Using pembrolizumab and chemotherapy for early-stage non-small cell lung cancer

Single Cell Analysis of CXCL13+PD1+ CD8 T Cell in Association With Resistance to Pembrolizumab and Chemotherapy Neoadjuvant/Adjuvant of NSCLC

This study is testing whether combining a new immune therapy called pembrolizumab with chemotherapy can help people with early-stage non-small cell lung cancer before and after surgery.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 70 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Peking University (other)
• Drugs / interventions: pembrolizumab, chemotherapy, radiation, prednisone, immunotherapy
• Locations: 2 sites (Beijing, Beijing and 1 other locations)
• Trial ID: NCT05894889 on ClinicalTrials.gov

What this trial studies

This study evaluates the efficacy and safety of combining neoadjuvant pembrolizumab with chemotherapy, followed by adjuvant pembrolizumab in patients with resectable stage IIA-IIIB non-small cell lung cancer (NSCLC) without sensitizing EGFR/ALK mutations. The research aims to understand the role of specific immune cells (CXCL13+PD1+ CD8 T cells) in relation to treatment response and resistance. Participants will receive pembrolizumab via IV infusion, and their pathological responses will be analyzed post-treatment. The study builds on previous findings that suggest immunotherapy may improve surgical outcomes for locally advanced NSCLC.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with histologically confirmed resectable stage IIA-III(N2) NSCLC without sensitizing EGFR/ALK mutations.

Not a fit: Patients with non-resectable tumors or those with sensitizing EGFR/ALK mutations may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could significantly improve treatment outcomes and reduce recurrence rates in patients with early-stage NSCLC.

How similar studies have performed: Previous studies, such as KEYNOTE-671 and KEYNOTE-091, have shown positive results with similar immunotherapy approaches, indicating potential for success.

Eligibility criteria

Inclusion Criteria:

1. Male/female participants who are at least 18 years of age on the day of signing informed consent with histologically confirmed diagnosis of \[Stage II, IIIA or IIIB(N2) NSCLC (AJCC Version 8)\] will be enrolled in this study.

   Note: mixed cellularity tumors are allowed. tumor should be considered resectable in terms of surgeon's determinations before study entry by investigators. Lymph nodes disease are recommended to have pathological confirmation. A PET-CT may be utilized as a surrogate for pathologic staging by site's feasibility.
2. Male participants:

   A male participant must agree to use a contraception as detailed in Appendix 3 of this protocol during the treatment period and for at least 1 year after the last dose of study treatment and refrain from donating sperm during this period.
3. Female participants:

   A female participant is eligible to participate if she is not pregnant (see Appendix 3), not breastfeeding, and at least one of the following conditions applies:
   1. Not a woman of childbearing potential (WOCBP) as defined in Appendix 3 OR
   2. A WOCBP who agrees to follow the contraceptive guidance in Appendix 3 during the treatment period and for at least \[180 days after the last dose of carboplatin and for at least 120 days after the last dose of pembrolizumab, whichever occurs latest\].
4. The participant (or legally acceptable representative if applicable) provides written informed consent for the trial and may also provide consent for future biomedical research.
5. Have measurable disease based on RECIST 1.1. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions. Participants suspected with secondary lung cancer (eg. ground glass nodules) were also eligible for this study (For solid nodules, biopsy, if available, should be performed in case of any intrapulmonary metastasis).
6. Archival tumor tissue sample or newly obtained \[core, incisional or excisional\] biopsy of a tumor lesion not previously irradiated has been provided. Formalin-fixed, paraffin embedded (FFPE) tissue blocks are preferred to slides. Newly obtained biopsies are preferred to archived tissue.
7. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. Evaluation of ECOG is to be performed within 7 days prior to the first dose of study intervention.
8. Have adequate organ function as defined in the following table. Specimens must be collected within 10 days prior to the start of study intervention.

Exclusion Criteria:

1. Have confirmed sensitizing EGFR mutation or ALK alterations. Note: EGFR and ALK testing will be performed in local hospital, and do not need to be sent to the central laboratory.
2. A WOCBP who has a positive urine pregnancy test within 72 hours prior to treatment (see Appendix 3). If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.

   Note: in the event that 72 hours have elapsed between the screening pregnancy test and the first dose of study treatment, another pregnancy test (urine or serum) must be performed and must be negative in order for subject to start receiving study medication.
3. Has one of the following tumor locations/types:

   * NSCLC involving the superior sulcus
   * Large cell neuro-endocrine cancer
   * Sarcomatoid tumor
4. Has had an allogenic tissue/solid organ transplant.
5. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX 40, CD137).
6. Has received prior systemic anti-cancer therapy including investigational agents for the current malignancy prior to \[allocation\].
7. Has received prior radiotherapy within 2 weeks of start of study intervention or radiation-related toxicities requiring corticosteroids.
8. Has received a live vaccine or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines is allowed.

   Note: please refer to Section 5.5.2 for information on COVID-19 vaccines
9. Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration.
10. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
11. Known additional malignancy that is progressing or has required active treatment within the past 5 years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin or carcinoma in situ, excluding carcinoma in situ of the bladder, that have undergone potentially curative therapy are not excluded.
12. Has a known severe hypersensitivity (≥Grade 3) to any of the study chemotherapy agents and/or to any of their excipients.
13. Has active autoimmune disease that has required systemic treatment in the past 2 years except replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid)
14. Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
15. Has an active infection requiring systemic therapy.
16. Has a known history of Human Immunodeficiency Virus (HIV) infection. Note: No HIV testing is required unless mandated by local health authority.
17. Concurrent active Hepatitis B (defined as HBsAg positive and/or detectable HBV DNA) and Hepatitis C virus (defined as anti-HCV Ab positive and detectable HCV RNA) infection.

    Note: Hepatitis B and C screening tests are not required unless:
    * Known history of HBV and HCV infection
    * As mandated by local health authority
18. Has a history or current evidence of any condition, therapy, or laboratory abnormality or other circumstance that might confound the results of the study, interfere with the participant's participation for the full duration of the study, such that it is not in the best interest of the participant to participate, in the opinion of the treating investigator.
19. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
20. Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of trial treatment.
21. Participants who have had major surgery within 14 days of first treatment.

Where this trial is running

Beijing, Beijing and 1 other locations

• Peking University — Beijing, Beijing, China (RECRUITING)
• Shanghai Pulmonary Hospital — Shanghai, Shanghai, China (RECRUITING)

Study contacts

• Study coordinator: Zemin Zhang, PhD

Conditions: Stage IIIB Non-small Cell Lung Cancer, Stage IIA Non-small Cell Lung Cancer, Stage IIB Non-small Cell Lung Cancer, Stage IIIA Non-small Cell Lung Cancer, Early stage NSCLC, neoadjuvant, adjuvant, pembrolizumab