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

Phase I Study of Intratumoral CV8102 in Patients With Advanced Melanoma, Squamous Cell Carcinoma of the Skin, Squamous Cell Carcinoma of the Head and Neck, or Adenoid Cystic Carcinoma

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Carcinoma, Adenoid Cystic; Melanoma (Skin); Squamous Cell Carcinoma of the Skin; Carcinoma, Squamous Cell of Head and Neck
• Intervention / Treatment: Biological: CV8102; Biological: CV8102 + anti-PD-1 therapy

• Study Type: Interventional
• Enrollment (Actual): 98
• Phase: Phase 1

Contacts and Locations

Study Locations

• Austria
  • Graz, Austria
    • Medical University of Graz
  • Salzburg, Austria
    • Universitatsklinik fur Dermatologie der Paracelsus medizinischen Privatuniversitat Salzburg
• France
  • Paris, France
    • Hopital Saint Louis
  • Paris, France
    • Institut Gustave Roussy
• Germany
  • Berlin, Germany
    • Charité Benjamin Franklin
  • Bonn, Germany
    • Medizinische Klinik III, Universitätsklinikum Bonn, Hämatologie, Immunonkologie und Rheumatologie
  • Buxtehude, Germany
    • Elbe-Klinikum-Buxtehude, Hautkrebszentrum
  • Erlangen, Germany
    • Universitätsklinikum Erlangen,Hautklinik, Internistisches Zentrum (INZ)
  • Heidelberg, Germany
    • Nationales Centrum für Tumorerkrankungen (NCT) Heidelberg
  • Lübeck, Germany
    • Universitätsklinikum Schleswig-Holstein, Klinik für Dermatologie, Allergologie und Venerologie
  • Münster, Germany
    • Fachklinik Hornheide
  • Münster, Germany
    • Universitätsklinikum Münster, Klinik für Hautkrankheiten, ZiD- Zentrum für innovative Dermatologie
  • Tübingen, Germany
    • Universitäts-Hautklinik, Abtl. Dermatologische Onkologie
• Russian Federation
  • Moscow, Russian Federation
    • Center for Personalized Oncology, I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation
  • Moscow, Russian Federation
    • FSBI "National Medical Research Center of Oncology n.a. N.N. Blokhin" of the Ministry of Healthcare of the Russian Federation
  • Saint Petersburg, Russian Federation
    • FSBI "National Medical Research Oncology Center n.a. N.N. Petrov
  • Saint Petersburg, Russian Federation
    • Saint-Petersburg State University, Clinic of advanced medical technologies n. a. Nicolay I. Pirogov.
• Spain
  • Barcelona, Spain
    • Hospital Universitari Vall d'Hebrón
  • Barcelona, Spain
    • Hospital Duran i Reynals - Institut Catala dOncologia ICO
  • Madrid, Spain
    • Hospital Ramon y Cajal
  • Málaga, Spain
    • Hospital Universitario Virgen de la Victoria
  • Santander, Spain
    • Hospital Universitario Marqus de Valdecilla Santander

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Key Inclusion Criteria:

1. 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

2. 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

3. 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)

4. Patients enrolled into Cohort D2 (CV8102 in combination with anti-PD-1 therapy) must have

   • histologically confirmed advanced hnSCC
   • indication for treatment with first-line pembrolizumab (patients naive to anti-PD-1/anti-PD-L1)
   • PD-L1 combined positive score ≥ 1% according to local practice
5. Presence of at least one injectable tumor lesion that is measurable according to RECIST 1.1
6. Recovered from prior toxicities to CTCAE grade ≤ 1 or grade ≤ 2
7. Resolution of CPI-related adverse effects, if applicable (including irAEs) back to CTCAE grade 0/1
8. ECOG PS 0 or 1
9. 18 years of age or older
10. Adequate hematologic, renal, hepatic and coagulation function
11. Use of effective contraception

Key Exclusion Criteria:

1. Rapidly progressing multi-focal metastatic or acutely life threatening disease
2. Prior use of topical/localTLR-7/8 agonists within the past 6 months
3. Clinically active central nervous system metastases and/or carcinomatous meningitis (patients with stable brain metastases are eligible)
4. Ocular and mucosal melanoma
5. Prior anti-cancer therapy within specified time-periods depending on the indication
6. 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
7. 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)
8. 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
9. 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
10. Acute hypophysitis or endocrinopathies that are not adequately controlled by hormonal replacement therapy or thyreostatic treatment
11. Use of immune modulating drugs or immunologically active topical therapies within 28 days of administration of the first dose of study drug
12. 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
13. History of active autoimmune disease requiring immunosuppressive medication (except Vitiligo and except CPI-mediated irAEs)
14. Known hematologic malignancy or malignant primary solid tumor that have occured or reoccurred within the previous 5 years
15. Recent thromboembolic complications, or clinically significant cardiovascular disease, or any other uncontrolled illness that would pose a risk to patient safety
16. Severe infection or acute inflammatory state
17. Seropositivity for human immunodeficiency virus (HIV), hepatitis B virus (HBV) surface antigen (except in previously vaccinated patients) or hepatitis C virus (HCV)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort A; Dose escalation of CV8102	Biological: CV8102; CV8102 alone
Experimental: Cohort B; Optional expansion cohorts of CV8102	Biological: CV8102; CV8102 alone
Experimental: Cohort C; Dose escalation of CV8102 + anti-PD-1 therapy	Biological: CV8102 + anti-PD-1 therapy; CV8102 in combination with standard of care anti-PD-1 therapy
Experimental: Cohort D; Optional expansion of CV8102 + anti-PD-1 therapy	Biological: CV8102 + anti-PD-1 therapy; CV8102 in combination with standard of care anti-PD-1 therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tumor response	• Anti-tumor activity of CV8102 per irRECIST and RECIST 1.1	up to 12 months (end of study)
Disease status	• Tumor Assessment	6 months
Tumor response	• Extent of tumor response at injected and non-injected lesions, if applicable	up to 12 months (end of study)
Survival	• Survival time	up to 12 months (end of study)

Collaborators and Investigators

• Sponsor: CureVac
• Collaborators: Syneos Health; Cromos Pharma LLC
• Investigators: Principal Investigator: Thomas Eigentler, Prof. Dr., thomas.eigentler@charite.de

Publications and helpful links

General Publications

• 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. 2022 Nov 2. doi: 10.1007/s00262-022-03311-4. Online ahead of print.

Study record dates

Study Major Dates

• Study Start (Actual): September 25, 2017
• Primary Completion (Anticipated): October 1, 2022
• Study Completion (Anticipated): February 1, 2023

Study Registration Dates

• First Submitted: September 15, 2017
• First Submitted That Met QC Criteria: September 21, 2017
• First Posted (Actual): September 25, 2017

Study Record Updates

• Last Update Posted (Actual): November 4, 2021
• Last Update Submitted That Met QC Criteria: November 3, 2021
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Head and Neck Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Neoplasms, Squamous Cell; Carcinoma; Carcinoma, Adenoid Cystic; Melanoma; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; Skin Neoplasms
• Other Study ID Numbers: CV-8102-008

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

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