SLC-391 + Pembrolizumab for Lung Cancer

Recruiting at 14 trial locations

Overseen By Madhu Singh, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: SignalChem Lifesciences Corporation

Must not be taking: AXL inhibitors

Disqualifiers: Small cell component, Active CNS metastases, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 2

Duration: Up to 24 months

92 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and effectiveness of a new drug combination for non-small cell lung cancer (NSCLC), using SLC-391 (an experimental treatment) with pembrolizumab. Researchers aim to determine if this combination can stop lung cancer tumors from growing or spreading. The trial explores different doses to identify the most effective and safest option. People with advanced lung cancer, who have either not received specific treatments before or have experienced a recurrence after treatment, might be suitable for this study. Participants will take SLC-391 pills twice daily and receive pembrolizumab through an IV every three weeks.

As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that pembrolizumab, also known as Keytruda, is a well-known treatment for non-small cell lung cancer (NSCLC). Studies have found that it is usually well-tolerated. In large studies, pembrolizumab demonstrated a lasting benefit in helping people live longer when combined with chemotherapy for lung cancer.

In contrast, SLC-391 is a newer treatment under study. It aims to stop cancer cells from growing and dividing. Early evidence suggests it might be effective, but researchers are still collecting safety data. The current trial is in its early stages, with researchers working to find the safest dose and monitoring for any side effects.

In summary, pembrolizumab has a proven safety record in lung cancer treatment, while SLC-391 is still under investigation to ensure its safety when used with pembrolizumab. Trial participants are closely monitored to ensure their safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about SLC-391 combined with Pembrolizumab for lung cancer because this treatment approach offers a potentially novel mechanism of action. Unlike traditional treatments that may focus solely on targeting PD-L1 expression, SLC-391, when combined with Pembrolizumab, aims to enhance the immune response against cancer cells even in patients who are naïve or resistant to immune checkpoint inhibitors (ICIs). This combination could potentially offer new hope for patients who have limited options with existing therapies. Additionally, the specific targeting of different dose levels and stages of resistance provides a tailored approach to treatment, which could result in more effective management of lung cancer.

What evidence suggests that this trial's treatments could be effective for non-small cell lung cancer?

Research shows that pembrolizumab, combined with chemotherapy, is a common treatment for non-small cell lung cancer (NSCLC). It helps the immune system find and attack cancer cells. SLC-391 is a new drug that blocks a protein called AXL, which aids cancer cell growth and spread. Early studies suggest that SLC-391 can stop cancer cells from multiplying, causing them to die. This trial tests whether SLC-391 with pembrolizumab can more effectively prevent tumors from growing or spreading in NSCLC. Initial results appear promising, but further research is needed to confirm its effectiveness. ^{1 2 4 5 6}

Who Is on the Research Team?

Zaihui Zhang, PhD

Principal Investigator

SignalChem LifeSciences

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Pembrolizumab
• SLC-391

Trial Overview 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.

How Is the Trial Designed?

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

Who Is Running the Clinical Trial?

SignalChem Lifesciences Corporation

Lead Sponsor

Trials

4

Recruited

160+

Merck Sharp & Dohme LLC

Industry Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Published Research Related to This Trial

In a study of 153 patients with non-small-cell lung cancer treated with pembrolizumab, the median overall survival was 22 months, and the treatment showed similar efficacy to clinical trials, particularly in patients meeting KEYNOTE-024 trial criteria.

Patients with a performance status (PS) of 2 or higher, symptomatic brain metastases, or those on steroids had significantly reduced survival, indicating that while pembrolizumab can be effective, it may not benefit the most frail patients.

NCBI (Pubmed)

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. Frost, N., Kollmeier, J., Misch, D., et al.[2022]

Pembrolizumab, a PD-1 inhibitor, has demonstrated clinical effectiveness in treating various solid tumors, particularly in patients with PD-L1-positive non-small-cell lung cancer and unresectable/metastatic melanoma.

Early-phase trials and ongoing studies are focused on further confirming the clinical benefits of pembrolizumab in thoracic malignancies, highlighting its potential as a significant treatment option in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. Karim, S., Leighl, N.[2017]

A 68-year-old patient with stage IV lung adenocarcinoma showed an unexpected positive response to paclitaxel after failing treatment with pembrolizumab, an anti-PD-1 immunotherapy.

