Safety and Tolerability of CVHNLC Plus Pembrolizumab in Patients With Squamous Non Small-Cell Lung Cancer (sqNSCLC)

NCT07073183 | Not Yet Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: CV-HNLC-0012024-519651-28-00
• Study Type: interventional
• Target: 36
• Locations: 3 countries
• Sites: 13

Brief Summary

This is an open-label, first-in-human, dose escalation study of CV09070101 mRNA (CVHNLC) in patients with metastatic Squamous Non-Small-Cell Lung Cancer (sqNSCLC). The study will evaluate the safety and tolerability of CVHNLC plus pembrolizumab in an Dose Escalation Part and, once the safety of this combination is established, CVHNLC plus prembrolizumab and chemotherapy (carboplatin and paclitaxel) will be evaluated in an Dose Expansion Part with the recommended dose selected from the Dose Escalation Part.

Conditions

Squamous NSCLC

Outcome Measures

Primary Outcomes (9)

• Incidence of treatment-related adverse events (TRAEs)

  1 year

• Incidence of treatment-emergent adverse events (TEAEs)

  1 year

• Incidence of serious adverse events (SAEs)

  1 year

• Incidence of adverse events of special interest (AESIs)

  1 year

• Incidence of immune-related adverse events (irAEs)

  1 year

• Incidence of injection site reactions (ISRs)

  1 year

• Incidence of medical attended adverse events (MAEs) treatment-emergent adverse events leading to treatment discontinuation

  1 year

• Incidence of clinically significant laboratory abnormalities per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v.5.0.

  1 year

• Number of patients with dose-limiting toxicities (DLTs) evaluated during the first 4 weeks of treatment (Dose Escalation Part only)

  1 year

Secondary Outcomes (4)

• Objective response rate based on best overall response assessed by the Investigator using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1). Response is defined as patients achieving either a complete response (CR) or partial respo

  1 year

• Progression-free survival (PFS) based on RECIST 1.1. Response is defined as time from first trial treatment to time of disease progression or death due to disease progression

  1 year

• Duration of response per RECIST 1.1, measured from the time of first documentation of response until first documentation of disease progression.

  1 year

• Disease control rate (DCR) at 3, 6, 9 and 12 months based on RECIST 1.1. Disease control is defined as stable disease (SD), partial response (PR) or complete response (CR).

  1 year

Study Arms (5)

Dose escalation: CVHNLC Dose level -1

EXPERIMENTAL

Dose level -1 represents a dose that may be evaluated if dose level 1 is poorly tolerated. No dose de-escalation below this level is planned for this study

Biological: CV09070101 mRNA vaccine (CVHNLC) 50 µg

Dose escalation: CVHNLC Dose level 1

EXPERIMENTAL

Biological: CV09070101 mRNA vaccine (CVHNLC) 100 µg

Dose escalation: CVHNLC Dose level 2

EXPERIMENTAL

Biological: CV09070101 mRNA vaccine (CVHNLC) 200 µg

Dose escalation: CVHNLC Dose level 3

EXPERIMENTAL

Biological: CV09070101 mRNA vaccine (CVHNLC) 400 µg

Dose expansion

EXPERIMENTAL

After completion of the dose-escalation part and safety data review by the DSMB, approximately 20 patients will be enrolled at the selected Recommended Dose for Expansion (RDE) to generate more data on safety, tolerability and immunogenicity.

Biological: CV09070101 mRNA vaccine (CVHNLC) 400 µg

Interventions

CV09070101 mRNA vaccine (CVHNLC) 50 µg BIOLOGICAL

CVHNLC will be administered as in IM injection (4x in induction treatment period, than during main treatment period every 3 weeks) plus pembrolizumab (3-weekly)

Dose escalation: CVHNLC Dose level -1

CV09070101 mRNA vaccine (CVHNLC) 100 µg BIOLOGICAL

CVHNLC will be administered as in IM injection (4x in induction treatment period, than during main treatment period every 3 weeks) plus pembrolizumab (3-weekly)

Dose escalation: CVHNLC Dose level 1

CV09070101 mRNA vaccine (CVHNLC) 200 µg BIOLOGICAL

CVHNLC will be administered as in IM injection (4x in induction treatment period, than during main treatment period every 3 weeks) plus pembrolizumab (3-weekly)

Dose escalation: CVHNLC Dose level 2

CV09070101 mRNA vaccine (CVHNLC) 400 µg BIOLOGICAL

CVHNLC will be administered as in IM injection (4x in induction treatment period, than during main treatment period every 3 weeks) plus pembrolizumab (3-weekly)

