SX-682 + Pembrolizumab for Lung Cancer

Overseen By Rebecca Wood

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Washington

Must not be taking: Immune checkpoint inhibitors

Disqualifiers: Active cancers, CNS metastases, autoimmune, others

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

Prior Safety Data This treatment has passed at least one previous human trial

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

Compensation: Varies

Number of Visits: 1

Duration: 24 months

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether combining two treatments, SX-682 and pembrolizumab, can more effectively treat non-small cell lung cancer that has spread or returned. SX-682 reduces inflammation and helps immune cells target cancer, while pembrolizumab (KEYTRUDA) boosts the immune system to attack tumors. The trial suits those with metastatic or recurrent non-small cell lung cancer who have not received prior treatments for these conditions. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering a chance to contribute to important findings.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop all current medications, but you must stop taking systemic corticosteroids at least 7 days before starting the trial. If you are on small molecule inhibitor therapy, a washout period (time without taking the medication) of at least 5 half-lives is required before starting the study treatment.

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

Research has shown that the combination of SX-682 and pembrolizumab is generally well-tolerated by patients. In one study, this combination proved safe for patients. Some patients responded positively, and the treatment effectively controlled the disease. While side effects can occur, they are usually manageable for most patients. The study found no serious safety issues, offering reassurance to those considering joining the trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of SX-682 and pembrolizumab for lung cancer because it targets the disease in a unique way. Unlike standard treatments that typically focus on blocking cancer cell growth, SX-682 works by inhibiting the CXCR1/2 chemokine receptors, which can help prevent the immune system from being suppressed by the tumor. This means it could potentially enhance the effectiveness of pembrolizumab, an existing immunotherapy that helps the immune system attack cancer cells. By combining these mechanisms, the treatment aims to offer a more comprehensive approach to fighting lung cancer, possibly leading to better outcomes for patients.

What evidence suggests that SX-682 and pembrolizumab might be effective for non-small cell lung cancer?

Research has shown that using SX-682 with pembrolizumab might help treat advanced or returning non-small cell lung cancer. In this trial, participants will receive the combination of SX-682 and pembrolizumab. One study found that this combination is generally safe, with patients showing positive responses and good control over the disease. SX-682 blocks signals that help cancer grow and spread, making it easier for the immune system to fight the cancer. Pembrolizumab aids the immune system by targeting a protein called PD-1 on immune cells. Together, these treatments might be more effective than using either one alone for this type of lung cancer. ^{1 2 4 6 7}

Who Is on the Research Team?

Christina S. Baik

Principal Investigator

Fred Hutch/University of Washington Cancer Consortium

Are You a Good Fit for This Trial?

This trial is for adults with stage IIIC or IV non-small cell lung cancer that's spread or come back, without certain genetic mutations. Participants need a specific blood platelet count, no recent serious infections, and must not have had prior treatments like chemotherapy for their metastatic disease. They should be in good physical condition (ECOG status 0 or 1), able to provide tissue samples, and use contraception if applicable.

Inclusion Criteria

My lung cancer has spread or come back and cannot be cured by surgery or radiation.

I agree to use birth control during and for three months after treatment.

I am willing to undergo a biopsy during treatment if my doctor says it's safe.

Exclusion Criteria

I have brain metastases but no symptoms, and I haven't taken steroids or antiepileptics in the last 7 days.

I do not have active hepatitis B, C, or tuberculosis, and haven't needed IV antibiotics in the last week.

I have received treatments like chemotherapy or immunotherapy for my cancer after it spread or came back.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive SX-682 orally twice daily and pembrolizumab intravenously every 3 weeks for up to 24 months

24 months

Bi-weekly visits for drug administration and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

60 months

Periodic visits for imaging and blood sample collection

What Are the Treatments Tested in This Trial?

Interventions

• Pembrolizumab
• SX-682

Trial Overview The trial tests SX-682 combined with pembrolizumab against advanced non-small cell lung cancer. SX-682 blocks signals that help tumors evade the immune system while pembrolizumab activates T-cells to attack cancer cells. The study aims to see if this combo is more effective than individual treatments.

How Is the Trial Designed?

Group I: Treatment (SX-682, pembrolizumab) Experimental Treatment 7 Interventions

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.

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?

University of Washington

Lead Sponsor

Trials

1,858

Recruited

2,023,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Syntrix Biosystems, Inc.

