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

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ClinicalTrials.gov Identifier: NCT03291002
Recruitment Status : Recruiting
First Posted : September 25, 2017
Last Update Posted : January 22, 2021
Sponsor:
Collaborator:
Syneos Health
Information provided by (Responsible Party):
CureVac AG

Tracking Information
First Submitted Date  ICMJE September 15, 2017
First Posted Date  ICMJE September 25, 2017
Last Update Posted Date January 22, 2021
Actual Study Start Date  ICMJE September 25, 2017
Estimated Primary Completion Date October 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 18, 2021)
  • Dose determination for dose escalation cohorts [ Time Frame: 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) [ Time Frame: up to 12 months (end of study) ]
    • Tolerability and safety profile of CV8102 alone and in combination with anti-PD-1 antagonists
Original Primary Outcome Measures  ICMJE
 (submitted: September 21, 2017)
  • Dose determination for dose escalation cohorts [ Time Frame: 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 anti-PD-1 therapy
  • Incidence of treatment related (Serious) Adverse Events (Tolerability and Safety profile) [ Time Frame: up to 9 months (end of study) ]
    • Tolerability and safety profile of CV8102 alone and in combination with anti-PD-1 therapy
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 18, 2021)
  • Tumor response [ Time Frame: up to 12 months (end of study) ]
    • Anti-tumor activity of CV8102 per irRECIST and RECIST 1.1
  • Disease status [ Time Frame: 6 months ]
    • Tumor Assessment
  • Tumor response [ Time Frame: up to 12 months (end of study) ]
    • Extent of tumor response at injected and non-injected lesions, if applicable
  • Survival [ Time Frame: up to 12 months (end of study) ]
    • Survival time
Original Secondary Outcome Measures  ICMJE
 (submitted: September 21, 2017)
  • Tumor response [ Time Frame: up to 9 months (end of study) ]
    • Anti-tumor activity of CV8102 per irRECIST and RECIST 1.1
  • Disease status [ Time Frame: 6 months ]
    • Tumor Assessment
  • Tumor response [ Time Frame: up to 9 months (end of study) ]
    • Extent of tumor response at injected and non-injected lesions, if applicable
  • Survival [ Time Frame: up to 9 months (end of study) ]
    • Survival time
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of Intratumoral CV8102 in cMEL, cSCC, hnSCC, and ACC
Official Title  ICMJE 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
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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Intervention Model Description:
Open-label, cohort-based, dose escalation and expansion study
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Melanoma (Skin)
  • Squamous Cell Carcinoma of the Skin
  • Carcinoma, Squamous Cell of Head and Neck
  • Carcinoma, Adenoid Cystic
Intervention  ICMJE
  • Biological: CV8102
    CV8102 alone
  • Biological: CV8102 + anti-PD-1 therapy
    CV8102 in combination with standard of care anti-PD-1 therapy
Study Arms  ICMJE
  • Experimental: Cohort A
    Dose escalation of CV8102
    Intervention: Biological: CV8102
  • Experimental: Cohort B
    Optional expansion cohorts of CV8102
    Intervention: Biological: CV8102
  • Experimental: Cohort C
    Dose escalation of CV8102 + anti-PD-1 therapy
    Intervention: Biological: CV8102 + anti-PD-1 therapy
  • Experimental: Cohort D
    Optional expansion of CV8102 + anti-PD-1 therapy
    Intervention: Biological: CV8102 + anti-PD-1 therapy
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: January 18, 2021)
98
Original Estimated Enrollment  ICMJE
 (submitted: September 21, 2017)
104
Estimated Study Completion Date  ICMJE February 2023
Estimated Primary Completion Date October 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Thomas Eigentler, Prof. Dr. +49 7071 298 4553 thomas.eigentler@med.uni-tuebingen.de
Listed Location Countries  ICMJE Austria,   France,   Germany,   Spain
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03291002
Other Study ID Numbers  ICMJE CV-8102-008
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party CureVac AG
Study Sponsor  ICMJE CureVac AG
Collaborators  ICMJE Syneos Health
Investigators  ICMJE
Principal Investigator: Thomas Eigentler, Prof. Dr. thomas.eigentler@med.uni-tuebingen.de
PRS Account CureVac AG
Verification Date January 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP