A Randomized Phase II Trial of Cemiplimab Plus OSE2101 ( TEDOPI®) as Maintenance Therapy in ctDNA Positive NSCL. The Cemited Study. (Cemited)

This is a phase II randomized study investigating whether a combination maintenance with Cemiplimab and OSE2101 (TEDOPI®) could increase ctDNA clearance rate versus standard maintenance therapy in HLA-A2 positive NSCLC patients not progressing after 4 cycles of chemo-immunotherapy.

Study Overview

• Status: Recruiting
• Conditions: NSCLC
• Intervention / Treatment: Drug: Cemiplimab; Drug: Tedopi

Detailed Description

This is a phase II randomized study investigating whether a combination maintenance with Cemiplimab and OSE2101 (TEDOPI®) could increase ctDNA clearance rate versus standard maintenance therapy in HLA-A2 positive NSCLC patients not progressing after 4 cycles of chemo-immunotherapy.

NSCLC patients with any histology, irrespective of PD-L1 expression levels and candidates for first line metastatic therapy will be screened for HLA-A2 status.

After evaluation of all inclusion and exclusion criteria and after informed consent signature, all eligible patients will receive up to four cycles of chemotherapy and Cemiplimab. The chemotherapy regimen will be selected by the investigator, in accordance with current clinical practice, favoring the use of platinum-based chemotherapy agents.

Patients not progressing after 4 cycles of chemo-immunotherapy will be evaluated for the cTDNA presence (baseline).

If they are positive for ctDNA will be further randomized to standard maintenance therapy or to the combination maintenance of Cemiplimab and OSE2101 (TEDOPI®). In case of ctDNA negative test will be treated with Cemiplimab according to clinical practice.

ctDNA will be further evaluated before cycle 3, and at the time of disease progression or at the end of maintenance therapy.

To summarize ctDNA will be analyzed in patients not progressing after 4 cycles of chemo-immunotherapy (before randomization), during the maintenance therapy and at the time of progression.

An additional blood sample will be collected in all patients at the time of starting first-line chemo-immunotherapy (pre-baseline).

• Study Type: Interventional
• Enrollment (Estimated): 160
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Federico Cappuzzo, Medical Oncology; Phone Number: +390652665789; Email: federico.cappuzzo@fondazionefort.org

Study Locations

• Italy
  • RM
    • Roma, RM, Italy, 00144
      • Recruiting
      • Istituti Fisioterapici Ospitalieri- Ifo - Istituto Regina Elena
      • Contact: Federico Cappuzzo, MD; Phone Number: +39 06.5266.5698; Email: federico.cappuzzo@ifo.it
      • Contact: Lorenza Landi, MD; Phone Number: +39 3397728272; Email: lorenza.landi@ifo.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Histologically or cytologically confirmed diagnosis of non- oncogene addicted advanced, locally advanced (not suitable for definitive chemoradiation therapy) or metastatic non-small-cell lung cancer (NSCLC)
• Any patient candidate for first line chemo-immunotherapy irrespective of PD-L1 levels
• HLA-A2 positive
• ECOG PS 0-1
• Signed informed consent (IC) prior to any trial-specific procedures

Exclusion Criteria:

• Patients not candidate for chemo-immunotherapy
• HLA-A2 negative
• Symptomatic or not previously treated and not stable brain metastases. Brain metastases are allowed if asymptomatic or pretreated
• Tumor tissue not available (archive or collected before trial inclusion)
• Evidence of EGFR mutations or ALK or ROS1 rearrangements
• Performance status >1 (ECOG)
• Diagnosis of another cancer in the last 3 years, except for in situ carcinoma of cervix, breast and bladder or skin carcinoma(squamous or basaloid)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: A; Cemiplimab 350 mg iv q21 single agent (squamous histology) or Cemiplimab 350 mg iv q21 plus pemetrexed 500mg/m2 q21 (non- squamous histology).	Drug: Cemiplimab; Cemiplimab +/-Pemetrexed (ARM A: standard arm)
Experimental: B; Cemiplimab 350 mg iv q 21 plus OSE2101 (TEDOPI®). The OSE2101 (TEDOPI®) dose to be injected is of 1 mL (5 mg of drug product) by subcutaneousubcutaneous administration	Drug: Tedopi; Cemiplimab + OSE2101 (TEDOPI®) (ARM B: experimental arm); Other Names: Cemiplimab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ctDNA clearance rate	Differences in ctDNA clearance rate in the two arms of treatment Differences in ctDNA clearance rate in the two arms of treatment Differences in ctDNA clearance rate in the two arms of treatment Differences in ctDNA clearance rate in the two arms of treatment	48 months

Collaborators and Investigators

• Sponsor: Fondazione Ricerca Traslazionale

Study record dates

Study Major Dates

• Study Start (Actual): April 17, 2025
• Primary Completion (Estimated): October 1, 2027
• Study Completion (Estimated): October 1, 2029

Study Registration Dates

• First Submitted: November 24, 2025
• First Submitted That Met QC Criteria: November 24, 2025
• First Posted (Estimated): December 4, 2025

Study Record Updates

• Last Update Posted (Estimated): December 4, 2025
• Last Update Submitted That Met QC Criteria: November 24, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: cemiplimab
• Other Study ID Numbers: CEMITED

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No