SLC-391 + Pembrolizumab for Lung Cancer

Recruiting at 12 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

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. ^{1 2 3 4 5}

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. ^{1 3 4 6 7}

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. ^{1 2 3 4 8}

Research Team

Zaihui Zhang, PhD

Principal Investigator

SignalChem LifeSciences

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.

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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, 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]

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]

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]

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]

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]

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]

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]

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

[Prolonged response with paclitaxel after immunotherapy by pembrolizumab in lung cancer]. [2017]

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

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. [2017]

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]

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

Pembrolizumab Shows Promise for NSCLC. [2015]

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

Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. [2023]

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]

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]