IN10018 Combination Therapy in Treatment-naïve ES-SCLC

Study Overview
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Brief Summary
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This is a multicenter, open-label, Randomized, phase Ib/II clinical study to evaluate the anti-tumor efficacy, safety, tolerability, and PK of IN10018 in combination with anti-PD-1/L1 monoclonal antibody (Tislelizumab is proposed as the combination drug) and chemotherapy (platinum and etoposide) as the first-line treatment in Extensive-stage small cell lung cancer (ES-SCLC).

Detailed Description
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This study consists of 2 parts: 1) Phase Ib-Dose Confirmation part: To assess the PK parameters, safety and recommended phase II dose (RP2D) of IN10018 in combination with anti-PD-1/L1 monoclonal antibody (Tislelizumab is proposed as the combination drug), platinum (carboplatin is proposed as the combination drug) and etoposide as the first-line treatment in ES-SCLC. 2) Phase II-Dose Expansion part: To assess the antitumor efficacy, safety and tolerability in the experimental group of IN10018 in combination with Tislelizumab, carboplatin and etoposide as compared to the control group of Tislelizumab in combination with carboplatin and etoposide as the first-line treatment in ES-SCLC.

Official Title
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A Phase Ib/II Clinical Trial to Evaluate the Anti-tumor Efficacy, Safety, Tolerability, and Pharmacokinetics of IN10018 Combined With Anti-PD-1/L1 Antibody and Chemotherapy as First-line Treatment in Extensive-stage Small Cell Lung Cancer

Conditions
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Small Cell Lung Cancer Extensive Stage

