IN10018 Combination Therapy in Treatment-naïve ES-SCLC

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

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).

Study Overview

• Status: Recruiting
• Conditions: Small Cell Lung Cancer Extensive Stage
• Intervention / Treatment: Drug: IN10018; Drug: Tislelizumab; Drug: Carboplatin; Drug: Etoposide

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 120
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Shu Fang; Phone Number: 86-15933968623; Email: shu.fang@inxmed.com
• Study Contact Backup: Name: Lily Li; Phone Number: 86-13911551669; Email: lily.li@inxmed.com

Study Locations

• China
  • Jinan, China
    • Recruiting
    • Shandong Province Cancer Hospital
    • Contact: Yuping Sun
  • Tianjin, China
    • Not yet recruiting
    • Tianjin Medical University Cancer Institute & Hospital
    • Contact: Peng Chen
  • Zhengzhou, China
    • Not yet recruiting
    • Henan Provincial People's Hospital
    • Contact: Shundong Cang

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria

1. Male or female aged 18-75 years old at the time of signing informed consent.
2. Be able to understand and be willing to sign informed consent.
3. Histologically confirmed ES-SCLC (according to the Veterans Administration Lung Study Group (VALG) staging system), which is not suitable for locally radical therapy.
4. Has not received any systemic antitumor therapy for ES-SCLC.
5. Has at least one measurable tumor lesion per RECIST 1.1.
6. Has an ECOG performance status of 0 or 1.
7. Estimated life expectancy is more than 3 months.
8. 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.
9. AEs due to prior antitumor therapy must be recovered to ≤ Grade 1 (CTCAE v5.0) or a steady state as assessed by investigators
10. 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

1. Has known active or untreated central nervous system (CNS) metastases, and/or carcinomatous meningitis.
2. 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.
3. Pleural, pericardial or abdominal effusion that are clinically symptomatic and require puncture or drainage.
4. Symptomatic hypercalcemia.
5. Malignancies other than the study disease within 3 years prior to the first dose of study treatment/randomization.
6. Have received palliative radiotherapy for bone metastasis within 14 days prior to the first dose of study treatment/randomization.
7. Have had allogeneic haematopoietic stem cell transplantation or organ transplantation.
8. 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.
9. 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.
10. History of idiopathic pulmonary fibrosis, idiopathic pneumonia and organizing pneumonia, and interstitial pneumonitis or active pneumonia diagnosed per imaging examination at baseline.
11. Have had FAK inhibitors treatment.
12. Has a history of major cardiovascular or cerebrovascular diseases within 6 months prior to the first dose of study treatment/randomization.
13. Have malabsorption syndrome or cannot take study drugs orally.
14. Any active infection requiring systemic therapy within 14 days prior to the first dose of study treatment.
15. Active pulmonary tuberculosis
16. Human immunodeficiency virus (HIV) infection, active hepatitis B infection, or hepatitis C infection.
17. Known hypersensitivity or allergy to IN10018, anti-PD-1/L1 monoclonal antibodies, carboplatin or etoposide or to their drug components.
18. Pregnant or lactating women or are expected to be pregnant or lactating during study treatment.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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

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

Collaborators and Investigators

• Sponsor: InxMed (Shanghai) Co., Ltd.
• Investigators: Principal Investigator: Jun Zhao, Peking University Cancer Hospital & Institute

Study record dates

Study Major Dates

• Study Start (Actual): October 30, 2023
• Primary Completion (Estimated): January 24, 2025
• Study Completion (Estimated): October 21, 2025

Study Registration Dates

• First Submitted: September 1, 2023
• First Submitted That Met QC Criteria: September 1, 2023
• First Posted (Actual): September 8, 2023

Study Record Updates

• Last Update Posted (Actual): November 21, 2023
• Last Update Submitted That Met QC Criteria: November 19, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: First-line
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Small Cell Lung Carcinoma; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antineoplastic Agents, Immunological; Carboplatin; Etoposide; Tislelizumab
• Other Study ID Numbers: IN10018-019

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No