Reduced-dose Carboplatin-doublet-chemotherapy + Cemiplimab vs Cemiplimab Monotherapy in Treatment Naive Older and Frail Patients With Metastatic NSCLC With PD-L1 <50% A Multicentre Randomized Open-label Phase II Trial

Plain English Summary

Reduced-dose Carboplatin-doublet-chemotherapy + Cemiplimab vs Cemiplimab Monotherapy in Treatment Naive Older and Frail Patients With Metastatic NSCLC With PD-L1 <50% is a Phase 2 clinical trial sponsored by Swiss Cancer Institute studying Metastatic NSCLC - Non-Small Cell Lung Cancer. This trial compares a new, lower-dose chemotherapy combined with an immunotherapy drug against immunotherapy alone. It is for older or frail individuals with advanced lung cancer that has spread and has a specific marker (PD-L1 <50%). Participants will receive either the combination treatment or immunotherapy alone, and will be monitored for side effects and effectiveness. Standard treatment for this condition often involves full-dose chemotherapy, which can be difficult for older or frail patients to tolerate. The trial aims to enroll 156 participants.

Official 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.

Who Can Participate

Here is what you need to know about eligibility for this trial. You can join if you are 70 years or older and have advanced lung cancer that has spread. You must have a specific test result for PD-L1 (less than 50%) and be generally well enough to receive treatment, even if frail. You cannot join if you have certain genetic changes in your cancer, have had prior treatment for advanced lung cancer, or have active autoimmune diseases. Your doctor will assess if you are eligible based on your overall health and specific cancer characteristics. This trial is studying Metastatic NSCLC - Non-Small Cell Lung Cancer, so participants generally need a confirmed diagnosis. The trial is currently accepting new participants.

What They're Measuring

The main goal is to see how long patients live without their cancer getting worse, meaning the treatment is working to control the disease. The specific primary outcome measures are: Progression-free survival (PFS) (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.). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 2, which tests whether the treatment actually works against the target condition. Phase 2 trials involve 100-300 patients and continue to monitor safety while evaluating effectiveness. This phase often tests different dosages to find the optimal amount. About 33% of Phase 2 drugs advance to Phase 3. If successful, the treatment will move to large-scale Phase 3 trials needed for FDA approval.

Why This Trial Matters

This trial aims to find a more tolerable yet effective treatment for older and frail patients with advanced lung cancer, addressing the challenge of chemotherapy side effects in this population. Phase 2 success would typically lead to larger Phase 3 trials needed for regulatory approval. This research targets Metastatic NSCLC - Non-Small Cell Lung Cancer, where improved treatment options are needed.

Investor Insight

This trial targets a growing patient population (older adults with lung cancer) and explores a potentially less toxic treatment regimen, which could be a significant advancement if successful. Phase 2 trials have approximately a 15-20% chance of eventually gaining FDA approval.

Is This Trial Right for Me?

Ask your doctor about the specific chemotherapy drugs used, the potential side effects, and how often you will need to visit the clinic. Participation involves receiving study treatment, attending regular appointments for check-ups and tests, and reporting any new symptoms or side effects. You will be randomly assigned to one of the treatment groups, meaning you won't choose which treatment you receive. This trial is currently recruiting participants. The trial is being conducted at 17 sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: RANDOMIZED
• Model: PARALLEL
• Masking: NONE
• Enrollment: 156 participants

Interventions

• DRUG: Cemiplimab — cemiplimab IV 350 mg, day 1
• DRUG: Carboplatin — carboplatin IV AUC 3 day 1
• DRUG: Pemetrexed & Gemcitabine — pemetrexed IV 300 mg/m2 day 1 gemcitabine IV 600 mg/m2 day 1, d8
• DRUG: Paclitaxel — paclitaxel IV 50 mg/m2 day 1, d8

Primary Outcomes

• Progression-free survival (PFS) (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

• 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.)

Full Eligibility Criteria

Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Trial Locations

• HFR Fribourg, Fribourg, Villars-sur-Glâne, Switzerland
• Kantonsspital Aarau, Aarau, Switzerland
• Kantonsspital Baden, Baden, Switzerland
• Universitätsspital Basel, Basel, Switzerland
• Inselspital, Bern, Switzerland
• Kantonsspital Baselland, Bruderholz, Switzerland
• Kantonsspital Graubuenden, Chur, Switzerland
• Spital Thurgau AG - Kantonsspital Frauenfeld, Frauenfeld, Switzerland
• Hôpitaux Universitaires de Genève, Geneva, Switzerland
• Kantonsspital Olten - Solothurner Spitäler, Olten, Switzerland
• ...and 7 more locations

Frequently Asked Questions

Related Conditions

• Non-Small Cell Lung Cancer (NSCLC)
• Metastatic Lung Cancer
• Lung Adenocarcinoma
• Squamous Cell Lung Cancer
• Chemotherapy
• Immunotherapy
• Oncology
• Geriatric Oncology
• Cancer Treatment
• Targeted Therapy

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