Clinical trial NCT06917573: PALACE: Cemiplimab Trial According to ctDNA Levels
Official title: 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
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
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
Keywords: Cemiplimab
ctDNA levels
Chemotherapy
Non-resectable non-small cell lung cancer
Lead sponsor: Fundación GECP
Sponsor class: OTHER
First posted: 2025-04-08
Enrollment: 63
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is an open-label, non-randomised, phase II, multicenter clinical trial. 63 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 will be enrolled in this trial to determine whether therapy decision making based on ctDNA analysis improves overall survival.

Detailed description: This is an open-label, non-randomised, phase II, multicenter clinical trial. The total sample size is 63 patients. The population to be included are 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 therap.

Patients will be treated with Cemiplimab for 2 cycles and after response evaluation and ctDNA levels analysis, patients will be treated with Cemiplimab plus chemotherapy or cemiplimab monotherapy depending on response and ctDNA levels.

The primary research goal is to determine whether therapy decision making based on ctDNA analysis improves overall survival.

Patient accrual is expected to be completed within 1.5 years excluding a run-in-period of 4-6 months. An estimated treatment period of 2 years, 2 years of follow-up and the preparation of the final report and the close out visit are expected to extend the study duration to a total of 6.5 years.

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.

Primary outcomes:
measure: To determine whether therapy decision making based on ctDNA analysis improves overall survival
timeFrame: From the date of the end of two cycles of Cemiplimab treatment until 24 months
Secondary outcomes:
measure: To assess the efficacy of the treatment in terms of the Progression Free Survival (PFS) at 12 months
timeFrame: From the date of the end of treatment until 12 months
measure: To evaluate the sites of first failure
timeFrame: From the date of the end of treatment until the date of last follow up, assessed up to 24 months
measure: Duration of response (DOR)
timeFrame: From date of documentation of tumor response until date of first documented progression, assessed up to 24 months
Other outcomes:
Locations:
city: Elche
country: Spain
facility: Hospital General de Elche
state: Alicante
city: Badalona
country: Spain
facility: ICO Badalona, Hospital Germans Trias i Pujol
state: Barcelona
city: Hospitalet de Llobregat
country: Spain
facility: ICO Hospitalet
state: Barcelona
city: Jerez De La Frontera
country: Spain
facility: Hospital Universitario Jerez De La Frontera
state: Cádiz
city: A Coruña
country: Spain
facility: Hospitalario Universitario A Coruña
state: La Coruña
city: Las Palmas De Gran Canaria
country: Spain
facility: Hospital Universitario Dr. Negrín
state: Las Palmas
city: Leganés
country: Spain
facility: Hospital Universitario Severo Ochoa
state: Madrid
city: Palma De Mallorca
country: Spain
facility: Hospital Universitario Son Espases
state: Mallorca
city: Alicante
country: Spain
facility: Hospital General de Alicante
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d' Hebron
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
city: Bilbao
country: Spain
facility: Hospital De Basurto
city: Girona
country: Spain
facility: Hospital Dr. Josep Trueta
city: Madrid
country: Spain
facility: Hospital Clínico San Carlos
city: Madrid
country: Spain
facility: Hospital Universitario Fundación Jiménez Díaz
city: Madrid
country: Spain
facility: Hospital Puerta de Hierro
city: Málaga
country: Spain
facility: Hospital Universitario Regional de Málaga
city: Palma De Mallorca
country: Spain
facility: Hospital Universitari Son Llatzer
city: Salamanca
country: Spain
facility: Hospital Universitario Salamanca
city: Valencia
country: Spain
facility: Hospital General de Valencia
Study officials:
affiliation: Fundación GECP President
name: Mariano Provencio, MD
role: STUDY_CHAIR
References: