Study of Intratumoral CV8102 in cMEL, cSCC, hnSCC, and ACC

NCT03291002 | Unknown Phase 1 DMC

• 1 other identifier: CV-8102-008
• Study Type: interventional
• Target: 98
• Locations: 5 countries
• Sites: 22

Brief Summary

This study evaluates intratumoral administration of CV8102 in patients with advanced melanoma, squamous cell carcinoma of the skin, squamous cell carcinoma of the head and neck, or adenoid cystic carcinoma. Patients will receive CV8102 as single agent or in combination with SoC anti-PD-1 therapy.

Conditions

Melanoma (Skin); Squamous Cell Carcinoma of the Skin; Carcinoma, Squamous Cell of Head and Neck; Carcinoma, Adenoid Cystic

Outcome Measures

Primary Outcomes (2)

• Dose determination for dose escalation cohorts

  * Maximum tolerated dose (MTD) and recommended dose (RD), respectively, for CV8102 alone * MTD and recommended combination dose (RCD) for CV8102 in combination with the standard dose of an anti-PD-1 antagonist

  2 weeks

• Incidence of treatment related (Serious) Adverse Events (Tolerability and Safety profile)

  • Tolerability and safety profile of CV8102 alone and in combination with anti-PD-1 antagonists

  up to 12 months (end of study)

Secondary Outcomes (4)

• Tumor response

  up to 12 months (end of study)

• Disease status

  6 months

• Tumor response

  up to 12 months (end of study)

• Survival

  up to 12 months (end of study)

Study Arms (4)

Cohort A

EXPERIMENTAL

Dose escalation of CV8102

Biological: CV8102

Cohort B

EXPERIMENTAL

Optional expansion cohorts of CV8102

Biological: CV8102

Cohort C

EXPERIMENTAL

Dose escalation of CV8102 + anti-PD-1 therapy

Biological: CV8102 + anti-PD-1 therapy

Cohort D

EXPERIMENTAL

Optional expansion of CV8102 + anti-PD-1 therapy

Biological: CV8102 + anti-PD-1 therapy

Interventions

CV8102 BIOLOGICAL

CV8102 alone

Cohort A; Cohort B

CV8102 + anti-PD-1 therapy BIOLOGICAL

CV8102 in combination with standard of care anti-PD-1 therapy

Cohort C; Cohort D

Eligibility Criteria

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

You may qualify if:

• Patients enrolled into Cohorts A and B (single agent CV8102) must have:
• histologically confirmed advanced cutaneous melanoma, cutaneous squamous cell carcinoma, head and neck squamous cell carcinoma, or adenoid cystic carcinoma with documented disease progression
• not amenable to surgical resection or locoregional radiation therapy with curative intent
• at least 1 line of anti-cancer therapy for advanced disease (except adenoid cystic carcinoma) and documented Progression
• cutaneous melanoma Cohort B3: Willing to undergo baseline and post-baseline biopsy of the lesion which is to be injected
• Patients enrolled into Cohort C (CV8102 in combination with anti-PD-1 therapy) must have
• histologically confirmed advanced cMEL or hnSCC
• indication for anti-PD-1 therapy or currently receiving anti-PD-1 therapy with stable of slowly progressing disease after at last 8 weeks (hnSCC) or 12 weeks (cMEL) of anti-PD-1 therapy prior to Day 1
• Patients enrolled into Cohort D1 (CV8102 in combination with anti-PD-1 therapy) must have
• histologically confirmed advanced cMEL
• either anti-PD-1 naive patients with indication for anti-PD-1 therapy (Cohort D1a) or patients refractory to anti-PD-1 therapy (Cohort D1b)
• Presence of measurable lesion(s) according to RECIST 1.1, not intended for injection
• Willing to undergo tumor biopsies at specific timepoints (Cohort D1a: baseline; Cohort D1b baseline and post-baseline biopsy of the injected lesion - only for selected sites)
• Patients enrolled into Cohort D2 (CV8102 in combination with anti-PD-1 therapy) must have
• histologically confirmed advanced hnSCC

You may not qualify if:

• Rapidly progressing multi-focal metastatic or acutely life threatening disease
• Prior use of topical/localTLR-7/8 agonists within the past 6 months
• Clinically active central nervous system metastases and/or carcinomatous meningitis (patients with stable brain metastases are eligible)
• Ocular and mucosal melanoma
• Prior anti-cancer therapy within specified time-periods depending on the indication
• Tumor lesions that are to be injected close to major blood vessels or nerves, or whose injection could potentially result in clinical adverse effects if post-treatment tumor swelling or inflammation were to occur
• Lesions that are to be injected in previously irradiated areas unless progressive tumor growth has been demonstrated (no prior irradiation of injected lesions on patients with melanoma)
• History of active coagulation or bleeding disorder or need for ongoing therapeutic anticoagulation that cannot be safely interrupted at th etime of IT injection or biopsy du eto Underlying medical conditions; patients with melanoma and cutaneous squamous cell carcinoma with controlled oral anticoagulation are eligible
• Treatment with any investigational anticancer agent within 30 days or 5 half-lives (whichever is longer) prior to the first dose of study drug or planned during the study
• Acute hypophysitis or endocrinopathies that are not adequately controlled by hormonal replacement therapy or thyreostatic treatment
• Use of immune modulating drugs or immunologically active topical therapies within 28 days of administration of the first dose of study drug
• Chronic systemic immunosuppressive therapy including chronic corticosteroids within 28 days of the first dose of study drug (except physiological maintenance/replacement steroid doses, topical steroids outside the injected lesion or inhaled steroids); patients are eligible if steroid requirement is \< 10 mg/day of prednisone (or equivalent) for at least 2 weeks
• History of active autoimmune disease requiring immunosuppressive medication (except Vitiligo and except CPI-mediated irAEs)
• Known hematologic malignancy or malignant primary solid tumor that have occured or reoccurred within the previous 5 years
• Recent thromboembolic complications, or clinically significant cardiovascular disease, or any other uncontrolled illness that would pose a risk to patient safety

