SX-682 With Pembrolizumab for the Treatment of Metastatic or Recurrent Stage IIIC or IV Non-Small Cell Lung Cancer

NCT05570825 | Recruiting Phase 2 DMC FDA Drug

• 4 other identifiers: RG1122737NCI-2022-07428P50CA22894411019
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial tests whether CXCR1/2 inhibitor SX-682 (SX-682) with pembrolizumab works to treat patients with stage IIIC or IV non-small cell lung cancer that has spread to other parts of the body (metastatic) or that has come back (recurrent). SX-682 is a drug that binds to receptors on some types of immune and cancer cells, inhibiting signaling pathways, reducing inflammation, and allowing other types of immune cells to kill and eliminate cancer cells. Pembrolizumab is a monoclonal antibody that binds to a receptor called PD-1 that is found on the surface of T-cells (a type of immune cell), activating an immune response against tumor cells. Giving SX-682 in combination with pembrolizumab may be more effective at treating patients with metastatic or recurrent non-small cell lung cancer than giving these treatments alone.

Conditions

Metastatic Lung Non-Small Cell Carcinoma; Recurrent Lung Non-Small Cell Carcinoma; Stage IIIC Lung Cancer AJCC v8; Stage IV Lung Cancer AJCC v8

Outcome Measures

Primary Outcomes (1)

• Best objective response rate

  Response is defined as a complete response (CR) or partial response (PR) as best objective response. For the primary analyses, binary proportions will be estimated along with 90% confidence intervals (consistent with 1-sided 5% level testing).

  Up to 6 years

Secondary Outcomes (6)

• Response rate within subgroups

  Up to 6 years

• Disease control rate

  Up to 6 years

• Duration of response

  Date of first documentation of confirmed response (CR or PR) to date of first documentation of progression, assessed up to 6 years

• Progression-free survival

  Date of study registration to date of first documentation of progression, assessed up to 6 years

• Overall survival

  Date of study registration to date of death due to any cause, assessed up to 6 years

Study Arms (1)

Treatment (SX-682, pembrolizumab)

EXPERIMENTAL

Patients receive SX-682 PO BID, starting 7 days prior to the start of pembrolizumab, and pembrolizumab IV over 30 minutes on day 1. Cycles repeat every 3 weeks for up to 24 months in the absence of disease progression or unacceptable toxicity. Patients also undergo biopsy and PET/CT or CT at screening and on study and undergo MRI and collection of blood samples at screening, throughout the study, and during follow up.

Procedure: Biopsy; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Drug: CXCR1/2 Inhibitor SX-682; Procedure: Magnetic Resonance Imaging; Biological: Pembrolizumab; Procedure: Positron Emission Tomography

Interventions

Biopsy PROCEDURE

Undergo biopsy

Also known as: BIOPSY_TYPE, Bx

Treatment (SX-682, pembrolizumab)

Biospecimen Collection PROCEDURE

Undergo collection of blood samples

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Treatment (SX-682, pembrolizumab)

Computed Tomography PROCEDURE

Undergo PET/CT or CT

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized Tomography, CT, CT Scan, tomography

Treatment (SX-682, pembrolizumab)

CXCR1/2 Inhibitor SX-682 DRUG

Given PO

Also known as: SX 682, SX-682, SX682

Treatment (SX-682, pembrolizumab)

Magnetic Resonance Imaging PROCEDURE

Undergo MRI

Also known as: Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging

Treatment (SX-682, pembrolizumab)

Pembrolizumab BIOLOGICAL

Given IV

Also known as: Keytruda, Lambrolizumab, MK-3475, SCH 900475, BCD-201, Pembrolizumab Biosimilar BCD-201, GME 751

Treatment (SX-682, pembrolizumab)

Positron Emission Tomography PROCEDURE

Undergo PET/CT

Also known as: Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron Emission Tomography Scan, Positron-Emission Tomography, proton magnetic resonance spectroscopic imaging

Treatment (SX-682, pembrolizumab)

Eligibility Criteria

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

You may qualify if:

