Clinical trial NCT03291002: Study of Intratumoral CV8102 in cMEL, cSCC, hnSCC, and ACC
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Melanoma (Skin)
Squamous Cell Carcinoma of the Skin
Carcinoma, Squamous Cell of Head and Neck
Carcinoma, Adenoid Cystic
Lead sponsor: CureVac
Sponsor class: INDUSTRY
Collaborators: name: Syneos Health
name: Cromos Pharma LLC
First posted: 2017-09-25
Enrollment: 98
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Intervention model description: Open-label, cohort-based, dose escalation and expansion study
Primary purpose: TREATMENT

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.


Eligibility criteria: 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)

Primary outcomes:
measure: Dose determination for dose escalation cohorts
timeFrame: 2 weeks
measure: Incidence of treatment related (Serious) Adverse Events (Tolerability and Safety profile)
timeFrame: up to 12 months (end of study)
Secondary outcomes:
measure: Tumor response
timeFrame: up to 12 months (end of study)
measure: Disease status
timeFrame: 6 months
measure: Tumor response
timeFrame: up to 12 months (end of study)
measure: Survival
timeFrame: up to 12 months (end of study)
Other outcomes:
Locations:
city: Graz
country: Austria
facility: Medical University of Graz
city: Salzburg
country: Austria
facility: Universitätsklinik für Dermatologie der Paracelsus medizinischen Privatuniversität Salzburg
city: Paris
country: France
facility: Hôpital Saint Louis
city: Paris
country: France
facility: Institut Gustave Roussy
city: Berlin
country: Germany
facility: Charité Benjamin Franklin
city: Bonn
country: Germany
facility: Medizinische Klinik III, Universitätsklinikum Bonn, Hämatologie, Immunonkologie und Rheumatologie
city: Buxtehude
country: Germany
facility: Elbe-Klinikum-Buxtehude, Hautkrebszentrum
city: Erlangen
country: Germany
facility: Universitätsklinikum Erlangen,Hautklinik, Internistisches Zentrum (INZ)
city: Heidelberg
country: Germany
facility: Nationales Centrum für Tumorerkrankungen (NCT) Heidelberg
city: Lübeck
country: Germany
facility: Universitätsklinikum Schleswig-Holstein, Klinik für Dermatologie, Allergologie und Venerologie
city: Münster
country: Germany
facility: Fachklinik Hornheide
city: Münster
country: Germany
facility: Universitätsklinikum Münster, Klinik für Hautkrankheiten, ZiD- Zentrum für innovative Dermatologie
city: Tübingen
country: Germany
facility: Universitäts-Hautklinik, Abtl. Dermatologische Onkologie
city: Moscow
country: Russian Federation
facility: Center for Personalized Oncology, I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation
city: Moscow
country: Russian Federation
facility: FSBI "National Medical Research Center of Oncology n.a. N.N. Blokhin" of the Ministry of Healthcare of the Russian Federation
city: Saint Petersburg
country: Russian Federation
facility: FSBI "National Medical Research Oncology Center n.a. N.N. Petrov
city: Saint Petersburg
country: Russian Federation
facility: Saint-Petersburg State University, Clinic of advanced medical technologies n. a. Nicolay I. Pirogov.
city: Barcelona
country: Spain
facility: Hospital Duran i Reynals - Institut Catala dOncologia ICO
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Madrid
country: Spain
facility: Hospital Ramon y Cajal
city: Málaga
country: Spain
facility: Hospital Universitario Virgen de la Victoria
city: Santander
country: Spain
facility: Hospital Universitario Marqus de Valdecilla Santander
Study officials:
affiliation: thomas.eigentler@charite.de
name: Thomas Eigentler, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.