Sponsors & Collaborators

• CureVac: lead
• Syneos Health: collaborator
• Cromos Pharma LLC: collaborator

Study Sites (22)

Medical University of Graz

Graz, Austria

Location

Universitätsklinik für Dermatologie der Paracelsus medizinischen Privatuniversität Salzburg

Salzburg, Austria

Location

Hôpital Saint Louis

Paris, France

Location

Institut Gustave Roussy

Paris, France

Location

Charité Benjamin Franklin

Berlin, Germany

Location

Medizinische Klinik III, Universitätsklinikum Bonn, Hämatologie, Immunonkologie und Rheumatologie

Bonn, Germany

Location

Elbe-Klinikum-Buxtehude, Hautkrebszentrum

Buxtehude, Germany

Location

Universitätsklinikum Erlangen,Hautklinik, Internistisches Zentrum (INZ)

Erlangen, Germany

Location

Nationales Centrum für Tumorerkrankungen (NCT) Heidelberg

Heidelberg, Germany

Location

Universitätsklinikum Schleswig-Holstein, Klinik für Dermatologie, Allergologie und Venerologie

Lübeck, Germany

Location

Fachklinik Hornheide

Münster, Germany

Location

Universitätsklinikum Münster, Klinik für Hautkrankheiten, ZiD- Zentrum für innovative Dermatologie

Münster, Germany

Location

Universitäts-Hautklinik, Abtl. Dermatologische Onkologie

Tübingen, Germany

Location

Center for Personalized Oncology, I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation

Moscow, Russia

Location

FSBI "National Medical Research Center of Oncology n.a. N.N. Blokhin" of the Ministry of Healthcare of the Russian Federation

Moscow, Russia

Location

FSBI "National Medical Research Oncology Center n.a. N.N. Petrov

Saint Petersburg, Russia

Location

Saint-Petersburg State University, Clinic of advanced medical technologies n. a. Nicolay I. Pirogov.

Saint Petersburg, Russia

Location

Hospital Duran i Reynals - Institut Catala dOncologia ICO

Barcelona, Spain

Location

Hospital Universitari Vall d'Hebron

Barcelona, Spain

Location

Hospital Ramon y Cajal

Madrid, Spain

Location

Hospital Universitario Virgen de la Victoria

Málaga, Spain

Location

Hospital Universitario Marqus de Valdecilla Santander

Santander, Spain

Location

Related Publications (2)

• Eigentler T, Thomas I, Samoylenko I, Erdmann M, Heinzerling L, Ochsenreither S, Krauss J, Oberoi A, Robert C, Lebbe C, Martin-Liberal J, Koch L, Richtig E, Terheyden P, Weishaupt C, Mohr P, Semiletova Y, Perez CL, Brossart P, Bauernfeind FG, Fluck M, Poltoratskiy A, Sekacheva M, Soria A, Schmitt-Bormann B, Gonzalez M, Hess J, Wengenmayer P, Seibel T, Koch SD, Quintini G, Codo P, Falk M, Schonborn-Kellenberger O, Gnad-Vogt U. Phase I study of intratumoral administration of CV8102 in patients with advanced melanoma, squamous cell carcinoma of the skin, squamous cell carcinoma of the head and neck, or adenoid cystic carcinoma. J Immunother Cancer. 2025 Feb 4;13(2):e009352. doi: 10.1136/jitc-2024-009352.

  PMID: 39904560 DERIVED

• Lutz J, Meister M, Habbeddine M, Fiedler K, Kowalczyk A, Heidenreich R. Local immunotherapy with the RNA-based immune stimulator CV8102 induces substantial anti-tumor responses and enhances checkpoint inhibitor activity. Cancer Immunol Immunother. 2023 May;72(5):1075-1087. doi: 10.1007/s00262-022-03311-4. Epub 2022 Nov 2.

  PMID: 36319717 DERIVED

MeSH Terms

Conditions

Melanoma; Squamous Cell Carcinoma of Head and Neck; Carcinoma, Adenoid Cystic

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases; Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Head and Neck Neoplasms; Adenocarcinoma

Study Officials

• Thomas Eigentler, Prof. Dr.

  thomas.eigentler@charite.de

  PRINCIPAL INVESTIGATOR

Study Design

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

Model Details: Open-label, cohort-based, dose escalation and expansion study

Study Record Dates

• First Submitted: September 15, 2017
• First Posted: September 25, 2017
• Study Start: September 25, 2017
• Primary Completion: October 1, 2022
• Study Completion: February 1, 2023
• Last Updated: November 4, 2021

Record last verified: 2021-11

Data Sharing

• IPD Sharing: Will not share

Locations

AU (2); ES (5); DE (9); FR (2); RU (4)