• Subjects aged 18 years and older
• Pathologically or cytologically confirmed non-small cell lung cancer with no known oncogenic EGFR mutation, ALK rearrangement, ROS1 rearrangement or RET rearrangement
• Tumoral PD-L1 expression \>=1% by any Clinical Laboratory Improvement Act (CLIA)-certified assay
• Metastatic or recurrent non-small cell lung cancer (NSCLC). Stage IIIC per 8th edition TNM stage classification is allowed if not amenable to curative surgery or radiation per investigator judgment
• At least one site of measurable disease as determined by the Investigator, using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1. Subjects must have ECOG PS 0 or 1 at the time of informed consent and at the time of treatment initiation
• Must be willing to provide pre-treatment archived specimen or undergo a biopsy procedure if archived specimen is not available
• Must be willing to provide an on-treatment biopsy, if deemed safe by the treating physician
• Platelet count \>= 100,000/uL
• Absolute neutrophil count \>= 1,500/uL
• Hemoglobin \>= 8g/dL
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\< 2.5 times upper limit of normal
• Creatinine =\< 2.0 mg/dL
• Women of child-bearing potential and sexually active men must agree to use adequate contraception (hormonal or barrier method) prior to treatment initiation, during treatment and for three months after completing treatment
• Negative beta-human chorionic gonadotropin (hCG) pregnancy test at screening for patients of childbearing potential. Pregnant or breast feeding women are not eligible

You may not qualify if:

• Participants must not have received prior chemotherapy or immune checkpoint inhibitor or immune-modulatory therapy (e.g. anti-PD\[L\]1, anti-CTLA4, anti-TIM3, anti-GITR, anti-TIGIT, anti-LAG3), for metastatic or recurrent NSCLC, with the following exceptions:
• Participants may have received prior chemotherapy, immune checkpoint inhibitor, and/or immune modulatory therapy in the curative setting if the last dose of treatment was more than (\>) 24 weeks prior to consenting
• For patients with NSCLC harboring an oncogenic alteration other than listed may have received prior small molecule inhibitor therapy (e.g. MET inhibitor for MET exon 14 mutated NSCLC). A wash-out period of at least 5 half-lives is required prior to start of study treatment
• Presence of other active cancers within the last 2 years. Patients with any prior early stage cancer who have received definitive local treatment at least 2 years previously and no evidence of recurrence are eligible. All patients with previously treated in situ carcinoma are eligible, as patients with history of non-melanoma skin cancer
• Symptomatic central nervous system (CNS) metastases; participants with known brain metastasis must be asymptomatic with no steroids or escalating doses of antiepileptics within 7 days prior to start of study treatment
• Patients with untreated CNS metastases may be enrolled as long as they meet the above criteria. Patients with bulky CNS metastases should consider receiving radiation prior to study entry per investigator judgment
• Participants with spinal cord compression must have received local treatment and must have been symptomatically stable with no use of steroids for at least 7 days prior to start of study treatment
• Participants must not have an active autoimmune disease that has required immune modulating treatment within (\<) 365 days prior to consenting (i.e., disease modifying agents, corticosteroids). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is allowed
• Inability to discontinue systemic corticosteroid therapy; systemic steroids must be tapered off 7 days prior to first dose of SX-682
• Known history of primary immunodeficiency
• History of organ transplant that requires use of immunosuppressives
• Current symptomatic pneumonitis and any past history of immune checkpoint inhibitor related pneumonitis regardless of steroid treatment history
• History of non-infectious pneumonitis (e.g. radiation pneumonitis) that required steroids within 3 months of start of study treatment
• Radiotherapy within 7 days of start of study treatment
• Major surgery within 21 days of start of study treatment. Minor surgery within 2 weeks of start of study treatment. Placement of vascular access device and biopsies are not considered major or minor surgery and are allowed

Sponsors & Collaborators

• University of Washington: lead
• National Cancer Institute (NCI): collaborator
• Syntrix Biosystems, Inc.: collaborator

Study Sites (1)

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Lung Neoplasms

Interventions

Biopsy; Specimen Handling; Magnetic Resonance Spectroscopy; pembrolizumab

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques; Spectrum Analysis; Chemistry Techniques, Analytical

Study Officials

• Christina S. Baik

  Fred Hutch/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Rebecca Wood

CONTACT

206-606-6970; rwood1@fredhutch.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 4, 2022
• First Posted: October 7, 2022
• Study Start: April 6, 2023
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): July 1, 2028
• Last Updated: December 4, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)