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

Sponsor

CureVac AG (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT03291002

Collaborator

Syneos Health (Other), Cromos Pharma LLC (Industry)

Enrollment

Locations

Arms

64.2

Anticipated Duration (Months)

4.5

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Melanoma (Skin) Squamous Cell Carcinoma of the Skin Carcinoma, Squamous Cell of Head and Neck Carcinoma, Adenoid Cystic	Biological: CV8102 Biological: CV8102 + anti-PD-1 therapy	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

98 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Intervention Model Description:

Open-label, cohort-based, dose escalation and expansion studyOpen-label, cohort-based, dose escalation and expansion study

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Sep 25, 2017

Anticipated Primary Completion Date :

Oct 1, 2022

Anticipated Study Completion Date :

Feb 1, 2023

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

Dose determination for dose escalation cohorts [2 weeks]
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
Incidence of treatment related (Serious) Adverse Events (Tolerability and Safety profile) [up to 12 months (end of study)]
• Tolerability and safety profile of CV8102 alone and in combination with anti-PD-1 antagonists

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Key Inclusion Criteria:

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
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

Presence of at least one injectable tumor lesion that is measurable according to RECIST 1.1
Recovered from prior toxicities to CTCAE grade ≤ 1 or grade ≤ 2
Resolution of CPI-related adverse effects, if applicable (including irAEs) back to CTCAE grade 0/1
ECOG PS 0 or 1
18 years of age or older
Adequate hematologic, renal, hepatic and coagulation function
Use of effective contraception

Key Exclusion Criteria:

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
Severe infection or acute inflammatory state
Seropositivity for human immunodeficiency virus (HIV), hepatitis B virus (HBV) surface antigen (except in previously vaccinated patients) or hepatitis C virus (HCV)

Contacts and Locations

Locations

	Site	City	Country
1	Medical University of Graz	Graz	Austria
2	Universitätsklinik für Dermatologie der Paracelsus medizinischen Privatuniversität Salzburg	Salzburg	Austria
3	Hôpital Saint Louis	Paris	France
4	Institut Gustave Roussy	Paris	France
5	Charité Benjamin Franklin	Berlin	Germany
6	Medizinische Klinik III, Universitätsklinikum Bonn, Hämatologie, Immunonkologie und Rheumatologie	Bonn	Germany
7	Elbe-Klinikum-Buxtehude, Hautkrebszentrum	Buxtehude	Germany
8	Universitätsklinikum Erlangen,Hautklinik, Internistisches Zentrum (INZ)	Erlangen	Germany
9	Nationales Centrum für Tumorerkrankungen (NCT) Heidelberg	Heidelberg	Germany
10	Universitätsklinikum Schleswig-Holstein, Klinik für Dermatologie, Allergologie und Venerologie	Lübeck	Germany
11	Fachklinik Hornheide	Münster	Germany
12	Universitätsklinikum Münster, Klinik für Hautkrankheiten, ZiD- Zentrum für innovative Dermatologie	Münster	Germany
13	Universitäts-Hautklinik, Abtl. Dermatologische Onkologie	Tübingen	Germany
14	Center for Personalized Oncology, I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation	Moscow	Russian Federation
15	FSBI "National Medical Research Center of Oncology n.a. N.N. Blokhin" of the Ministry of Healthcare of the Russian Federation	Moscow	Russian Federation
16	FSBI "National Medical Research Oncology Center n.a. N.N. Petrov	Saint Petersburg	Russian Federation
17	Saint-Petersburg State University, Clinic of advanced medical technologies n. a. Nicolay I. Pirogov.	Saint Petersburg	Russian Federation
18	Hospital Duran i Reynals - Institut Catala dOncologia ICO	Barcelona	Spain
19	Hospital Universitari Vall d'Hebron	Barcelona	Spain
20	Hospital Ramon y Cajal	Madrid	Spain
21	Hospital Universitario Virgen de la Victoria	Málaga	Spain
22	Hospital Universitario Marqus de Valdecilla Santander	Santander	Spain