gemcitabine 1.0 g/m^2 IV and Cisplatin 75 mg/m^2 or Carboplatin AUC 5 mg/ml/min IV Q3W.	Placebo IV, Gemcitabine 1.0 g/m^2 IV and Cisplatin 75 mg/m^2 or Carboplatin AUC 5 mg/ml/min IV Q3W.
Measure Participants	179	178
Number (95% Confidence Interval) [Percentage of Participants]	86.0 48%	80.3 45.1%

6. Secondary Outcome

Title	DOR (Duration of Response)
Description	For participants who demonstrated a confirmed CR (disappearance of all target lesions) or PR (At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, DOR was defined as the time from first documented evidence of a CR or PR until progressive disease (PD) or death. DOR for participants who had not progressed or died at the time of analysis was censored at the date of their last tumor assessment. Per RECIST 1.1, PD was defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered PD. DOR assessments were based on BIRRC assessment. The DOR according to RECIST 1.1 for all participants who experienced a confirmed CR or PR was reported for each arm.
Time Frame	Through Database Cutoff Date of 25 March 2020 (up to approximately 18 months)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Sintilimab+ Gemcitabine Plus Platinum	Placebo+Gemcitabine Plus Platinum
Arm/Group Description	Sintilimab 200mg IV, Gemcitabine 1.0 g/m^2 IV and Cisplatin 75 mg/m^2 or Carboplatin AUC 5 mg/ml/min IV Q3W.	Placebo IV, Gemcitabine 1.0 g/m^2 IV and Cisplatin 75 mg/m^2 or Carboplatin AUC 5 mg/ml/min IV Q3W.
Measure Participants	80	63
Median (95% Confidence Interval) [Months]	6.05	5.06

Adverse Events

Time Frame	Through database cutoff date of 25 March 2020 (up to approximately 18 months)
Adverse Event Reporting Description	All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.
Arm/Group Title	Sintilimab+ Gemcitabine Plus Platinum		Placebo+Gemcitabine Plus Platinum
Arm/Group Description	Sintilimab 200mg IV, Gemcitabine 1.0 g/m^2 IV and Cisplatin 75 mg/m^2 or Carboplatin AUC 5 mg/ml/min IV Q3W.		Placebo IV, Gemcitabine 1.0 g/m^2 IV and Cisplatin 75 mg/m^2 or Carboplatin AUC 5 mg/ml/min IV Q3W.
All Cause Mortality
	Sintilimab+ Gemcitabine Plus Platinum		Placebo+Gemcitabine Plus Platinum
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	65/179 (36.3%)		71/178 (39.9%)
Serious Adverse Events
	Sintilimab+ Gemcitabine Plus Platinum		Placebo+Gemcitabine Plus Platinum
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	90/179 (50.3%)		80/178 (44.9%)
Blood and lymphatic system disorders
Anaemia	6/179 (3.4%)		6/178 (3.4%)
Bone marrow failure	3/179 (1.7%)		0/178 (0%)
Thrombocytopenia	2/179 (1.1%)		2/178 (1.1%)
Febrile neutropenia	1/179 (0.6%)		2/178 (1.1%)
Leukopenia	1/179 (0.6%)		0/178 (0%)
Agranulocytosis	0/179 (0%)		1/178 (0.6%)
Cardiac disorders
Acute myocardial infarction	1/179 (0.6%)		0/178 (0%)
Myocarditis	1/179 (0.6%)		1/178 (0.6%)
Supraventricular tachycardia	1/179 (0.6%)		0/178 (0%)
Acute coronary syndrome	0/179 (0%)		1/178 (0.6%)
Arrhythmia	0/179 (0%)		1/178 (0.6%)
Cardiac arrest	0/179 (0%)		1/178 (0.6%)
Myocardial infarction	0/179 (0%)		1/178 (0.6%)
Pericardial effusion	0/179 (0%)		1/178 (0.6%)
Tachycardia	0/179 (0%)		1/178 (0.6%)
Ventricular arrhythmia	0/179 (0%)		1/178 (0.6%)
Ventricular extrasystoles	0/179 (0%)		1/178 (0.6%)
Ventricular tachycardia	0/179 (0%)		1/178 (0.6%)
Endocrine disorders
Immune-mediated endocrinopathy	1/179 (0.6%)		0/178 (0%)
Hypophysitis	0/179 (0%)		1/178 (0.6%)
