A Study of IBI110 in Combination With Sintilimab and Chemotherapy in Patients With Untreated Extensive-Stage Small Cell Lung Cancer

Phase 1

Completed

• Conditions: SCLC
• Interventions: Drug: Carboplatin; Drug: Cisplatin; Drug: Etoposide; Drug: Sintilimab; Drug: IBI110

• Registration Number: NCT05026593
• Lead Sponsor: Innovent Biologics (Suzhou) Co. Ltd.

Brief Summary

IBI110 is an investigational drug under evaluation for treatment of small cell lung cancer. The purpose of the study was to assess the Efficacy and Safety of IBI110 in combination with Sintilimab and chemotherapy with untreated ES-SCLC.

Detailed Description

This Phase II, multicenter, open-lable study is designed to evaluate the safety and efficacy of IBI110 (anti-lymphocyte activation gene 3 \[LAG-3\] monoclonal antibody) and sintilimab (anti-programmed death 1 \[PD-1\] antibody) in combination with intravenous (IV) cisplatin/carboplatin plus (+) etoposide (EP) in treatment naïve patients with extensive-stage small cell lung cancer (ES-SCLC) . Sixty eligible subjects will be enrolled and randomized in a 1:1 ratio to the experimental arm or the control arm. The experimental arm will be IBI110+ sintilimab + EP Q3W for 4 cycles, followed by IBI110+ sintilimab Q3W until disease progression. The control arm will be sintilimab + EP Q3W for 4 cycles, followed by sintilimab Q3W until disease progression.

Study Timeline

• Study First Submitted: 2021-08-16
• Study First Submitted QC: 2021-08-23
• Study First Posted: 2021-08-30
• Study Start: 2021-09-07
• Status Verified: 2022-07
• Primary Completion: 2023-02-16
• Study Completion: 2023-06-26
• Last Update Submitted: 2023-07-17
• Last Update Posted: 2023-07-19

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 60

Inclusion Criteria

1. Patients must have the ability to understand and voluntarily sign informed consent;
2. Age: over 18 years old;
3. Expected survival period ≥ 3 months;
4. Histologically or cytologically confirmed ES-SCLC (according to the Veterans Lung Administration Lung Study Group, VALG staging);
5. No prior systemic treatment for ES-SCLC;
6. Eastern Cooperative Oncology Group performance status (ECOG PS) 0 or 1;
7. At least 1 measurable lesion by computed tomography (CT) or magnetic resonance imaging (MRI) per Response Eval -uation Criteria in Solid Tumors version 1.1 (RECIST v1.1) criteria;
8. Adequate hematologic and end organ function.

