Understanding resistance to chemo-immunotherapy in aggressive lung cancers

A Prospective Observational Study on Genomic and Methylation Signatures in Patients with Extensive-Stage Small Cell Lung Cancer and Metastatic Large Cell Neuroendocrine Carcinoma Undergoing Chemo-Immunotherapy

This study is trying to understand why some adults with aggressive lung cancers don’t respond to chemo-immunotherapy, so they can find better treatment options for these patients.

Quick facts

• Study type: Observational
• Enrollment: 111 (estimated)
• Ages: 18 Years to 85 Years
• Sex: All
• Sponsor: Oncology Center of Biochemical Education And Research (other)
• Drugs / interventions: atezolizumab, durvalumab, chemotherapy, immunotherapy, prednisone
• Locations: 2 sites (New York, New York and 1 other locations)
• Trial ID: NCT06717243 on ClinicalTrials.gov

What this trial studies

This observational study aims to investigate the genomic and epigenetic factors that contribute to resistance against chemo-immunotherapy in adults with extensive-stage small cell lung cancer (ES-SCLC) and metastatic large cell neuroendocrine carcinoma (LCNEC). By analyzing biomarkers such as circulating tumor cells (CTCs) and tumor DNA (ctDNA), the study seeks to uncover the molecular mechanisms driving treatment resistance. The findings could lead to more personalized and effective treatment strategies for these aggressive cancers, which currently have limited options and poor prognoses.

Who should consider this trial

Good fit: Ideal candidates for this study are adults aged 18-85 with newly diagnosed extensive-stage small cell lung cancer or metastatic large cell neuroendocrine carcinoma who are initiating standard-of-care chemo-immunotherapy.

Not a fit: Patients who have previously received systemic therapy for ES-SCLC or LCNEC may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide insights that lead to more effective and personalized treatment options for patients with ES-SCLC and LCNEC.

How similar studies have performed: Other studies have shown promise in identifying biomarkers for treatment resistance in similar cancers, suggesting that this approach may yield valuable insights.

Eligibility criteria

Inclusion Criteria:

* Age: Adults aged 18-85 years.
* Histologically confirmed locally advanced extensive-stage small cell lung cancer (ES-SCLC).
* Histologically confirmed locally advanced or metastatic large cell neuroendocrine carcinoma (LCNEC).
* Treatment Plan: Eligible patients must be initiating standard-of-care chemo-immunotherapy, including platinum-based chemotherapy (cisplatin or carboplatin) combined with immune checkpoint inhibitors (atezolizumab or durvalumab).
* Measurable Disease: At least one measurable or evaluable lesion as defined by RECIST 1.1 criteria.
* Baseline Biospecimen Availability: Patients must agree to provide baseline blood and tumor biopsy samples for molecular and genomic analyses.
* Treatment Naïve for Study Indication: Patients should not have received prior systemic therapy for ES-SCLC or LCNEC.
* Life Expectancy: Estimated life expectancy of at least 3 months, as determined by the treating physician.
* Follow-Up Commitment: Willingness to attend scheduled follow-up visits and provide additional biospecimens (blood and/or tissue) during treatment and at progression.
* Performance Status: ECOG performance status of 0-2.
* Organ Function: Adequate hematologic, renal, and hepatic function as per the treating physician's discretion.
* Consent: Ability and willingness to provide written informed consent for participation in the study and collection of biospecimens (e.g., blood and tumor tissue).
* Compliance with Study Protocol: Demonstrated ability and willingness to comply with all study-related procedures, including biospecimen collection and follow-up visits.
* Non-Pregnant and Non-Lactating: Women of childbearing potential must have a negative pregnancy test at baseline and agree to use effective contraception during the study period.
* Immunotherapy Eligibility: Patients must not have contraindications to immune checkpoint inhibitors (e.g., autoimmune diseases requiring systemic immunosuppressive therapy).
* Platinum-Based Therapy Tolerance: Patients must be deemed medically fit to receive platinum-based chemotherapy (cisplatin or carboplatin) as determined by the treating physician.
* No Active Infections: Patients must not have active, uncontrolled infections, including but not limited to tuberculosis, hepatitis B, hepatitis C, or HIV.
* Psychosocial Stability: Patients must have adequate psychosocial support and the mental capacity to understand and provide informed consent for participation in the study.
* Stable Brain Metastases: Patients with brain metastases are eligible if the metastases have been treated (e.g., surgery or radiotherapy) and are stable for at least 4 weeks prior to enrollment, as confirmed by imaging.
* Steroid Use for Brain Metastases: Patients requiring corticosteroids for brain metastases are eligible only if they are on a stable or tapering dose equivalent to ≤10 mg/day of prednisone for at least 2 weeks prior to enrollment.

Exclusion Criteria:

* Uncontrolled Brain Metastases: Patients with untreated or progressive brain metastases causing significant neurological symptoms.
* Concurrent Malignancies: Presence of any active malignancy other than ES-SCLC or LCNEC within the past 3 years, except for treated non-melanoma skin cancer or in situ cervical carcinoma.
* Previous Systemic Therapy: Prior systemic chemotherapy or immunotherapy for ES-SCLC or LCNEC.
* Severe Comorbidities: Significant comorbidities, such as uncontrolled cardiovascular, respiratory, or autoimmune diseases, that could interfere with study participation or treatment.
* Active Infection: Patients with active infections requiring systemic therapy, including tuberculosis, hepatitis B or C, or HIV.
* Pregnancy or Lactation: Pregnant or lactating women, or women of childbearing potential who are not using effective contraception.
* Immunosuppressive Therapy: Patients requiring systemic immunosuppressive therapy, including high-dose corticosteroids (equivalent to \>10 mg/day prednisone), within 2 weeks prior to enrollment.
* Severe Allergic Reactions: History of severe hypersensitivity reactions to any component of the planned treatment regimen, including platinum-based chemotherapy or immune checkpoint inhibitors.
* Life-Threatening Conditions: Life expectancy less than 3 months, as assessed by the treating physician.
* Inability to Comply: Patients unable or unwilling to adhere to study protocols, including biospecimen collection and follow-up visits.

Where this trial is running

New York, New York and 1 other locations

• Icahn School of Medicine at Mount Sinai — New York, New York, United States (NOT_YET_RECRUITING)
• 3rd Department of Medicine, National and Kapodistrian University of Athens, Sotiria Hospital — Athens, Greece (RECRUITING)

Conditions: Small Cell Lung Cancer, Large Cell Neuroendocrine Tumors, Treatment Failure, Biomarkers / Blood, Biomarkers, Immunotherapy, Large Cell Neuroendocrine Carcinoma, Chemo-Immunotherapy