Intervention / Treatment
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* Drug: IN10018
* Drug: Tislelizumab
* Drug: Carboplatin
* Drug: Etoposide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Male or female aged 18-75 years old at the time of signing informed consent. Be able to understand and be willing to sign informed consent. Histologically confirmed ES-SCLC (according to the Veterans Administration Lung Study Group (VALG) staging system), which is not suitable for locally radical therapy. Has not received any systemic antitumor therapy for ES-SCLC. Has at least one measurable tumor lesion per RECIST 1.1. Has an ECOG performance status of 0 or 1. Estimated life expectancy is more than 3 months. Has adequate organ function of bone marrow, liver, kidney, and coagulation. Relative laboratory tests must be performed within 7 days prior to first dose of study treatment/randomization. AEs due to prior antitumor therapy must be recovered to ≤ Grade 1 (CTCAE v5.0) or a steady state as assessed by investigators Subjects (male and female) with childbearing potential must agree to use contraception during the treatment phase and through 3 months after the last dose of study treatment. Exclusion Criteria Has known active or untreated central nervous system (CNS) metastases, and/or carcinomatous meningitis. Spinal cord compression without surgery and/or radiation therapy, or previously diagnosed and treated spinal cord compression without evidence that disease has been clinically stable for at least 7 days prior to the first dose of study treatment/randomization. Pleural, pericardial or abdominal effusion that are clinically symptomatic and require puncture or drainage. Symptomatic hypercalcemia. Malignancies other than the study disease within 3 years prior to the first dose of study treatment/randomization. Have received palliative radiotherapy for bone metastasis within 14 days prior to the first dose of study treatment/randomization. Have had allogeneic haematopoietic stem cell transplantation or organ transplantation. History of active autoimmune disease required systemic treatment (including but not limited to drugs for disease control, corticosteroids, or immunosuppressive drugs) within the past 2 years. Have an immunodeficiency disorder or have received systemic steroid therapy (prednisone or equivalent corticosteroid > 10 mg/day) or other immunosuppressants within 7 days prior to the first dose of study treatment/randomization. History of idiopathic pulmonary fibrosis, idiopathic pneumonia and organizing pneumonia, and interstitial pneumonitis or active pneumonia diagnosed per imaging examination at baseline. Have had FAK inhibitors treatment. Has a history of major cardiovascular or cerebrovascular diseases within 6 months prior to the first dose of study treatment/randomization. Have malabsorption syndrome or cannot take study drugs orally. Any active infection requiring systemic therapy within 14 days prior to the first dose of study treatment. Active pulmonary tuberculosis Human immunodeficiency virus (HIV) infection, active hepatitis B infection, or hepatitis C infection. Known hypersensitivity or allergy to IN10018, anti-PD-1/L1 monoclonal antibodies, carboplatin or etoposide or to their drug components. Pregnant or lactating women or are expected to be pregnant or lactating during study treatment.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental group<br>IN10018 in combination with Tislelizumab, carboplatin and etoposide as the first-line treatment in ES-SCLC. | Drug: IN10018<br>* orally taken once daily<br>* Other names: BI 853520;Drug: Tislelizumab<br>* 200mg D1, Q3W, intravenously<br>Drug: Carboplatin<br>* AUC 5 mg/ml/min, D1, Q3W, intravenously<br>Drug: Etoposide<br>* Etoposide 100 mg/m2, D1-D3, Q3W, intravenously<br>|
| Active Comparator: Control group<br>Tislelizumab in combination with carboplatin and etoposide as the first-line treatment in ES-SCLC | Drug: Tislelizumab<br>* 200mg D1, Q3W, intravenously<br>Drug: Carboplatin<br>* AUC 5 mg/ml/min, D1, Q3W, intravenously<br>Drug: Etoposide<br>* Etoposide 100 mg/m2, D1-D3, Q3W, intravenously<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To identify the Recommended phase II dose (RP2D) of IN10018 in combination with Tislelizumab, Carboplatin and Etoposide in first-line ES-SCLC. | Evaluate proportion of patients suffered with AEs defined as dose-limited toxicities (DLTs) per protocol; and RP2D will be determined per the incidence of AEs defined as DLTs. | Up to 3 years | 
| Progress free survival (PFS) of IN10018 in combination with Tislelizumab, carboplatin and etoposide as compared to Tislelizumab in combination with carboplatin and etoposide in first-line ES-SCLC per BICR based on RECIST 1.1 | Defined as the time from randomization to first documentation of disease progression or to death due to any cause, whichever comes first. | Up to 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PFS of IN10018 in combination with Tislelizumab, carboplatin and etoposide as compared to Tislelizumab in combination with carboplatin and etoposide in first-line ES-SCLC per investigator based on RECIST 1.1 | Defined as the time from randomization to first documentation of disease progression or to death due to any cause, whichever comes first. | Up to 3 years | 
| Objective response rate (ORR) of IN10018 in combination with Tislelizumab, carboplatin and etoposide as compared to Tislelizumab in combination with carboplatin and etoposide in first-line ES-SCLC per BICR and investigator based on RECIST 1.1. | Defined as the proportion of subjects with complete response (CR) or partial response (PR). | Up to 3 years | 
| Duration of objective response (DOR) of IN10018 in combination with Tislelizumab, carboplatin and etoposide as compared to Tislelizumab in combination with carboplatin and etoposide in first-line ES-SCLC per BICR and investigator based on RECIST 1.1. | Defined as the time from start of the first documentation of CR or PR to the first documentation of disease progression or to death due to any cause, whichever comes first. | Up to 3 years | 
| Disease Control Rate (DCR) of IN10018 in combination with Tislelizumab, carboplatin and etoposide as compared to Tislelizumab in combination with carboplatin and etoposide in first-line ES-SCLC per BICR and investigator based on RECIST 1.1 | Defined as the proportion of patients with CR, PR, or stable disease (SD). | Up to 3 years | 
| Overall survival (OS) of IN10018 in combination with Tislelizumab, carboplatin and etoposide as compared to Tislelizumab in combination with carboplatin and etoposide in first-line ES-SCLC. | Defined as the time from randomization to the date of death due to any cause. | Up to 3 years | 
| Number of patients with adverse event | The number of participants who experienced AEs is presented. | Up to 3 years | 
| PK: AUC of IN10018 following single dose administration and at steady state | Area under the concentration-time curve (AUC) | Up to 3 years | 
| PK: Cmax of IN10018 following single dose administration and at steady state | Maximum concentration (Cmax) | Up to 3 years | 
| PK: Ctrough of IN10018 following single dose administration and at steady state | Trough concentration (Ctrough) | Up to 3 years | 
| PK: Tmax of IN10018 following single dose administration and at steady state | Time to Cmax (Tmax) | Up to 3 years | 
| PK: t1/2 of IN10018 following single dose administration and at steady state | Elimination half-life (t1/2) | Up to 3 years | 
| PK: CL/F of IN10018 following single dose administration and at steady state | apparent clearance (CL/F) | Up to 3 years | 
| PK: Vd/F of IN10018 following single dose administration and at steady state | Apparent volume of distribution (Vd/F) | Up to 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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First-line