Exclusion Criteria

1. Have been previously exposed to any antibody or drug of immune-mediated therapy, including but not limited to LAG-3, anti-cytotoxic T lymphocyte antigen-4 (CTLA-4), anti-PD-1, anti-PD-L1 antibodies.
2. Have received systemic treatment with Chinese herbal medicine or immunomodulatory drugs with anti-tumor indications (including thymosin, interferon, interleukin, except for local use to control pleural effusion) within 2 weeks prior to the first administration of study drug.
3. Have active or uncontrolled central nervous system (CNS) metastases and/or spinal cord compression and/or carcinomatous meningitis, or history of leptomeningeal carcinoma. Subjects with a history of radiotherapy or surgery for brain metastases and asymptomatic CNS metastases at the time of screeing are eligible if they meet all of the following criterias: have measurable lesions outside the CNS; do not have midbrain, pons, meninges, medulla oblongata or spinal cord metastases; do not have evidence of new or enlarged brain metastases after treatment for brain metastases, and corticosteroids and anticonvulsants treatments have been discontinued for at least 14 days prior to the study treatment. Subjects with asymptomatic brain metastases can be included if the brain metastases have been treated with radiotherapy and above mentioned criterias are all met.
4. Are expected to require any other antineoplastic therapy while in study (PCI is allowed).
5. Have received administration of live attenuated vaccines within 4 weeks prior to the first administration of study drug or anticipation that such a live attenuated vaccine will be required during the study.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
IBI110+Sintilimab+EP	IBI110	During each 21-day cycle, participants receive IBI110 PR2D intravenously (IV) Day 1 PLUS Sintilimab 200 mg intravenously (IV) Day 1 PLUS etoposide 100 mg/m\^2 IV on Days 1, 2 and 3 PLUS investigator's choice of platinum (carboplatin titrated to an area under the plasma drug concentration-time curve \[AUC\] 5 IV on Day 1 OR cisplatin 75 mg/m\^2 IV on Day 1). After the induction phase, participants will begin maintenance therapy with IBI110 PR2D intravenously (IV) Day 1 PLUS Sintilimab 200 mg intravenously (IV) Day 1 every 3 weeks until PD, unacceptable toxicity, withdrawal of consent, or other protocol-allowed reasons, whichever occurs first.
Sintilimab+EP	Carboplatin	During each 21-day cycle, participants receive Sintilimab 200 mg intravenously (IV) Day 1 PLUS etoposide 100 mg/m\^2 IV on Days 1, 2 and 3 PLUS investigator's choice of platinum (carboplatin titrated to an area under the plasma drug concentration-time curve \[AUC\] 5 IV on Day 1 OR cisplatin 75 mg/m\^2 IV on Day 1). After the induction phase, participants will begin maintenance therapy with Sintilimab 200 mg intravenously (IV) Day 1 every 3 weeks until PD, unacceptable toxicity, withdrawal of consent, or other protocol-allowed reasons, whichever occurs first.
Sintilimab+EP	Cisplatin	During each 21-day cycle, participants receive Sintilimab 200 mg intravenously (IV) Day 1 PLUS etoposide 100 mg/m\^2 IV on Days 1, 2 and 3 PLUS investigator's choice of platinum (carboplatin titrated to an area under the plasma drug concentration-time curve \[AUC\] 5 IV on Day 1 OR cisplatin 75 mg/m\^2 IV on Day 1). After the induction phase, participants will begin maintenance therapy with Sintilimab 200 mg intravenously (IV) Day 1 every 3 weeks until PD, unacceptable toxicity, withdrawal of consent, or other protocol-allowed reasons, whichever occurs first.
Sintilimab+EP	Etoposide	During each 21-day cycle, participants receive Sintilimab 200 mg intravenously (IV) Day 1 PLUS etoposide 100 mg/m\^2 IV on Days 1, 2 and 3 PLUS investigator's choice of platinum (carboplatin titrated to an area under the plasma drug concentration-time curve \[AUC\] 5 IV on Day 1 OR cisplatin 75 mg/m\^2 IV on Day 1). After the induction phase, participants will begin maintenance therapy with Sintilimab 200 mg intravenously (IV) Day 1 every 3 weeks until PD, unacceptable toxicity, withdrawal of consent, or other protocol-allowed reasons, whichever occurs first.
Sintilimab+EP	Sintilimab	During each 21-day cycle, participants receive Sintilimab 200 mg intravenously (IV) Day 1 PLUS etoposide 100 mg/m\^2 IV on Days 1, 2 and 3 PLUS investigator's choice of platinum (carboplatin titrated to an area under the plasma drug concentration-time curve \[AUC\] 5 IV on Day 1 OR cisplatin 75 mg/m\^2 IV on Day 1). After the induction phase, participants will begin maintenance therapy with Sintilimab 200 mg intravenously (IV) Day 1 every 3 weeks until PD, unacceptable toxicity, withdrawal of consent, or other protocol-allowed reasons, whichever occurs first.
IBI110+Sintilimab+EP	Carboplatin	During each 21-day cycle, participants receive IBI110 PR2D intravenously (IV) Day 1 PLUS Sintilimab 200 mg intravenously (IV) Day 1 PLUS etoposide 100 mg/m\^2 IV on Days 1, 2 and 3 PLUS investigator's choice of platinum (carboplatin titrated to an area under the plasma drug concentration-time curve \[AUC\] 5 IV on Day 1 OR cisplatin 75 mg/m\^2 IV on Day 1). After the induction phase, participants will begin maintenance therapy with IBI110 PR2D intravenously (IV) Day 1 PLUS Sintilimab 200 mg intravenously (IV) Day 1 every 3 weeks until PD, unacceptable toxicity, withdrawal of consent, or other protocol-allowed reasons, whichever occurs first.
IBI110+Sintilimab+EP	Sintilimab	During each 21-day cycle, participants receive IBI110 PR2D intravenously (IV) Day 1 PLUS Sintilimab 200 mg intravenously (IV) Day 1 PLUS etoposide 100 mg/m\^2 IV on Days 1, 2 and 3 PLUS investigator's choice of platinum (carboplatin titrated to an area under the plasma drug concentration-time curve \[AUC\] 5 IV on Day 1 OR cisplatin 75 mg/m\^2 IV on Day 1). After the induction phase, participants will begin maintenance therapy with IBI110 PR2D intravenously (IV) Day 1 PLUS Sintilimab 200 mg intravenously (IV) Day 1 every 3 weeks until PD, unacceptable toxicity, withdrawal of consent, or other protocol-allowed reasons, whichever occurs first.
IBI110+Sintilimab+EP	Cisplatin	During each 21-day cycle, participants receive IBI110 PR2D intravenously (IV) Day 1 PLUS Sintilimab 200 mg intravenously (IV) Day 1 PLUS etoposide 100 mg/m\^2 IV on Days 1, 2 and 3 PLUS investigator's choice of platinum (carboplatin titrated to an area under the plasma drug concentration-time curve \[AUC\] 5 IV on Day 1 OR cisplatin 75 mg/m\^2 IV on Day 1). After the induction phase, participants will begin maintenance therapy with IBI110 PR2D intravenously (IV) Day 1 PLUS Sintilimab 200 mg intravenously (IV) Day 1 every 3 weeks until PD, unacceptable toxicity, withdrawal of consent, or other protocol-allowed reasons, whichever occurs first.
IBI110+Sintilimab+EP	Etoposide	During each 21-day cycle, participants receive IBI110 PR2D intravenously (IV) Day 1 PLUS Sintilimab 200 mg intravenously (IV) Day 1 PLUS etoposide 100 mg/m\^2 IV on Days 1, 2 and 3 PLUS investigator's choice of platinum (carboplatin titrated to an area under the plasma drug concentration-time curve \[AUC\] 5 IV on Day 1 OR cisplatin 75 mg/m\^2 IV on Day 1). After the induction phase, participants will begin maintenance therapy with IBI110 PR2D intravenously (IV) Day 1 PLUS Sintilimab 200 mg intravenously (IV) Day 1 every 3 weeks until PD, unacceptable toxicity, withdrawal of consent, or other protocol-allowed reasons, whichever occurs first.

