SLC-391 + Pembrolizumab for Lung Cancer

Recruiting in Palo Alto (17 mi)

+12 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Recruiting

Sponsor: SignalChem Lifesciences Corporation

Must not be taking: AXL inhibitors

Disqualifiers: Small cell component, Active CNS metastases, others

No Placebo Group

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, you cannot have received certain cancer therapies or immunotherapies within a few weeks before starting the trial drugs. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug pembrolizumab for lung cancer?

Pembrolizumab has been shown to improve survival rates and delay disease progression in patients with advanced non-small cell lung cancer, especially when their tumors express a protein called PD-L1. It has been approved by the FDA for use in certain lung cancer patients based on studies showing significant benefits compared to traditional chemotherapy.

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Is the combination of SLC-391 and Pembrolizumab safe for humans?

Pembrolizumab (also known as Keytruda) has been used in various cancer treatments and is generally considered safe, but it can cause side effects like pneumonitis (lung inflammation) in 1%-5% of patients. While specific safety data for the combination with SLC-391 is not provided, pembrolizumab's safety profile is well-documented in other studies.

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What makes the drug SLC-391 + Pembrolizumab unique for lung cancer treatment?

The combination of SLC-391 with Pembrolizumab is unique because Pembrolizumab is a PD-1 inhibitor that helps the immune system attack cancer cells, and it has shown effectiveness in treating various cancers, including lung cancer. This combination may offer a novel approach by potentially enhancing the immune response against lung cancer compared to using Pembrolizumab alone.

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Eligibility Criteria

This trial is for adults with advanced non-small cell lung cancer (NSCLC) who have a life expectancy of at least 3 months and are in relatively good physical condition. They must have received prior treatments, including an anti-PD(L)-1 monoclonal antibody unless they couldn't tolerate it. Participants should not be pregnant or nursing, agree to use contraception if applicable, and cannot have certain severe health conditions or allergies.

Inclusion Criteria

My lung cancer is advanced but not suitable for surgery or aimed cure treatments.

I have had no more than 4 treatments for my advanced cancer.

My cancer came back or got worse after initial treatment.

Exclusion Criteria

I have an autoimmune disease treated with medication in the last 2 years.

A history or current evidence of any severe acute or chronic medical or psychiatric condition that requires treatment, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject, in the opinion of the Principal Investigator (PI; also referred to as Investigator).

I cannot take pills by mouth or have a GI condition that affects medication absorption.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Determine the recommended dose of SLC-391 in combination with pembrolizumab. Participants receive SLC-391 and pembrolizumab in 21-day cycles.

21 days per cycle

1 visit per cycle (in-person)

Treatment

Participants receive SLC-391 and pembrolizumab in 21-day cycles to evaluate safety and pharmacokinetics.

Up to 24 months

1 visit per cycle (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

90 days

Participant Groups

The trial is testing SLC-391, a new drug that targets a specific protein involved in cancer growth, alongside Pembrolizumab, an approved immunotherapy drug. The study has two parts: the first part determines the best dose of SLC-391 when used with Pembrolizumab; the second part checks if this combination can halt tumor growth in NSCLC.

Group I: ICI-Resistant (Phase 2a) Experimental Treatment 2 Interventions

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.

Group II: ICI-Naïve (Phase 2a) Experimental Treatment 2 Interventions

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.

Group III: Dose Escalation (Phase 1b Dose Level 2) Experimental Treatment 2 Interventions

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).

Group IV: Dose Escalation (Phase 1b Dose Level 1) Experimental Treatment 2 Interventions

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.

Group V: Dose Escalation (Phase 1b Dose Level -1) Experimental Treatment 2 Interventions

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).

Pembrolizumab is already approved in United States, European Union, United Kingdom for the following indications:

🇺🇸 Approved in United States as KEYTRUDA for:

• Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
• Melanoma
• Non-small cell lung cancer (NSCLC)
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Hepatocellular carcinoma
• Renal cell carcinoma
• Cervical cancer
• Endometrial carcinoma

🇪🇺 Approved in European Union as KEYTRUDA for:

• Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
• Melanoma
• Non-small cell lung cancer (NSCLC)
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Hepatocellular carcinoma
• Renal cell carcinoma
• Cervical cancer
• Endometrial carcinoma

🇬🇧 Approved in United Kingdom as KEYTRUDA for:

• Untreated metastatic or unresectable recurrent head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Verdi Cancer & Research Center Dallas, TX

Stephenson Cancer Center Oklahoma City, OK

McGill University Health Centre Montréal, Canada

Community Health Network Indianapolis, IN

More Trial Locations

Who Is Running the Clinical Trial?

SignalChem Lifesciences Corporation Lead Sponsor

Merck Sharp & Dohme LLC Industry Sponsor

References

1. Ireland pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. [2022] A phase II trial investigating the therapeutic effect of neoadjuvant programmed cell death 1 (PD-1) inhibitor pembrolizumab (MK-3475, KEYTRUDA®) administered prior to surgery for the treatment of non-small cell lung cancer (NSCLC) has been conducted (NCT03197467). We report the first clinical results of a planned interim safety analysis after 15 patients were enrolled.

