Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

Carcinoma

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Antineoplastic Agents

All Drugs and Chemicals

Pembrolizumab

Immunomodulating Agents

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Dose level 1 dose will be SLC-391 100 mg PO/BID on Days 1-21 of each cycle and Pembrolizumab 200 mg IV on Day 1 of each cycle.

All dose-escalation decisions and the rationale for progressing to the next cohort will be reviewed by the Safety Review Committee (SRC).

A subject may continue treatment with SLC-391 and pembrolizumab in 21-day cycles until the treatment discontinuation criteria are met.

Dose level 2 dose will be SLC-391 150 mg PO/BID on Days 1-21 of each cycle and Pembrolizumab 200 mg IV on Day 1 of each cycle.

All dose-escalation decisions and the rationale for progressing to the next cohort will be reviewed by the Safety Review Committee (SRC).

Dose level -1 dose will be SLC-391 50 mg PO/BID on Days 1-21 of each cycle and Pembrolizumab 200 mg IV on Day 1 of each cycle.

All dose-escalation decisions and the rationale for progressing to the next cohort will be reviewed by the Safety Review Committee (SRC).

The dose of SLC-391 will be randomized between two dose levels as approved by the SRC in combination with Pembrolizumab.

* Tumors must have PD-L1 expression (TPS ≥1%)
* No prior systemic treatment (chemotherapy or targeted therapy) and no prior immunotherapy (SOC or investigational) in advanced or metastatic setting
* Subjects with actionable genomic alterations with approved targeted therapy in first line setting are not allowed
* Subjects with disease recurrence or progression following neoadjuvant or adjuvant therapy or definitive chemoradiation therapy are eligible.
* Prior adjuvant, neoadjuvant immunotherapy allowed if completed more than 12 months before documented relapse

A subject may continue treatment with SLC-391 and pembrolizumab in 21-day cycles until the treatment discontinuation criteria are met.

The dose of SLC-391 will be randomized between two dose levels as approved by the SRC in combination with Pembrolizumab.

* Up to 2 prior lines therapy in an advanced or metastatic setting allowed
* Must have received at least 2 doses of an approved anti-PD(L)-1 inhibitor and disease progressed either during treatment or within 12 weeks from last dose of anti-PD(L)-1 therapy
* Subjects who received treatment with a targeted therapy for an actionable genomic alteration with can participate if there is documented progressive disease or they were unable to tolerate the approved targeted therapy. Only these subjects are allowed to receive up to a maximum of 3 prior lines of cancer therapy in an advanced or metastatic setting.

A subject may continue treatment with SLC-391 and pembrolizumab in 21-day cycles until the treatment discontinuation criteria are met.

SLC-391

pembrolizumab

Zaihui Zhang, PhD

Madhu Singh, PhD

SLC-391 is a novel, potent and specific small molecule inhibitor of receptor tyrosine kinase AXL with desirable potency and pharmaceutical properties.

The study is being done to evaluate the safety and pharmacokinetic (PK) profile of SLC-391 in combination with pembrolizumab in participants with non-small cell lung cancer (NSCLC).

Each treatment cycle lasts 21 days. Participants will swallow SLC-391 pills two times every day. Participants will get pembrolizumab intravenously (IV) from the study site staff on the first day of every cycle.

This study has 2 parts. The first part will determine the recommended dose of SLC-391 in combination with pembrolizumab. The second part wants to find out if the combination of SLC-391 and pembrolizumab can help stop NSCLC tumours from growing or spreading.

Testing Experimental Anti-cancer Drug SLC-391 With an Approved Immunotherapy Drug, Pembrolizumab, for Advanced Lung Cancers

An Open-Label, Phase 1b/2a Study of SLC-391, an AXL Inhibitor, in Combination With Pembrolizumab in Subjects With Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC)

After a minimum of 3 evaluable subjects have completed the 21-day DLT (Dose Limiting Toxicity) evaluation period, SRC will review all available safety, efficacy, PK, and pharmacodynamic data and determine whether to expand the current dose level or escalate or de-escalate.

A subject is considered "evaluable" for dose-decisions during Phase 1b if the subject has completed the 21-day DLT evaluation period and has received at least 75% of the planned dose of study drug during the DLT evaluation period, or the subject has experienced a DLT. The number of subjects experiencing a DLT will inform the SRC's decision on whether to expand, escalate or de-escalate.

AEs are defined using NCI-CTCAE v5.0 and DLTs include events ≥ Grade 3 in severity with some exceptions.

To assess AEs as criteria of safety of oral SLC-391 in combination with pembrolizumab

Proportion of subjects who have achieved complete response (CR) or partial response (PR), evaluated using RECIST 1.1 for tumor assessment.

To assess AEs as criteria of safety of oral SLC-391 in combination with pembrolizumab(PR), evaluated using RECIST 1.1 for tumor assessment.

Pharmacokinetics of blood sample (plasma) levels of SLC-391 will be analyzed using validated high-performance liquid chromatography with tandem quadrupole mass spectrometry detection

ORR by RECIST (RECIST) as assessed by investigators. Defined as the proportion of subjects who have achieved complete response (CR) or partial response (PR), evaluated using RECIST 1.1 based on Investigator assessment.

Disease control rate (DCR) by RECIST 1.1 as assessed by investigators. Defined as as the percentage of subjects achieving CR, PR, or SD (Stable disease) as assessed by the Investigator per RECIST 1.1.

Time-to-response (TTR) by RECIST 1.1 as assessed by investigators.

Duration of response (DoR) by RECIST 1.1 as assessed by investigators

Progression-free survival (PFS) by RECIST 1.1 as assessed by investigators

Time-to-progression (TTP) by RECIST 1.1 as assessed by investigators

Spots Global Cancer Trial Database for Testing Experimental Anti-cancer Drug SLC-391 With an Approved Immunotherapy Drug, Pembrolizumab, for Advanced Lung Cancers

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

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Contact Details

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