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

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)