AL8326 in SCLC Treatment

Sponsor

Advenchen Pharmaceuticals, LLC. (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT05363280

Collaborator

(none)

Enrollment

Location

Arms

Anticipated Duration (Months)

1.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This trial is a Phase II trial designed to evaluate the safety and efficacy of using oral AL8326 , a multi-targeted receptor Tyrosine Kinase Inhibitor( TKI) , to recurrent, advanced, or metastatic small cell lung cancer (SCLC) patients who need ≥2nd line treatment .

Condition or Disease	Intervention/Treatment	Phase
Small Cell Lung Cancer	Drug: AL8326 low dose group Drug: AL8326 middle dose group Drug: AL8326 high dose group	Phase 2

Detailed Description

This study is designed for two steps: Phase 2 Optimal Biological Dose (OBD) finding and Phase 2 expansion cohort study after OBD determination.

The Phase 2 study aims to find optimal biological dose (OBD) initially. Patients will be randomized to 3 different dosing groups in OBD finding cohorts. Each cohort will enroll 6-12 SCLC patients who need ≥2nd line treatment without or with brain metastasis which is controlled with no active hemorrhage. This OBD finding cohort will also evaluate the pharmacokinetic profile of AL8326.

A phase 2 expansion cohort will be continued if a positive clinical result would have been observed after OBD determination for 40-60 patients. Upon FDA's approval the Phase 2 expansion cohort clinical study will be further expanded to evaluate the safety and efficacy of AL8326 in patients individually with SCLC who need = or >2nd line treatment without or with brain metastasis which is controlled with no active hemorrhage.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

36 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

The phase 2 study aims to find optimal biological dose (OBD) for Phase 2 expansion cohort clinical study. Patients will be randomized to a 3 different dosing daily AL8326 groups ( low. middle. high) in 1:1:1 ratio in OBD finding cohorts. A phase 2 expansion cohort will be continued if a positive clinical result would have been observed after OBD determination.The phase 2 study aims to find optimal biological dose (OBD) for Phase 2 expansion cohort clinical study. Patients will be randomized to a 3 different dosing daily AL8326 groups ( low. middle. high) in 1:1:1 ratio in OBD finding cohorts. A phase 2 expansion cohort will be continued if a positive clinical result would have been observed after OBD determination.

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase 2 Evaluation of the Safety and Efficacy of AL8326 in ≥2nd Line Small Cell Lung Cancer (SCLC) Treatment

Anticipated Study Start Date :

Jul 1, 2022

Anticipated Primary Completion Date :

Dec 1, 2023

Anticipated Study Completion Date :

Dec 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: OBD finding cohort at low dose Subject in low dose group will receive AL8326 orally in each cycle until intolerable toxicity or disease progression or withdrawal . 6-12 subjects are in this group. Efficacy, safety and PK will be evaluated and compared within 3 different dosing group to define the final OBD.	Drug: AL8326 low dose group Taken AL3826 at low dose orally
Experimental: OBD finding cohort at middle dose Subject in middle dose group will receive AL8326 orally in each cycle until intolerable toxicity or disease progression or withdrawal . 6-12 subjects are in this group. Efficacy, safety and PK will be evaluated and compared within 3 different dosing group to define the final OBD.	Drug: AL8326 middle dose group Taken AL3826 at middle dose orally
Experimental: OBD finding cohort at high dose Subject in high dose group will receive AL8326 orally in each cycle until intolerable toxicity or disease progression or withdrawal . 6-12 subjects are in this group. Efficacy, safety and PK will be evaluated and compared within 3 different dosing group to define the final OBD.	Drug: AL8326 high dose group Taken AL3826 at high dose orally

Arm

Intervention/Treatment

Experimental: OBD finding cohort at low dose

Subject in low dose group will receive AL8326 orally in each cycle until intolerable toxicity or disease progression or withdrawal . 6-12 subjects are in this group. Efficacy, safety and PK will be evaluated and compared within 3 different dosing group to define the final OBD.

Drug: AL8326 low dose group

Taken AL3826 at low dose orally

Experimental: OBD finding cohort at middle dose

Subject in middle dose group will receive AL8326 orally in each cycle until intolerable toxicity or disease progression or withdrawal . 6-12 subjects are in this group. Efficacy, safety and PK will be evaluated and compared within 3 different dosing group to define the final OBD.

Drug: AL8326 middle dose group

Taken AL3826 at middle dose orally

Experimental: OBD finding cohort at high dose

Subject in high dose group will receive AL8326 orally in each cycle until intolerable toxicity or disease progression or withdrawal . 6-12 subjects are in this group. Efficacy, safety and PK will be evaluated and compared within 3 different dosing group to define the final OBD.

Drug: AL8326 high dose group

Taken AL3826 at high dose orally

Outcome Measures

Primary Outcome Measures

Optimal biological dose ( OBD ) [12 months]
Determine the Optimal biological dose ( OBD ) via evaluation of dose limiting toxicity (DLT) events to decide the dosing using in expanded cohort
Objective Response Rates (ORR) [12 month]
Evaluate the efficacy among 3 different dosing groups

Secondary Outcome Measures

Duration of response ( DOR) [12 months]
Measure the length of time that a tumor continues to respond to treatment without the cancer growing or spreading
Number of participants with AEs, SAEs, abnormal physical examination findings, abnormal laboratory test results, abnormal vital signs and abnormal electrocardiography (ECG) findings [12 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Major Inclusion Criteria:

Male or female, 18 years of age or older
ECOG performance status of 0 or 1
Histologically or cytologically confirmed SCLC
Have at least 1 lesion that meets the criteria for being measurable, as defined by RECIST 1.1
Have a life expectancy of at least 3 months

Major Exclusion Criteria:

Serious, non-healing wound, ulcer or bone fracture
Major surgical procedure within 28 days or minor surgical procedure performed within 7 days prior to treatment
Active bleeding or pathologic conditions that carry high risk of bleeding, such as known bleeding disorder, coagulopathy, or tumor involving major vessels
Clinically significant cardiovascular disease including uncontrolled hypertension; myocardial infarction or unstable angina within 6 months prior to enrollment; New York Heart Association (NYHA) Grade II or greater congestive heart failure serious cardiac arrhythmia requiring medication; and Grade II or greater peripheral vascular disease
Hemoptysis within 3 months prior to enrollment
Concomitant treatment with strong inhibitors or inducers of CYP3A4, CYP2C9 and CYP2C19 within 14 days prior to enrollment and during the study unless there is an emergent or life-threatening medical condition that required it.