Gastrointestinal disorders
Colitis ulcerative	1/179 (0.6%)		0/178 (0%)
Immune-mediated enterocolitis	1/179 (0.6%)		0/178 (0%)
Upper gastrointestinal haemorrhage	1/179 (0.6%)		0/178 (0%)
Vomiting	1/179 (0.6%)		2/178 (1.1%)
Constipation	0/179 (0%)		1/178 (0.6%)
Diarrhoea	0/179 (0%)		1/178 (0.6%)
Dysphagia	0/179 (0%)		1/178 (0.6%)
Gastrointestinal perforation	0/179 (0%)		1/178 (0.6%)
General disorders
Pyrexia	5/179 (2.8%)		3/178 (1.7%)
Asthenia	2/179 (1.1%)		0/178 (0%)
Death	2/179 (1.1%)		5/178 (2.8%)
Sudden death	0/179 (0%)		2/178 (1.1%)
Hepatobiliary disorders
Hepatic function abnormal	2/179 (1.1%)		0/178 (0%)
Drug-induced liver injury	0/179 (0%)		2/178 (1.1%)
Infections and infestations
Pneumonia	22/179 (12.3%)		14/178 (7.9%)
Enteritis infectious	2/179 (1.1%)		0/178 (0%)
Sepsis	2/179 (1.1%)		0/178 (0%)
Encephalitis	1/179 (0.6%)		0/178 (0%)
Pneumonia bacterial	0/179 (0%)		1/178 (0.6%)
Injury, poisoning and procedural complications
Foreign body in gastrointestinal tract	0/179 (0%)		1/178 (0.6%)
Road traffic accident	0/179 (0%)		1/178 (0.6%)
Toxicity to various agents	0/179 (0%)		1/178 (0.6%)
Investigations
Platelet count decreased	32/179 (17.9%)		32/178 (18%)
White blood cell count decreased	7/179 (3.9%)		8/178 (4.5%)
Neutrophil count decreased	5/179 (2.8%)		5/178 (2.8%)
Amylase increased	3/179 (1.7%)		0/178 (0%)
Lipase increased	2/179 (1.1%)		0/178 (0%)
Alanine aminotransferase increased	1/179 (0.6%)		0/178 (0%)
Aspartate aminotransferase increased	1/179 (0.6%)		0/178 (0%)
Blood thyroid stimulating hormone decreased	1/179 (0.6%)		0/178 (0%)
Platelet count increased	1/179 (0.6%)		0/178 (0%)
Blood creatine phosphokinase increased	0/179 (0%)		1/178 (0.6%)
Blood creatinine increased	0/179 (0%)		1/178 (0.6%)
Metabolism and nutrition disorders
Hyponatraemia	2/179 (1.1%)		3/178 (1.7%)
Hypoalbuminaemia	1/179 (0.6%)		2/178 (1.1%)
Hypochloraemia	1/179 (0.6%)		0/178 (0%)
Hypophagia	1/179 (0.6%)		1/178 (0.6%)
Hypoproteinaemia	1/179 (0.6%)		0/178 (0%)
Hypercalcaemia	0/179 (0%)		1/178 (0.6%)
Hyperkalaemia	0/179 (0%)		1/178 (0.6%)
Hypokalaemia	0/179 (0%)		1/178 (0.6%)
Type 2 diabetes mellitus	0/179 (0%)		1/178 (0.6%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/179 (0.6%)		0/178 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer pain	1/179 (0.6%)		0/178 (0%)
Metastases to bone	1/179 (0.6%)		0/178 (0%)
Metastases to central nervous system	0/179 (0%)		1/178 (0.6%)
Nervous system disorders
Altered state of consciousness	1/179 (0.6%)		0/178 (0%)
Cerebral infarction	1/179 (0.6%)		2/178 (1.1%)
Cerebrovascular accident	0/179 (0%)		1/178 (0.6%)
Speech disorder	0/179 (0%)		1/178 (0.6%)
Syncope	0/179 (0%)		1/178 (0.6%)
Renal and urinary disorders
Proteinuria	0/179 (0%)		1/178 (0.6%)
Respiratory, thoracic and mediastinal disorders
Haemoptysis	8/179 (4.5%)		4/178 (2.2%)
Pneumonitis	4/179 (2.2%)		1/178 (0.6%)
Immune-mediated pneumonitis	3/179 (1.7%)		0/178 (0%)
Asphyxia	1/179 (0.6%)		0/178 (0%)
Cough	1/179 (0.6%)		1/178 (0.6%)
Interstitial lung disease	1/179 (0.6%)		0/178 (0%)
Pleural effusion	1/179 (0.6%)		0/178 (0%)
Pulmonary artery thrombosis	1/179 (0.6%)		0/178 (0%)
Pulmonary haemorrhage	1/179 (0.6%)		0/178 (0%)
Bronchostenosis	0/179 (0%)		1/178 (0.6%)
Hiccups	0/179 (0%)		1/178 (0.6%)
Pneumothorax	0/179 (0%)		1/178 (0.6%)
Pulmonary embolism	0/179 (0%)		1/178 (0.6%)
Respiratory failure	0/179 (0%)		1/178 (0.6%)
Skin and subcutaneous tissue disorders
