Reduced-dose Carboplatin-doublet-chemotherapy + Cemiplimab vs Cemiplimab Monotherapy in Treatment Naive Older and Frail Patients With Metastatic NSCLC With PD-L1 <50%

NCT07020065 | Recruiting Phase 2 DMC

• 1 other identifier: SAKK 18/24
• Study Type: interventional
• Target: 156
• Locations: 1 country
• Sites: 17

Brief Summary

Metastatic non-small cell lung cancer is often treated with a combination of chemotherapy and immunotherapy. In patients over the age of 70, some are already in poor health and frail, requiring assistance with daily activities, for example. Older and/or frail individuals often do not tolerate standard-dose chemotherapy well, and their risk of side effects is higher than that of younger patients. For this reason, the SAKK 18/24 study is investigating how effective and safe chemotherapy is in patients over 70 years of age when the chemotherapy drugs are administered at lower doses than usual. The aim of the study is to find a potentially effective and well-tolerated treatment for older people with metastatic non-small cell lung cancer.

Conditions

Metastatic NSCLC - Non-Small Cell Lung Cancer

Keywords

Reduced-dose chemotherapy; Cemiplimab; carboplatin; metastatic NSCLC; PD-L1 <50%; Non-Small Cell Lung Cancer; older and frail patients; phase II

Outcome Measures

Primary Outcomes (1)

• Progression-free survival (PFS)

  PFS is defined as time from randomization to confirmed tumor progression according to RECIST 1.1 or death due to any cause. Patients not experiencing an event will be censored at their last tumor assessment before starting a new anti-cancer treatment line (if any).

  From the date of randomization until the date of confirmed tumor progression according to RECIST 1.1 or death from any cause, assessed up to 1 year after end of treatment.

Secondary Outcomes (2)

• Overall survival (OS)

  From the date of randomization until the date of death from any cause, assessed up to 1 year after end of treatment.

• Objective response rate (ORR)

  From the date of randomization until the end of treatment, estimated up to 1 year after randomization.

Study Arms (2)

Experimental arm

EXPERIMENTAL

Non-squamous histology: * carboplatin IV AUC 3 day 1 * pemetrexed IV 300 mg/m2 day 1 * cemiplimab IV 350 mg, day 1 Every 3 weeks, for 4 cycles, followed by maintenance treatment with cemiplimab with or without pemetrexed (at same dose and interval as above). Squamous histology: * carboplatin IV AUC 1.5 day 1, d8 * gemcitabine IV 600 mg/m2 day 1, d8 * cemiplimab IV 350 mg, day 1 Every 3 weeks, for 4 cycles, followed by maintenance treatment with cemiplimab (350 mg q3w) Any histology: * carboplatin IV AUC 1.5 day 1, d8 * paclitaxel IV 50 mg/m2 day 1, d8 * cemiplimab IV 350 mg, day 1 Every 3 weeks, for 4 cycles, followed by maintenance treatment with cemiplimab (350 mg q3w)

Drug: Cemiplimab; Drug: Carboplatin; Drug: Pemetrexed & Gemcitabine; Drug: Paclitaxel

Comparator arm

ACTIVE COMPARATOR

cemiplimab IV 350 mg, day 1 Every 3 weeks (max. 2 years)

Drug: Cemiplimab

Interventions

Carboplatin DRUG

carboplatin IV AUC 3 day 1

Experimental arm

Paclitaxel DRUG

paclitaxel IV 50 mg/m2 day 1, d8

Experimental arm

Cemiplimab DRUG

cemiplimab IV 350 mg, day 1

Comparator arm; Experimental arm

Pemetrexed & Gemcitabine DRUG

pemetrexed IV 300 mg/m2 day 1 gemcitabine IV 600 mg/m2 day 1, d8

Experimental arm

Eligibility Criteria

• Age: 70 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• Informed Consent as documented by signature
• Histologically or cytologically confirmed NSCLC. Mixed histology with small-cell component is not allowed.
• Metastatic or advanced or recurrent NSCLC without a curative-intent treatment option (surgery or chemo-radiotherapy).
• PD-L1 \<50% by local testing (SP 142 excluded)
• ≥70 years
• ECOG 0-2
• G8 screening score of ≤14 and/or ineligible for full-dose chemotherapy, defined as doses of carboplatin AUC 5, pemetrexed 500 mg/m2, paclitaxel 175 mg/m2, gemcitabine 1200 mg/m2 (as per Investigator)
• Life expectancy ≥6 months
• Patients with a prior malignancy (except NSCLC, see EC 7.2.2 and 7.2.3) and treated with curative intent are eligible if all treatment of that malignancy was completed at least 2 years before registration and the patient has no evidence of disease at registration. Less than 2 years is acceptable for malignancies with low risk of recurrence and/or no late recurrence, after consultation with CI.
• Patients with asymptomatic untreated or symptomatic treated CNS metastases are eligible if corticosteroid dose \<10 mg prednisolone equivalent/day for at least 7 days
• Patients must be suitable to receive reduced-dose carboplatin-doublet chemotherapy in combination with immunotherapy including adequate bone marrow, renal and hepatic function as follows:
• Hemoglobin ≥90 g/L, neutrophils ≥1.5 G/L, Thrombocytes ≥100G/L
• Creatinine clearance (Cockroft-Gault) ≥30 mL/min
• ASAT/ALAT ≤2xULN, Bilirubin ≤1.5xULN (≤3xULN for patients with Gilbert's disease),
• Men agree not to donate sperm or father a child during trial treatment and until 6 months after the last dose of trial treatment

You may not qualify if:

• Actionable genomic alteration for 1L treatment (EGFR, ALK, ROS1, RET, NTRK, MET Exon14 skipping). Testing is required for any NSQ-NSCLC or patients with SCC and a smoking history of ≤10py.
• Prior systemic treatment for metastatic NSCLC.
• Prior chemotherapy and/or immunotherapy in curative-intent treatment for locally advanced NSCLC in the past 6 months.
• Oligometastatic treatment concept with induction systemic therapy and planned LAT to all lesions.
• High tumor burden with a risk of rapid critical progression, as judged by the Investigator. Careful patient selection is important in order to prevent that patients in the comparator arm are not eligible for receiving add-on reduced-dose chemotherapy anymore if primary progression occurs (e.g., pericardial infiltration, high liver metastasis load etc).
• Active, treatment-requiring auto-immune disease in the past 2 years other than vitiligo, alopecia, hypothyroidism, type 1 diabetes or diet-controlled celiac disease.
• History of pneumonitis in the past 5 years.
• Systemic corticosteroid treatment ≥10 mg/day of prednisolone-equivalent or any other systemic immunosuppressive medication within 7 days prior to first dose of study intervention (except as needed for chemotherapy premedication or for physiologic corticosteroid replacement)
• Any infection requiring hospitalization or treatment with IV anti-infectives within 2 weeks of first dose of study medication
• Uncontrolled infection with HIV, hepatitis B or hepatitis C infection
• Receipt of a live vaccine within 4 weeks of start of study medication
• Receipt of COVID-19 vaccination within 1 week of planned start of study medication or for which the planned COVID-19 vaccinations would not be completed 1 week prior to start of study medication
• Organ transplant

Sponsors & Collaborators

• Swiss Cancer Institute: lead

Study Sites (17)

HFR Fribourg

Fribourg, Villars-sur-Glâne, 1752, Switzerland

RECRUITING

Kantonsspital Aarau

Aarau, CH-5001, Switzerland

RECRUITING

Kantonsspital Baden

Baden, 5404, Switzerland

RECRUITING

Universitätsspital Basel

Basel, 4031, Switzerland

RECRUITING

Inselspital

Bern, 3010, Switzerland

RECRUITING

Kantonsspital Baselland

Bruderholz, 4101, Switzerland

RECRUITING

Kantonsspital Graubuenden

Chur, CH-7000, Switzerland

RECRUITING

Spital Thurgau AG - Kantonsspital Frauenfeld

Frauenfeld, 8501, Switzerland

RECRUITING

Hôpitaux Universitaires de Genève

Geneva, 1211, Switzerland

RECRUITING

Kantonsspital Olten - Solothurner Spitäler

Olten, 4600, Switzerland

RECRUITING

Kantonsspital - St. Gallen

Sankt Gallen, CH-9007, Switzerland

RECRUITING

Hôpital du Valais - Sion

Sion, 1951, Switzerland

RECRUITING

Spital Thun

Thun, 3600, Switzerland

RECRUITING

EOC Istituto Oncologico della Svizzera Italiana (IOSI)

Viganello, 6962, Switzerland

RECRUITING

Kantonsspital Winterthur

Winterthur, 8401, Switzerland

RECRUITING

KSW Kantonsspital Winterthur

Winterthur, 8401, Switzerland

RECRUITING

Stadtspital Zürich Triemli

Zurich, 8063, Switzerland

RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

cemiplimab; Carboplatin; Pemetrexed; Gemcitabine; Paclitaxel

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes

Study Officials

• Laetitia Mauti, MD

  Kantonsspital Winterthur KSW

  STUDY CHAIR

Central Study Contacts

Gisela Müller

CONTACT

+41 31 389 91 91; trials@swisscancerinstitute.ch

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: A multicenter randomized open-label phase II trial, with parallel design.

Study Record Dates

• First Submitted: June 5, 2025
• First Posted: June 13, 2025
• Study Start: April 10, 2026
• Primary Completion (Estimated): September 1, 2028
• Study Completion (Estimated): September 1, 2030
• Last Updated: April 15, 2026

Record last verified: 2026-04

Locations

CH (17)