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

Melanoma (Skin) Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03291002
• Other study ID #: CV-8102-008
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: September 25, 2017
• Est. completion date: February 2023

Study information

• Verified date: November 2021
• Source: CureVac AG
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 98
• Est. completion date: February 2023
• Est. primary completion date: October 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

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

Intervention

Biological:
• CV8102
CV8102 alone
• CV8102 + anti-PD-1 therapy
CV8102 in combination with standard of care anti-PD-1 therapy

Locations

Country	Name	City	State
Austria	Medical University of Graz	Graz
Austria	Universitätsklinik für Dermatologie der Paracelsus medizinischen Privatuniversität Salzburg	Salzburg
France	Hôpital Saint Louis	Paris
France	Institut Gustave Roussy	Paris
Germany	Charité Benjamin Franklin	Berlin
Germany	Medizinische Klinik III, Universitätsklinikum Bonn, Hämatologie, Immunonkologie und Rheumatologie	Bonn
Germany	Elbe-Klinikum-Buxtehude, Hautkrebszentrum	Buxtehude
Germany	Universitätsklinikum Erlangen,Hautklinik, Internistisches Zentrum (INZ)	Erlangen
Germany	Nationales Centrum für Tumorerkrankungen (NCT) Heidelberg	Heidelberg
Germany	Universitätsklinikum Schleswig-Holstein, Klinik für Dermatologie, Allergologie und Venerologie	Lübeck
Germany	Fachklinik Hornheide	Münster
Germany	Universitätsklinikum Münster, Klinik für Hautkrankheiten, ZiD- Zentrum für innovative Dermatologie	Münster
Germany	Universitäts-Hautklinik, Abtl. Dermatologische Onkologie	Tübingen
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	Moscow
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.	Saint Petersburg
Spain	Hospital Duran i Reynals - Institut Catala dOncologia ICO	Barcelona
Spain	Hospital Universitari Vall d'Hebron	Barcelona
Spain	Hospital Ramon y Cajal	Madrid
Spain	Hospital Universitario Virgen de la Victoria	Málaga
Spain	Hospital Universitario Marqus de Valdecilla Santander	Santander

Sponsors (3)

Lead Sponsor	Collaborator
CureVac AG	Cromos Pharma LLC, Syneos Health

Countries where clinical trial is conducted

Austria,  France,  Germany,  Russian Federation,  Spain, 

Outcome

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