Cemiplimab guided by ctDNA levels (PALACE)

Phase II Clinical Trial With an Adaptive Design According to Response to Cemiplimab Monotherapy Using ctDNA and Subsequent Treatment With Chemotherapy (CT) and Cemiplimab or Cemiplimab Monotherapy in First Line Advanced NSCLC Patients

This study will see if starting adults with advanced (stage IIIB/C or IV) non-small cell lung cancer and PD-L1 ≥50% on cemiplimab, then using ctDNA and early scans to decide whether to add chemotherapy, can improve overall survival.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 63 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Fundación GECP (Academic / other)
• Drugs / interventions: cemiplimab, chemotherapy
• Locations: 20 sites (Alicante, Alicante and 19 other locations)
• Trial ID: NCT06917573 on ClinicalTrials.gov

What this trial studies

This is an open-label, non-randomised, multicenter phase II trial enrolling 63 patients with stage IV or stage IIIB/C non-small cell lung cancer who have not received prior systemic therapy. All participants receive two cycles of cemiplimab, then have response assessment and ctDNA testing to guide whether they continue cemiplimab alone or add chemotherapy (carboplatin plus paclitaxel). The primary aim is to see whether using ctDNA to drive therapy decisions improves overall survival. The study includes about 2 years of treatment and 2 years of follow-up, conducted at several hospitals in Spain.

Who should consider this trial

Good fit: Adults (≥18 years) with histologically confirmed stage IV or stage IIIB/C NSCLC (per 8th edition TNM), PD-L1 ≥50%, ECOG 0-1, no prior systemic anti-cancer therapy, and at least one measurable lesion are ideal candidates.

Not a fit: Patients with PD-L1 <50%, prior systemic therapy, poor performance status (ECOG >1), resectable disease, or who cannot provide ctDNA samples or attend the Spanish sites are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, this approach could help doctors tailor treatment so some patients avoid unnecessary chemotherapy while others receive earlier combination therapy, potentially improving survival.

How similar studies have performed: PD-1/PD-L1 inhibitors have shown clear benefit in high PD-L1 NSCLC, but using ctDNA to guide adding chemotherapy is a relatively new strategy with limited evidence so far.

Eligibility criteria

Inclusion Criteria:

* Histologically confirmed stage IV or stage IIIB/C not candidates for definitive chemo/radiotherapy or surgical resection non-small cell lung cancer (NSCLC) per the 8th edition TNM with no prior systemic anti-cancer therapy
* PDL1 ≥50%
* ECOG performance status 0-1
* Patients aged ≥ 18 years
* Prior adjuvant or neoadjuvant chemotherapy for early stage is permitted if completed at least 6 months prior to enrolment
* Presence of at least one measurable lesion by CT-scan per RECIST version 1.1
* Anticipated life expectancy \>12 weeks
* Correct hematological, hepatic and renal function
* Patient consent must be obtained in the appropriate manner as established in the applicable local and regulatory requirements
* Patients must be accessible for treatment and follow-up
* Women of childbearing potential, including women who had their last menstrual period in the last 2 years, must have a negative serum or urine pregnancy test within 3 days before enrolment.
* All sexually active men and women of childbearing potential must use a highly effective contraceptive method during the study treatment and for a period of at least 4 months following the last administration of trial drugs

Exclusion Criteria:

* Patients whose tumors harbor an activating mutation in EGFR, ALK translocation, or ROS Proto-Oncogene 1 (ROS1) rearrangements sensitive to available targeted inhibitor therapy
* Patients with grade ≥2 neuropathy
* Pregnant or breastfeeding women
* Patients with a weight loss \>10% within the previous 3 months
* Patients with carcinomatous meningitis
* Patients with a history of other malignant diseases within the past 3 years
* Patients must have recovered from a major surgery at least 14 days prior to enrolment
* Patients with active or uncontrolled infections or with serious medical conditions or disorders that may not allow patient management as established in the protocol
* Prior treatment with antineoplasic drugs or thoracic radiotherapy for any reason different from the ones specific in the inclusion criteria
* Patients who have received prior neo-adjuvant, adjuvant chemotherapy, radiotherapy, or chemo-radiotherapy with curative intent for non-metastatic disease less than 6 months before enrollment since the last chemotherapy, radiotherapy, or chemo-radiotherapy
* Patients with a combination of small cell lung cancer and non-small cell lung cancer, a carcinoid lung tumor or large cell neuroendocrine carcinoma
* Has known allergy or hypersensitivity to components of study drug
* Significant comorbidities that preclude the administration of chemotherapy according to the investigator's criteria
* Ongoing or recent evidence of significant autoimmune disease that required treatment with systemic immunosuppressive treatments
* Untreated brain metastasis(es) that may be considered active
* Immunosuppressive corticosteroid doses within 4 weeks prior to the first dose of cemiplimab
* Uncontrolled infection with hepatitis B or hepatitis C or human immunodeficiency virus; or diagnosis of immunodeficiency
* History of interstitial lung disease or active, noninfectious pneumonitis that required immune-suppressive doses of glucocorticoids to assist with management.
* History of documented allergic reactions or acute hypersensitivity reactions attributed to antibody treatments
* Patients with a history of solid organ transplant
* Receipt of live vaccines within 30 days of first study treatment
* Women of childbearing potential, or sexually active men, who are unwilling to practice highly effective contraception prior to the initial dose/start of the first treatment prior to the start of the first treatment, during the study, and for at least 4 months after the last dose.

Where this trial is running

Alicante, Alicante and 19 other locations

• Hospital General de Alicante — Alicante, Alicante, Spain (Recruiting)
• Hospital General de Elche — Elche, Alicante, Spain (Recruiting)
• ICO Badalona, Hospital Germans Trias i Pujol — Badalona, Barcelona, Spain (Recruiting)
• Hospital Universitari Vall d' Hebron — Barcelona, Barcelona, Spain (Recruiting)
• Hospital de la Santa Creu i Sant Pau — Barcelona, Barcelona, Spain (Recruiting)
• ICO Hospitalet — L'Hospitalet de Llobregat, Barcelona, Spain (Recruiting)
• Hospital De Basurto — Bilbao, Bilbao, Spain (Recruiting)
• Hospital Universitario Jerez De La Frontera — Jerez de la Frontera, Cádiz, Spain (Not_yet_recruiting)
• Hospital Dr. Josep Trueta — Girona, Girona, Spain (Recruiting)
• Hospitalario Universitario A Coruña — A Coruña, La Coruña, Spain (Recruiting)
• Hospital Universitario Dr. Negrín — Las Palmas de Gran Canaria, Las Palmas, Spain (Recruiting)
• Hospital Universitario Severo Ochoa — Leganés, Madrid, Spain (Recruiting)
• Hospital Clínico San Carlos — Madrid, Madrid, Spain (Recruiting)
• Hospital Universitario Fundación Jiménez Díaz — Madrid, Madrid, Spain (Recruiting)
• Hospital Puerta de Hierro — Madrid, Madrid, Spain (Recruiting)
• Hospital Universitario Son Espases — Palma de Mallorca, Mallorca, Spain (Recruiting)
• Hospital Universitario Regional de Málaga — Málaga, Málaga, Spain (Recruiting)
• Hospital Universitari Son Llatzer — Palma de Mallorca, Palma de Mallorca, Spain (Recruiting)
• Hospital Universitario Salamanca — Salamanca, Salamanca, Spain (Recruiting)
• Hospital General de Valencia — Valencia, Valencia, Spain (Recruiting)

Study contacts

• Study coordinator: Eva Pereira

Conditions Non Small Cell Lung Cancer Metastatic; Lung Diseases; Stage IV Non-small Cell Lung Cancer; Stage III Non-small Cell Lung Cancer; Respiratory Tract Neoplasms; Thoracic Neoplasms; Cemiplimab; ctDNA levels