Sintilimab ± IBI305 Plus Chemotherapy (Pemetrexed + Cisplatin) for EGFRm + Locally Advanced or Metastasis Non-Squamous NSCLC Patients After EGFR-TKI Treatment Failure

Innovent Biologics

Status and phase: Completed; Phase 3

Conditions: Non-Squamous Non-Small Cell Lung Cancer

Treatments: Drug: Placebo2; Drug: Cisplatin; Drug: IBI305; Drug: Pemetrexed; Drug: Sintilimab; Drug: Placebo1

Study type: Interventional

Funder types: Industry

Identifiers

NCT03802240

CIBI338A301

Details and patient eligibility

About

The anti-tumor activity of anti-PD-1 therapy and VEGF inhibitor in TKI-resistant EGFR-mutated non-squamous NSCLC Chinese patients will be investigated in this clinical trial.

Enrollment: 492 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Main Inclusion Criteria:

1. Signed written informed consent before any trial-related processes;
2. Age ≥ 18 years and <75 years male or females;
3. Has a histologically or cytologically confirmed stage IIIB/IIIC (American Joint Committee on Cancer [AJCC] 8th edition) NSCLC that is unresectable and not fit for radical concurrent chemoradiotherapy, or metastatic / recurrent non-squamous NSCLC;
4. Patients with EGFR mutation confirmed by tumor histology or cytology or hematology prior to EGFR-TKI treatment
5. EGFR-TKI resistance, confirmed by RECIST 1.1
6. The investigator confirms at least one measurable lesion according to RECIST 1.1. A measurable lesion located in the field of previous radiation therapy or after local treatment may be selected as a target lesion if progression is confirmed; The Eastern Cancer Cooperative Group (ECOG) performance score of 0 or 1;

Exclusion criteria:

1. Squamous cell > 10%. If small cell types are present, the subject is not eligible for inclusion.;

2. Has previously received systemic anti-tumor treatment other than EGFR-TKI for or advanced non-squamous NSCLC (including cytotoxic chemotherapy for radiotherapy, do not include other systemic treatment for other cured tumors);

3. Has previously received the following therapies: anti-PD-1, anti-PD-L1 or anti-PD-L2 drugs or any other stimulatory or inhibitory agents of T cell receptors (eg CTLA-4, OX-40, CD137);

4. Has received EGFR-TKI treatment within 2 weeks;

5. Diagnosed of immunodeficiency or has received systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drugs.

6. History of pneumonitis requiring steroid therapy or the presence of interstitial lung disease within 1 year prior to the first dose of study drugs;

7. Symptomatic central nervous system metastases (CNS) metastasis and/or cancerous meningitis.

   Hemoptysis within 3 months,

8. Full-dose oral or parenteral anticoagulant or thrombolytic agent for 10 consecutive days within 2 weeks. prophylactic use of anticoagulants is allowed;

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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492 participants in 3 patient groups

Sintilimab +IBI305+Pemetrexed+Cisplatin

Experimental group

Description:

Drug: Sintilimab 200mg IV Q3W Other Name: IBI308 Drug: IBI305 15mg/kg IV Q3W Drug: Pemetrexed 500mg/m2 IV Q3W Drug: Cisplatin 75mg/m2 IV Q3W

Treatment:

Drug: Sintilimab

Drug: IBI305

Drug: Cisplatin

Drug: Pemetrexed

Sintilimab +Placebo2+Pemetrexed+Cisplatin

Experimental group

Description:

Drug: Sintilimab 200mg IV Q3W Other Name: IBI308 Drug: Pemetrexed 500mg/m2 IV Q3W Drug: Cisplatin 75mg/m2 IV Q3W Drug: Placebo2 Placebo2 IV Q3W

Treatment:

Drug: Sintilimab

Drug: Placebo2

Drug: Cisplatin

Drug: Pemetrexed

Placebo1+Placebo2+Pemetrexed+Cisplatin

Active Comparator group

Description:

Drug: Pemetrexed 500mg/m2 IV Q3W Drug: Cisplatin 75mg/m2 IV Q3W Drug: Placebo1 Placebo1 IV Q3W Drug: Placebo2 Placebo2 IV Q3W

Treatment:

Drug: Placebo1

Drug: Placebo2

Drug: Cisplatin

Drug: Pemetrexed