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

NCT05860296 | Terminated Phase 1 DMC FDA Drug

• 3 other identifiers: SLC-391-102KEYNOTE-C62MK3475-C62
• Study Type: interventional
• Target: 36
• Locations: 2 countries
• Sites: 12

Brief Summary

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.

Conditions

Lung Cancer, Nonsmall Cell; Lung Cancer Stage IV; Lung Cancer Metastatic

Outcome Measures

Primary Outcomes (4)

• Phase 1b: Determine doses of SLC-391 in combination with pembrolizumab for further evaluation in Phase 2a.

  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.

  DLTs will be evaluated during the during the first 21 days of treatment Cycle 1 in the Phase 1b portion of the study.

• Phase 1b: Number of Participants with Adverse Events (AEs) as assessed by CTCAE V5.0

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

  From first dose through 90-days following cessation of SLC-391 and pembrolizumab

• Phase 2a: Antitumor activity of SLC-391 (objective response rate [ORR]) in combination with pembrolizumab, using RECIST version 1.1

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

  From date of baseline tumor assessment to the date of first documented CR or PR, assessed up to 24 months.

• Phase 2a: Number of Participants with Adverse Events (AEs) as assessed by CTCAE V5.0

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

  From first dose through 90-days following cessation of SLC-391 and pembrolizumab

Secondary Outcomes (10)

• Phase 2a: Optimal Biological Dose (OBD) of SLC-391 in combination with pembrolizumab.

  Up to 24 months

• Phase 1b and Phase 2a: Number of Participants with Adverse Events (AEs) as assessed by CTCAE V5.0

  From first dose through 90-days following cessation of SLC-391 and pembrolizumab

• Phase 1b and Phase 2a: Plasma levels of SLC-391 when administered in combination with pembrolizumab

  On Day 1 of Cycles 1,2,4,6,8,10,12 (each cycle is 21 days) and the date of first objective response by RECIST 1.1, assessed up to 24 months.

• Phase 1b: ORR of participants treated with SLC-391 in combination with pembrolizumab

  Up to 24 months

• Phase 1b and Phase 2a: Disease control rate (DCR) of participants treated with SLC-391 in combination with pembrolizumab

  Up to 24 months

Study Arms (5)

Dose Escalation (Phase 1b Dose Level 1)

EXPERIMENTAL

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.

Drug: SLC-391; Biological: pembrolizumab

Dose Escalation (Phase 1b Dose Level 2)

EXPERIMENTAL

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).

Drug: SLC-391; Biological: pembrolizumab

Dose Escalation (Phase 1b Dose Level -1)

EXPERIMENTAL

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).

Drug: SLC-391; Biological: pembrolizumab

ICI-Naïve (Phase 2a)

EXPERIMENTAL

The dose of SLC-391 will be randomized between two dose levels (50 mg and 100 mg PO/BID) 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.

Drug: SLC-391; Biological: pembrolizumab

ICI-Resistant (Phase 2a)

EXPERIMENTAL

The dose of SLC-391 will be randomized between two dose levels (50 mg and 100 mg PO/BID) as approved by the SRC in combination with Pembrolizumab. * Received at least 2 doses of anti-PD(L)-1 monoclonal antibody (mAb) in an advanced or metastatic setting. * Progressive disease documented during treatment or within 12 weeks from the last dose of anti-PD(L)-1 mAb. * Maximum of 2 prior lines of cancer therapy in an advanced or metastatic setting including an anti-PD(L)-1 mAb administered either as monotherapy or in combination with other therapies. * Subjects who received a targeted therapy for an actionable genomic alteration can participate with documented disease progression or if unable to tolerate the 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.

Drug: SLC-391; Biological: pembrolizumab

Interventions

SLC-391 DRUG

SLC-391 is an AXL inhibitor

Dose Escalation (Phase 1b Dose Level -1); Dose Escalation (Phase 1b Dose Level 1); Dose Escalation (Phase 1b Dose Level 2); ICI-Naïve (Phase 2a); ICI-Resistant (Phase 2a)