Dose escalation: CVHNLC Dose level 3

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Dose Escalation Part (Metastatic 1L Maintenance sqNSCLC)
• Patients with histologically confirmed metastatic Stage IV (per American Joint Commission on Cancer (AJCC) Staging Manual, Eighth Edition) sqNSCLC not amenable for surgical or locoregional therapy.
• Patients who have received pembrolizumab for 3 months but no longer than 6 months from start of pembrolizumab treatment (at least 3 cycles with a total dose of 600 mg), either as monotherapy or in combination with at least 2 cycles of chemotherapy with carboplatin and (nab-)paclitaxel as first-line treatment with no documented disease progression and who are indicated for maintenance therapy with pembrolizumab.
• Patients able to tolerate further anti-PD-1 therapy i.e., no criteria for permanent discontinuation of pembrolizumab due to toxicity have been met during previous treatment.
• No known targetable molecular aberration.
• Patients having measurable disease according to RECIST 1.1.
• Dose Expansion Part (Metastatic 1L sqNSCLC)
• \. Patients with histologically confirmed metastatic sqNSCLC (AJCC Staging Manual, Eighth Edition) not amenable for surgical or locoregional therapy and being eligible for first-line treatment with pembrolizumab and chemotherapy with carboplatin and paclitaxel. Patients should not have received any prior systemic treatment for metastatic disease. Previous (neo-)adjuvant treatment is allowed if there are at least 12 months between end of this treatment and development of metastatic disease.
• Available formalin-fixed paraffin-embedded (FFPE) tumor tissue samples from non- irradiated lesions that are not older than 6 months for retrospective assessment of antigen expression and potential other biomarker analyses (in total 15 slides of at least 5 μm thickness or equivalent amount provided as a single block).
• Recovered from all AEs related to prior therapies including anti-PD-(L)1 inhibitor treatment-related AEs to CTCAE Grade ≤ 1 or baseline (except for alopecia areata, vitiligo, chemotherapy induced polyneuropathy or endocrinopathies that are compensated by hormone replacement and Grade 2 lymphopenia).
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Age ≥ 18 years on date of signing informed consent form (ICF).
• Each patient must voluntarily sign and date an ICF approved by an Independent Ethics Committee (IEC), prior to the initiation of any, screening or trial-specific procedures.
• Life expectancy ≥ 6 months.
• Females who are post-menopausal (no menses for at least 12 months before the Screening Visit), or surgically sterile (bilateral tubal ligation, bilateral oophorectomy, or hysterectomy).

You may not qualify if:

• Disease progression on or within 12 months after the last dose of (neo-)adjuvant anti PD-(L)1 treatment before start of first-line treatment.
• Prior radiotherapy within 2 weeks before start of trial treatment.
• History of other malignancies unless the patient has undergone potentially curative treatment without evidence of recurrence within the last 3 years. Exception is BCC or carcinoma in situ of any site that has been adequately treated (with the exception of systemic therapy).
• Previous anaphylactic or severe allergic reaction to LNP-formulated drug or (mRNA) vaccine (or known allergy to any other component of CVHNLC).
• Allergy to aminoglycoside or beta-lactam antibiotics.
• History of previous permanent discontinuation of anti-PD-(L)1 therapy due to toxicity or any other contraindications to treatment with pembrolizumab, including severe hypersensitivity to anti-PD-1 checkpoint inhibitors, its active substance, or one of its excipients.
• Abnormal (≥ Grade 2 NCI-CTCAE v5.0) laboratory values as follows:
• Hemoglobin \< 10 g/dL (6.2 mmol/L).
• White blood cell (WBC) count decrease \< 2.5 ×109/L.
• Absolute neutrophil count (ANC) decrease \< 1.5 ×109/L.
• Absolute lymphocyte count (ALC) decrease \< 0.5 ×109/L.
• Platelet count decrease \< 75 ×109/L.
• Bilirubin \> 1.5 × upper limit of normal (ULN according to the performing lab's reference range), except for patients with Gilbert's syndrome.
• Alanine aminotransferase (ALT) \> 3 × ULN (or ≤ 5 in patients with liver metastasis).
• Aspartate aminotransferase (AST) \> 3 × ULN. (or ≤ 5 in patients with liver metastasis).

Sponsors & Collaborators

• CureVac: lead

Study Sites (13)

Virginia Cancer Center

Fairfax, Virginia, 22031, United States

Location

Virginia Commonwealth University, Massey Comprehensive Cancer Center, McGlothlin Medical Education Center

Richmond, Virginia, 23298, United States

Location

AP-HM - Hôpital Nord

Marseille, France

Location

Institut Curie - Hôpital de Paris

Paris, France

Location

CHU de Rennes - Hôpital Pontchaillou

Rennes, France

Location

Institut de Cancerologie de l'Ouest - Hôpital Saint Herblain - PPDS

Saint-Herblain, France

Location

Institut Claudius Regaud - PPDS

Toulouse, France

Location

Gustave Roussy

Villejuif, France

Location

Hospital Quironsalud Barcelona -NEXT Oncology

Barcelona, Spain, Spain

Location

Hospital Universitari Vall d´Hebron -Instituto de Investigacion Oncologica Vall dHebron (VHIO)

Barcelona, Spain, Spain

Location

Hospital Universitario Fundacion Jimenez Diaz - START MADRID

Madrid, Spain, Spain

Location

Hospital Universitario HM Sanchinarro - CIOCC - START MADRID

Madrid, Spain, Spain

Location

Hospital Regional Universitario Virgen de la Victoria

Málaga, Spain, Spain

Location

Study Officials

• Clinical Trial Information

  CureVac SE

  STUDY DIRECTOR

Central Study Contacts

Clinical Trial Information, CureVac SE

CONTACT

Please email; clinicaltrials@curevac.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Phase I

Study Record Dates

• First Submitted: July 9, 2025
• First Posted: July 18, 2025
• Study Start: July 30, 2025
• Primary Completion (Estimated): December 31, 2029
• Study Completion (Estimated): December 31, 2029
• Last Updated: July 18, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

ES (5); FR (6); US (2)