Primary Outcome Measures

Name	Time	Method
Progression-Free Survival (PFS)	Up to 5 years	PFS is defined as the time interval from ra ndomization to the date of the first docu mented tumor progression, based on inve stigator assessments (per RECIST 1.1), or death due to any cause, whichever come s first.
Incidence of Treatment-related Adverse Events(TRAE), Serious Adverse Events (SAEs) and Immune-related adverse events (irAE) nation with sintilimab and EP in untreated ES-SCLC	Up to 5 years	Evaluate the safety and tolerability profile of IBI110 + sintilimab and EP in untreated ES-SCLC . Adverse events per CTCAE v5.0 criteria guidelines will be used to assess this outcome.

Secondary Outcome Measures

Name	Time	Method
To assess the half-life(t1/2) of IBI110+Sintilimab+EP	Up to 1 year
Overall Survival(OS)	Up to 5 years	OS: Defined as the time interval from ran domization to death.
Disease control rate(DCR);	Up to 5 years	DCR: The percentage of cases that achiev ed remission (PR+CR) and stable disease (SD) after treatment accounted for the n umber of evaluable cases.
Duration of response(DOR);	Up to 5 years	DOR: Defined as the time from the first d ocumented objective response to the first documented progressive disease or deat h of any cause, whichever occurs first.
To assess the clearance(CL) of IBI110+Sintilimab+EP	Up to 1 year
Objective response rate(ORR)	Up to 5 years	ORR: Defined as the number of cases achi eving CR, or PR, as a percentage of patien ts with evaluable efficacy.
To assess the immunogenicity;	Up to 5 years	Immunogenicity: the immunogenicity: will be evaluated by determining the inciden ce of anti-drug antibodies (ADA) and furt her testing ADA-positive serum specimen s for neutralizing antibody (Nab);
To assess the Peak Plasma Concentration(Cmax) of IBI110+Sintilimab+EP	Up to 1 year
To assess the Area under the plasma concentration versus time curve(AUC) of IBI110+Sintilimab+EP	Up to 1 year
To assess the volume of distribution(V) of IBI110+Sintilimab+EP	Up to 1 year

Trial Locations

Locations (1)

Shanghai Pulmonary Hospital; 🇨🇳 Shanghai, Shanghai, China