2. France pubmed.ncbi.nlm.nih.gov

[Prolonged response with paclitaxel after immunotherapy by pembrolizumab in lung cancer]. [2017] Pembrolizumab, a humanized monoclonal antibody IgG4 anti-PD-1, having offered promising results in patients suffering from non-small cell lung cancer metastatic and heavily pretreated.

3. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. [2017] New insights into the interaction between the immune system and the tumor microenvironment have led to the development of checkpoint inhibitors that target the PD-1/PD-L1 pathway. Pembrolizumab (MK-3475, lambrolizumab, Keytruda(®)) is a PD-1 inhibitor that has shown clinical activity in a variety of solid tumors and is currently approved for the second-line treatment of PD-L1-positive non-small-cell lung cancer and for unresectable/metastatic melanoma. This article will discuss the results of early-phase trials of pembrolizumab in thoracic malignancies as well as ongoing studies aimed to confirm clinical benefit.

4. England pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for Treatment of Metastatic Non-Small Cell Lung Cancer: First-Line Therapy and Beyond. [2022] On October 24, 2016, the U.S. Food and Drug Administration (FDA) approved pembrolizumab (Keytruda; Merck & Co., Inc., https://www.merck.com) for treatment of patients with metastatic non-small cell lung cancer (mNSCLC) whose tumors express programmed death-ligand 1 (PD-L1) as determined by an FDA-approved test, as follows: (a) first-line treatment of patients with mNSCLC whose tumors have high PD-L1 expression (tumor proportion score [TPS] ≥50%), with no epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) genomic tumor aberrations, and (b) treatment of patients with mNSCLC whose tumors express PD-L1 (TPS ≥1%), with disease progression on or after platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving pembrolizumab.Approval was based on two randomized, open-label, active-controlled trials demonstrating statistically significant improvements in progression-free survival (PFS) and overall survival (OS) for patients randomized to pembrolizumab compared with chemotherapy. In KEYNOTE-024, patients with previously untreated mNSCLC who received pembrolizumab (200 mg intravenously [IV] every 3 weeks) had a statistically significant improvement in OS (hazard ratio [HR] 0.60; 95% confidence interval [CI]: 0.41-0.89; p = .005), and significant improvement in PFS (HR 0.50; 95% CI: 0.37-0.68; p < .001). In KEYNOTE-010, patients with disease progression on or after platinum-containing chemotherapy received pembrolizumab IV 2 mg/kg, 10 mg/kg, or docetaxel 75 mg/m2 every 3 weeks. The HR and p value for OS was 0.71 (95% CI: 0.58-0.88), p < .001 comparing pembrolizumab 2 mg/kg with chemotherapy and the HR and p value for OS was 0.61 (95% CI: 0.49-0.75), p < .001 comparing pembrolizumab 10 mg/kg with chemotherapy.

5. United States pubmed.ncbi.nlm.nih.gov

Pembrolizumab Shows Promise for NSCLC. [2015] Data from the KEYNOTE-001 trial show that pembrolizumab improves clinical outcomes for patients with advanced non-small cell lung cancer, and is well tolerated. PD-L1 expression in at least 50% of tumor cells correlated with improved efficacy.

6. England pubmed.ncbi.nlm.nih.gov

Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. [2023] Pembrolizumab (Keytruda) is a monoclonal antibody against the programmed cell death-1 (PD-1) receptor on lymphocytes, which is one of the immune checkpoint inhibitors (ICIs) approved for multiple solid and hematologic malignancies. Although ICIs have proven to be more effective and less toxic compared to chemotherapy, there are reports of adverse side effects with ICIs. For example, pneumonitis is a potentially lethal side effect occurring in 1%-5% of patients who received ICIs in clinical trials, and there are case reports with clinical and radiological features of checkpoint inhibitor-pneumonitis (CIP).

7. United States pubmed.ncbi.nlm.nih.gov

First-line pembrolizumab for non-small cell lung cancer patients with PD-L1 ≥50% in a multicenter real-life cohort: The PEMBREIZH study. [2021] The KEYNOTE-024 trial demonstrated that pembrolizumab, a PD-1 inhibitor, significantly improves progression-free survival (PFS) and overall survival (OS) in selected patients with previously untreated advanced non-small cell lung cancer (NSCLC) with a PD-L1 tumor proportion score (TPS) ≥50% and without EGFR/ALK aberrations. The main aim of this study was to report the efficacy and safety profile of pembrolizumab in real-life conditions.

8. United States pubmed.ncbi.nlm.nih.gov

Pembrolizumab as First-Line Palliative Therapy in PD-L1 Overexpressing (≥ 50%) NSCLC: Real-world Results with Special Focus on PS ≥ 2, Brain Metastases, and Steroids. [2022] Pembrolizumab is a highly effective standard of care in PD-L1 overexpressing (≥ 50%) non-small-cell lung cancer. However, a substantial share of patients from everyday clinical practice is treated without clear evidence from clinical trials.