This Phase II/III, Multicenter Study is Designed to Evaluate the Safety and Clinical Activity of AL3810 in Patients

Study Overview
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Brief Summary
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Phase II Study is to Evaluate the Safety and tolerability of AL3810 in combination with carboplatin plus (+) etoposide in untreated participants with ES-SCLC. Phase III Study is to Evaluate the efficacy of AL3810 in combination with carboplatin plus (+) etoposide in untreated participants with ES-SCLC.

Official Title
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Multicenter, Phase II/III Study of Carboplatin Plus Etoposide With AL3810 in Participants With Untreated Extensive-Stage (ES) Small Cell Lung Cancer (SCLC)

Conditions
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Extensive-stage Small Cell Lung Cancer

Intervention / Treatment
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* Drug: AL3810
* Drug: carboplatin + etoposide
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed Informed Consent Form Male or female, 18  75years of age Eastern Cooperative Oncology Group(ECOG) performance status of 0 or 1 Histologically or cytologically confirmed ES-SCLC No prior treatment for ES-SCLC Measurable disease, as defined by RECIST v1.1 Adequate hematologic and end organ function. Serum pregnancy test in screening period for women of childbearing potential should be negative.Except for women who have a history of sterilization or are postmenopausal.Men or woman subjects of reproductive age and their partners must agree to use effective contraception for at least 6 months from the date of signing the Informed Consent Form(ICF) until the last dose of the investigational therapy. exclusion criteria: main exclusion criteria Histologically confirmed mixed small cell lung cancer. Symptoms related to central nervous system(CNS) metastasis, unstable CNS metastasis, or CNS diseases needed the increase of steroid dosage to control. Uncontrolled hypertension.

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: Sequential Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose escalation (AL3810 + carboplatin + etoposide)<br>Phase II:Participants will receive AL3810 orally in combination with carboplatin and etoposide during the Cycles 1-4 . AL3810 dose escalated form 5mg to 10mg step-up to determine the recommended dose of AL3810 in combination with carboplatin plus (+) etoposide in untreated participants with ES-SCLC. | Drug: AL3810<br>* 5mgQD, 7.5mgQD, 10mgQD<br>* Other names: E-3810;Drug: carboplatin + etoposide<br>* Carboplatin and etoposide are background treatment.<br>|
| Experimental: AL3810+ carboplatin + etoposide<br>Phase III:Participants will receive AL3810(recommended dose will be determined by safety monitoring committee (SMC) in Phase II) orally in combination with carboplatin and etoposide during the Cycles 1-4. Thereafter, participants will receive maintenance AL3810 until persistent radiographic PD, intolerable toxicity or withdrawal of consent, investigator's consideration, lost follow up, death ,study termination by the sponsor.whichever occurs first. | Drug: AL3810<br>* 5mgQD, 7.5mgQD, 10mgQD<br>* Other names: E-3810;Drug: carboplatin + etoposide<br>* Carboplatin and etoposide are background treatment.<br>|
| Placebo Comparator: Placebo+ carboplatin + etoposide<br>Phase III:Participants will receive placebo orally in combination with carboplatin and etoposide during the induction Cycles 1-4. Thereafter, participants will receive maintenance placebo until persistent radiographic PD, intolerable toxicity or withdrawal of consent, investigator's consideration, lost follow up, death ,study termination by the sponsor.whichever occurs first. | Drug: carboplatin + etoposide<br>* Carboplatin and etoposide are background treatment.<br>Drug: Placebo<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase II:adverse event(AE)/serious adverse event(SAE) | AE/SAE to find the recommended dose of AL3810 | From the date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months | 
| Phase III:1.PFS | 1. Duration of Progression-Free Survival (PFS) as Assessed by the Independent Review Committee Using RECIST v1.1 | From the date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 56 months |