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

Stopped early · Phase 1/Phase 2

Conditions studied: Lung Cancer, Nonsmall Cell, Lung Cancer Stage IV, Lung Cancer Metastatic

In brief

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.

Key facts

Study ID

NCT05860296

Run by

SignalChem Lifesciences Corporation

People needed

36

Starts

2023-05-31

Expected to finish

2025-12-01

Last updated by the study team

2025-12-18

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

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.
• Phase 2a Subjects additional eligibility criteria:
• Cohort 1:
• Tumors must have PD-L1 expression (TPS ≥ 1% as determined by SOC).
• Subjects are eligible to participate if they did not receive any prior therapy (SOC or investigational) or prior immunotherapy of any kind for advanced or metastatic disease. See Exclusion Criteria 1.0.
• 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.

You may not qualify if…

• Phase 2a - Cohort 1 (only) exclusion criteria:
• Subjects have tumors that have actionable genomic alterations with approved targeted therapy in first line setting are not eligible to participate.
• Subjects are not eligible if they received any prior therapy (SOC or investigational) for advanced or metastatic disease including chemotherapy, targeted therapy, or immunotherapy of any kind such as the following: pembrolizumab, an anti-PD(L)-1 or anti-programmed death ligand 2 (PD-L2) agent, or an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA4, OX40 (Tumor necrosis factor receptor superfamily, member 4), CD137(Tumor necrosis factor receptor superfamily member 9)).
• Undergone prior treatment with a known AXL inhibitor such as bemcentinib (see Section 8.2.2 for full list of AXL inhibitors).
• Received prior systemic anticancer therapy within 5 half-lives or 3 weeks, whichever is shorter, prior to starting the first dose of study drug(s). Examples of prior systemic anticancer therapy includes cytotoxic agents, targeted therapy such as small molecules, mAbs and hormonal therapy etc..
• Received immunotherapies [including but not limited to PD(L)-1 inhibitors, etc.] within 4 weeks prior to starting the first dose of study drug(s).
• Received prior radiotherapy within 2 weeks of the first dose of study drug(s) or had a history of radiation pneumonitis.
• Note: Subjects must have recovered from all radiation-related toxicities and not require corticosteroids. A 1 week washout is permitted following palliative radiation (≤ 2 weeks of radiotherapy) for non-central nervous system (CNS) disease.
• Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study drug(s).
• Note: Subjects who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks after the last dose of the previous investigational agent, follow-up is primarily non-invasive, and the subject can comply with protocol requirements.
• Has not recovered to ≤ Grade 1 or to baseline from prior cancer therapy toxicity.
• Note: Subject with ≤ Grade 2 neuropathy may be an exception to this criterion and may qualify for the study after discussion with Sponsor. Subjects with endocrine-related AEs ≤ Grade 2 requiring treatment or hormone replacement may be eligible after discussion with Sponsor.
• Note: Toxic effects also include laboratory results that have not resolved to ≤ Grade 1. Subjects with ≤ Grade 2 alopecia are an exception to this criterion.
• Has not adequately recovered from major surgery and/or complications from the procedure prior to the first dose of study drug(s).
• Pulmonary hemorrhage or hemoptysis > 2.5 mL blood within 6 weeks of screening (or within 2 weeks if the source of bleeding is treated).
• Received a live or live-attenuated vaccine within 30 days prior to the first dose of study drug(s). Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacille Calmette-Guerin, and typhoid vaccine. Seasonal influenza vaccines are generally killed virus vaccines and are permitted; however, intranasal influenza vaccines (e.g., Flu-Mist®) are live-attenuated vaccines and are not allowed.
• Note: The administration of killed vaccines, mRNA vaccines, and DNA vaccines is allowed.
• Has an active diagnosis of immunodeficiency or is receiving systemic steroid therapy (exceeding 10 mg daily of prednisone equivalent) or has received any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug(s).
• Has active autoimmune disease which required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs).
• Note: Hormone therapy (e.g., thyroxine, insulin, or corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed.
• Known additional malignancy that is progressing or has required active treatment within the past 2 years.
• Note: Subjects with curatively treated basal or squamous cell carcinoma of the skin (non-melanoma skin cancer), cervical or vaginal intra-epithelial neoplasia, non-invasive breast cancer in situ, or localized prostate cancer with a prostate-specific antigen level of < 4 ng/mL (µg/L) at screening are not excluded. Subjects with other curatively treated malignancies who have had a > 2-year disease-free interval and whose natural history or treatment does not have the potential to interfere with investigational agents (e.g., hormone maintenance) may be enrolled after approval by the Medical Monitor/Sponsor.
• Known active CNS metastases and/or carcinomatous meningitis. Subjects with adequately treated brain metastases may participate provided they meet the following criteria:
• Are radiologically stable (no progression) for at least 4 weeks as documented by screening computed tomography (CT) or magnetic resonance imaging (MRI) scan.
• Clinically stable.

Where it is running

• Community Health Network — Indianapolis, Indiana, United States
• Horizon Verdi Oncology — Lafayette, Indiana, United States
• Karmanos Cancer Center — Detroit, Michigan, United States
• Nebraska Cancer Specialists — Omaha, Nebraska, United States
• Cleveland Clinic — Cleveland, Ohio, United States
• Stephenson Cancer Center — Oklahoma City, Oklahoma, United States
• Cross Cancer Institute — Edmonton, Alberta, Canada
• Juravinski Cancer Centre — Hamilton, Ontario, Canada
• London Regional Cancer Centre — London, Ontario, Canada
• Sunnybrook Health Sciences Centre — Toronto, Ontario, Canada
• Jewish General Hospital — Montreal, Quebec, Canada
• McGill University Health Centre — Montreal, Quebec, Canada

Full record on ClinicalTrials.gov

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