Overview

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

Status:
Active, not recruiting
Trial end date:
2021-12-01
Target enrollment:
0
Participant gender:
All
Summary
Efficacy and Safety Evaluation of IBI308 in Patients with Advanced or Recurrent Squamous NSCLC
Phase:
Phase 3
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
Innovent Biologics (Suzhou) Co. Ltd.
Treatments:
Carboplatin
Gemcitabine
Criteria
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;

5. 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;

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

7. 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;

8. 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);

9. 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;

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

11. 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;

12. 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;

13. 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;

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

24. 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;

25. 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;

26. 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