The patient experienced a response duration of over fourteen months with paclitaxel, suggesting that combining or sequencing chemotherapy with immunotherapy may enhance treatment effectiveness in certain cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Prolonged response with paclitaxel after immunotherapy by pembrolizumab in lung cancer]. Zapata, E., Mennecier, B., Leduc, C., et al.[2017]

Pembrolizumab (Keytruda) was approved by the FDA for treating metastatic non-small cell lung cancer (mNSCLC) in patients with tumors expressing PD-L1, showing significant improvements in overall survival (OS) and progression-free survival (PFS) in two major clinical trials with thousands of participants.

In the KEYNOTE-024 trial, pembrolizumab demonstrated a 40% reduction in the risk of death compared to chemotherapy, while in the KEYNOTE-010 trial, it also showed a significant survival advantage over chemotherapy in patients who had previously progressed on treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for Treatment of Metastatic Non-Small Cell Lung Cancer: First-Line Therapy and Beyond. Pai-Scherf, L., Blumenthal, GM., Li, H., et al.[2022]

Pembrolizumab, an immune checkpoint inhibitor, can cause pneumonitis in 1%-5% of patients, and this case report highlights an atypical presentation of this side effect in a patient with metastatic squamous cell carcinoma.

The patient was successfully treated with steroid therapy after ruling out other potential causes, leading to complete resolution of the pneumonitis, emphasizing the importance of recognizing and managing atypical cases of checkpoint inhibitor-pneumonitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. Jeon, WJ., Nguyen, J., Castillo, DR., et al.[2023]

The KEYNOTE-001 trial demonstrated that pembrolizumab significantly improves clinical outcomes for patients with advanced non-small cell lung cancer, indicating its efficacy as a treatment option.

Patients whose tumors express PD-L1 in at least 50% of cells showed better responses to pembrolizumab, suggesting that PD-L1 expression is a key factor in predicting treatment effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab Shows Promise for NSCLC. [2015]

In a phase II trial involving 15 patients with resectable non-small cell lung cancer (NSCLC), neoadjuvant treatment with pembrolizumab showed a major pathologic response in 27% of patients, indicating promising antitumor activity before surgery.

The treatment was found to be feasible and safe, with only 33% of patients experiencing moderate adverse events, and no postoperative mortality, suggesting that pembrolizumab does not compromise surgical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. Eichhorn, F., Klotz, LV., Kriegsmann, M., et al.[2022]

In a real-life study of 108 patients with advanced non-small cell lung cancer (NSCLC) and a PD-L1 tumor proportion score of ≥50%, pembrolizumab showed a median progression-free survival of 10.1 months, similar to results from the KEYNOTE-024 trial.

The treatment was generally well-tolerated, with only 8% of patients experiencing grade 3 adverse events, and no severe (grade 4 or 5) adverse events reported, indicating a favorable safety profile.

NCBI (Pubmed)

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. Amrane, K., Geier, M., Corre, R., et al.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05860296

NCT05860296 | Testing Experimental Anti-cancer Drug ... 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 ...

2. keytruda.com keytruda.com/non-small-cell-lung-cancer/combination-therapy-clinical-trial-results/

Advanced Nonsquamous NSCLC Combination Therapy See results of a clinical trial for a combination therapy for certain patients with advanced nonsquamous non–small cell lung cancer.

3. withpower.com withpower.com/trial/phase-2-lung-neoplasms-4-2023-2d715

SLC-391 + Pembrolizumab for Lung Cancer 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 ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10844541/

Pembrolizumab-combination therapy for NSCLC Pembrolizumab combined with chemotherapy has become the standard of care for patients with non-small-cell lung cancer (NSCLC)

5. lifesciencesbc.ca lifesciencesbc.ca/members/signalchem-enters-a-clinical-trial-collaboration-with-merck-to-evaluate-the-effect-of-slc-391-in-combination-with-keytruda-pembrolizumab-in-advanced-non-small-cell-lung-cancer/

SignalChem Enters a Clinical Trial Collaboration with ... SLC-391 disrupts cell division, inhibiting tumor growth and causing cancer cells to die. Based on emerging evidence, a clinical investigation ...

6. merck.com merck.com/news/five-year-data-for-mercks-keytruda-pembrolizumab-plus-chemotherapy-showed-sustained-survival-benefit-versus-chemotherapy-alone-in-two-studies-for-metastatic-non-small-cell-lung-cancer-nsclc/

Five-Year Data for Merck's KEYTRUDA® (pembrolizumab ... Five-year overall survival rate of 19.4% and 18.4% for KEYTRUDA plus chemotherapy in KEYNOTE-189 and KEYNOTE-407, respectively.