pembrolizumab BIOLOGICAL

Immunotherapy

Also known as: KEYTRUDA®

Dose Escalation (Phase 1b Dose Level -1); Dose Escalation (Phase 1b Dose Level 1); Dose Escalation (Phase 1b Dose Level 2); ICI-Naïve (Phase 2a); ICI-Resistant (Phase 2a)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The subject provides written informed consent.
• Adults ≥ 18 years of age on day of signing informed consent.
• Disease must be measurable per RECIST 1.1, as assessed by the Site(s) Investigator/radiologist. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in these lesions.
• Subject has histologically or cytologically documented, locally advanced (Stage IIIB or IIIC) disease (not candidate for surgical resection, local therapies with curative intent, or definitive chemoradiation) or the subject has metastatic NSCLC (Stage IV). Staging will be based on the American Joint Committee on Cancer, Eighth Edition. Subjects with adenocarcinoma, large cell carcinoma, undifferentiated carcinoma, squamous carcinoma, or mixed histology are eligible. Subjects with a small cell component are not eligible.
• Phase 1b Subjects additional eligibility criteria:
• Subjects must have received a minimum of one prior systemic treatment for advanced unresectable or metastatic NSCLC and progressed following prior SOC.
• Maximum of up to 4 prior lines of therapy in an advanced or metastatic setting is allowed.
• Subjects who had disease recurrence or progression following neoadjuvant or adjuvant therapy or definitive chemoradiation therapy are eligible.
• Subjects who received treatment with an approved/available targeted therapy for an actionable genomic alteration (including but not limited to EGFR, ALK, ROS1, KRAS, etc.) can participate if they have documented disease progression or were unable to tolerate the approved targeted therapy.
• Phase 1b Notes:
• Targeted therapy for advanced setting is counted as a prior line of therapy.
• Prior use of a PD(L)-1, anti-CTLA-4 (Cytotoxic T-lymphocyte associated protein 4) antibody, or any other antibody or drug that specifically targets immune checkpoint pathway is allowed and is counted as a prior line of therapy.
• Neoadjuvant and adjuvant therapies initiated \< 12 months prior to the first dose of study drug(s) will be counted as one prior line of therapy for advanced setting.
• Neoadjuvant and adjuvant therapies initiated ≥ 12 months prior to the first dose of study drug(s) are not counted as prior lines of therapy.
• Maintenance therapy is not counted as a prior line of therapy.

You may not qualify if:

• Subjects with disease recurrence or progression following neoadjuvant or adjuvant therapy or definitive chemoradiation therapy are eligible.
• Prior adjuvant or neoadjuvant immunotherapy is allowed if completed more than 12 months before documented relapse.
• Cohort 2:
• Subjects should have received at least 2 doses of an approved anti PD(L) 1 monoclonal antibody (mAb) in an advanced or metastatic setting.
• Progressive disease should be documented during treatment or within 12 weeks from the last dose of anti-PD(L)-1 mAb.
• Up to a maximum of 2 prior lines of approved cancer therapy in an advanced or metastatic setting, including an anti-PD(L)-1 mAb administered either as monotherapy or in combination with other therapies, is allowed.
• Subjects who received treatment with an approved/available targeted therapy for an actionable genomic alteration (including but not limited to EGFR, ALK, ROS1, KRAS, etc.) can participate if they have documented disease progression or 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.
• Subjects with disease recurrence or progression following neoadjuvant or adjuvant therapy or definitive chemoradiation therapy are eligible.
• Cohort 2 Notes:
• Targeted therapy for advanced setting is counted as a prior line of therapy.
• Maintenance therapy is not counted as a prior line of therapy.
• Neoadjuvant and adjuvant therapies initiated \< 12 months prior to first dose of study drug(s) will be counted as one prior line of therapy for advanced setting.
• Neoadjuvant and adjuvant therapies initiated ≥ 12 months prior to first dose of study drug(s) are not counted as prior lines of therapy.
• Subject has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Life expectancy of at least 3 months.

Sponsors & Collaborators

• SignalChem Lifesciences Corporation: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (12)

Community Health Network

Indianapolis, Indiana, 46250, United States

Location

Horizon Verdi Oncology

Lafayette, Indiana, 47905, United States

Location

Karmanos Cancer Center

Detroit, Michigan, 48201, United States

Location

Nebraska Cancer Specialists

Omaha, Nebraska, 68130, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Stephenson Cancer Center

Oklahoma City, Oklahoma, 73104, United States

Location

Cross Cancer Institute

Edmonton, Alberta, Canada

Location

Juravinski Cancer Centre

Hamilton, Ontario, Canada

Location

London Regional Cancer Centre

London, Ontario, Canada

Location

Sunnybrook Health Sciences Centre

Toronto, Ontario, Canada

Location

Jewish General Hospital

Montreal, Quebec, H3T 1E2, Canada

Location

McGill University Health Centre

Montreal, Quebec, H4A 3J1, Canada

Location

Related Publications (1)

• Zhang Z, Morrison D, Lu L, Singh M, Yan J, Leighl N, Laurie SA, Hotte S. First-in-Human Phase I Clinical Trial of SLC-391, a Novel and Selective AXL Inhibitor, in Patients with Advanced Solid Tumours. Pharmaceuticals (Basel). 2025 Dec 17;18(12):1898. doi: 10.3390/ph18121898.

  PMID: 41471387 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Lung Neoplasms

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Zaihui Zhang, PhD

  SignalChem LifeSciences

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 27, 2023
• First Posted: May 16, 2023
• Study Start: May 31, 2023
• Primary Completion: December 1, 2025
• Study Completion: December 1, 2025
• Last Updated: December 18, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

CA (6); US (6)