Industry Sponsor

Trials

14

Recruited

810+

Published Research Related to This Trial

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]

In a study of 24 patients with advanced non-small cell lung cancer (NSCLC) treated with pembrolizumab, the objective response rate was 45.8%, indicating that nearly half of the patients experienced a reduction in tumor size after treatment.

Pembrolizumab showed promising results even in PD-L1-negative patients, with a major pathological response of 75% and a pathological complete response of 50% in those who underwent surgery, suggesting its potential effectiveness across different patient profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of pembrolizumab for the treatment of advanced non-small cell lung cancer: a retrospective, single-centre, single-arm study. Guo, T., Ding, Y., Chen, L., 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]

Pembrolizumab is a safe and effective immune checkpoint inhibitor that targets the PD-1 receptor, currently approved for treating advanced melanoma and metastatic non-small cell lung cancer (NSCLC).

Ongoing studies are exploring the potential of pembrolizumab in combination with other treatments for lung cancer and other cancer types, while also investigating biomarkers that may predict patient response to this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of PD-L1 positive advanced or metastatic non-small cell lung cancer. Dang, TO., Ogunniyi, A., Barbee, MS., et al.[2020]

Pembrolizumab, a monoclonal antibody targeting PD-1, showed significant efficacy in treating a 79-year-old patient with advanced squamous cell lung cancer, leading to a complete response after just 3 cycles of treatment.

However, the patient developed acute myelomonocytic leukemia after starting pembrolizumab, highlighting a potential safety concern that warrants further investigation into the drug's effects on blood cell production.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute myelomonocytic leukemia during pembrolizumab treatment for non-small cell lung cancer: A case report. Kim, HB., Park, SG., Hong, R., et al.[2020]

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 Phase 2 study involving 35 patients with non-small cell lung cancer, neoadjuvant pembrolizumab was found to be safe and well tolerated, with only one surgery delay due to thyroiditis and no mortality within 90 days post-surgery.

The study showed a high rate of R0 resection (88%) and a major pathologic response in 28% of patients, indicating that pembrolizumab may be more effective than standard neoadjuvant chemotherapy in this setting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Perioperative outcomes of pulmonary resection after neoadjuvant pembrolizumab in patients with non-small cell lung cancer. Tong, BC., Gu, L., Wang, X., 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]

Pembrolizumab (KEYTRUDA) was approved by the FDA for treating advanced melanoma, showing an overall response rate of 24% in a trial of 89 patients, with 86% of responses lasting at least 6 months.

While there are potential immune-mediated side effects, the benefits of prolonged tumor response durations were deemed to outweigh these risks, marking an improvement over existing treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. Chuk, MK., Chang, JT., Theoret, MR., et al.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05570825

SX-682 With Pembrolizumab for the Treatment of ... 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 ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.9508

Safety and efficacy of first-in-class CXCR1/2 inhibitor SX ... SX-682 combined with pem had a tolerable safety profile and activity reflected by objective responses and clinically meaningful disease control.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6483637/

Inhibiting myeloid-derived suppressor cell trafficking ... In summary, this work demonstrated the ability of SX-682 to enhance responses to PD-axis immune checkpoint blockade and adoptive transfer of ...

4. cancer.gov cancer.gov/clinicaltrials/NCI-2019-01126

SX-682 Treatment in Subjects With Metastatic Melanoma ... The study will begin to determine if SX-682 is a safe and effective treatment of melanoma. It is thought that SX-682 will block MDSCs from going to the cancer, ...

5. fredhutch.org fredhutch.org/en/research/clinical-trials/trial-details.fh_trial_id_14585.sx-682-with-pembrolizumab-for-the-treatment-of-metastatic-or-recurrent-stage-iiic-or-iv-non-small-cell-lung-cancer.html

SX-682 With Pembrolizumab for the Treatment of ... 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.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT03161431

SX-682 Treatment in Subjects With Metastatic Melanoma ... This study will be the first study to begin to determine if the newly discovered drug SX-682 can block cancers from attracting MDSCs.

7. ascopubs.org ascopubs.org/doi/10.1200/JCO.2022.40.4_suppl.TPS631

A phase I study to evaluate the safety and tolerability of SX- ... We are currently conducting a Phase I study (NCT04477343) evaluating SX-682, an oral CXCR1/2 inhibitor, and Nivolumab as maintenance treatment for advanced ...