Rash	5/179 (2.8%)		0/178 (0%)
Erythema	1/179 (0.6%)		0/178 (0%)
Subcutaneous emphysema	0/179 (0%)		1/178 (0.6%)
Vascular disorders
Venous thrombosis	1/179 (0.6%)		0/178 (0%)
Other (Not Including Serious) Adverse Events
	Sintilimab+ Gemcitabine Plus Platinum		Placebo+Gemcitabine Plus Platinum
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	179/179 (100%)		178/178 (100%)
Blood and lymphatic system disorders
Anaemia	167/179 (93.3%)		161/178 (90.4%)
Cardiac disorders
Ventricular extrasystoles	10/179 (5.6%)		3/178 (1.7%)
Sinus tachycardia	9/179 (5%)		6/178 (3.4%)
Supraventricular extrasystoles	9/179 (5%)		3/178 (1.7%)
Endocrine disorders
Hypothyroidism	23/179 (12.8%)		9/178 (5.1%)
Hyperthyroidism	10/179 (5.6%)		6/178 (3.4%)
Gastrointestinal disorders
Nausea	71/179 (39.7%)		73/178 (41%)
Vomiting	58/179 (32.4%)		61/178 (34.3%)
Constipation	55/179 (30.7%)		45/178 (25.3%)
Diarrhoea	25/179 (14%)		19/178 (10.7%)
Abdominal distension	14/179 (7.8%)		16/178 (9%)
General disorders
Asthenia	60/179 (33.5%)		60/178 (33.7%)
Pyrexia	52/179 (29.1%)		47/178 (26.4%)
Chest discomfort	13/179 (7.3%)		10/178 (5.6%)
Oedema peripheral	9/179 (5%)		3/178 (1.7%)
Hepatobiliary disorders
Hepatic function abnormal	16/179 (8.9%)		8/178 (4.5%)
Infections and infestations
Pneumonia	40/179 (22.3%)		28/178 (15.7%)
Upper respiratory tract infection	13/179 (7.3%)		11/178 (6.2%)
Urinary tract infection	13/179 (7.3%)		8/178 (4.5%)
Investigations
White blood cell count decreased	159/179 (88.8%)		153/178 (86%)
Neutrophil count decreased	149/179 (83.2%)		146/178 (82%)
Platelet count decreased	130/179 (72.6%)		125/178 (70.2%)
Aspartate aminotransferase increased	43/179 (24%)		35/178 (19.7%)
Alanine aminotransferase increased	42/179 (23.5%)		44/178 (24.7%)
Weight decreased	35/179 (19.6%)		24/178 (13.5%)
Lymphocyte count decreased	17/179 (9.5%)		14/178 (7.9%)
Blood creatinine increased	16/179 (8.9%)		13/178 (7.3%)
Amylase increased	14/179 (7.8%)		6/178 (3.4%)
Blood albumin decreased	12/179 (6.7%)		7/178 (3.9%)
Blood glucose increased	11/179 (6.1%)		14/178 (7.9%)
Gamma-glutamyltransferase increased	10/179 (5.6%)		12/178 (6.7%)
Weight increased	10/179 (5.6%)		9/178 (5.1%)
Blood bilirubin increased	9/179 (5%)		11/178 (6.2%)
Metabolism and nutrition disorders
Decreased appetite	57/179 (31.8%)		53/178 (29.8%)
Hypophagia	28/179 (15.6%)		15/178 (8.4%)
Hypokalaemia	26/179 (14.5%)		17/178 (9.6%)
Hyponatraemia	26/179 (14.5%)		33/178 (18.5%)
Hypoalbuminaemia	25/179 (14%)		21/178 (11.8%)
Hypoproteinaemia	22/179 (12.3%)		15/178 (8.4%)
Hypocalcaemia	11/179 (6.1%)		7/178 (3.9%)
Hypochloraemia	9/179 (5%)		13/178 (7.3%)
Hyperglycaemia	8/179 (4.5%)		13/178 (7.3%)
Musculoskeletal and connective tissue disorders
Back pain	14/179 (7.8%)		21/178 (11.8%)
Nervous system disorders
Dizziness	11/179 (6.1%)		9/178 (5.1%)
Headache	10/179 (5.6%)		7/178 (3.9%)
Psychiatric disorders
Insomnia	15/179 (8.4%)		16/178 (9%)
Renal and urinary disorders
Proteinuria	21/179 (11.7%)		15/178 (8.4%)
Respiratory, thoracic and mediastinal disorders
Haemoptysis	27/179 (15.1%)		22/178 (12.4%)
Cough	17/179 (9.5%)		19/178 (10.7%)
Productive cough	9/179 (5%)		9/178 (5.1%)
Dyspnoea	6/179 (3.4%)		12/178 (6.7%)
Hiccups	6/179 (3.4%)		9/178 (5.1%)
Skin and subcutaneous tissue disorders
Rash	42/179 (23.5%)		26/178 (14.6%)
Pruritus	22/179 (12.3%)		10/178 (5.6%)
Alopecia	9/179 (5%)		10/178 (5.6%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.