• Age ≥18 years on day of signing informed consent.

• Specific by tumor cohorts:

• a. For the HSNCC cohort, histologically confirmed diagnosis of advanced and/or metastatic HSNCC suitable for first line immunotherapy.

• i. HPV+ and HPV- patients are allowed.

• ii. Primary tumor locations of oropharynx, oral cavity, hypopharynx, or larynx. Participants may not have a primary tumor site of nasopharynx (any histology) or salivary gland tumors.

• iii. PD-L1 status ≥ 1% per local CPS score. Samples should be provided to central lab for post-hoc centralized testing.

• iv. At least 12 months between last dose of prior adjuvant therapy and date of relapse diagnosis (if given). For the purposes of this protocol, prior adjuvant therapy only applies to full dose systemic chemotherapy (such as pre-operative systemic induction chemotherapy), but does not include radiation + surgery, or radiation + low or partial dose platinum radiosensitization. There is no time limit (washout) between the end of any prior radiation/ chemoradiation and the start of study drug v. No prior anti-PD-(L)1 treatment for HNSCC.

• b. For the melanoma cohorts, histologically confirmed diagnosis of advanced and/or metastatic cutaneous melanoma for which no existing options are considered to provide clinical benefit.

• i. Best response of uPR, SD or PD to an anti-PD-(L)1-containing regimen.

• ii. Prior anti-PD-(L)1 therapy must have lasted ≥ 12 weeks.

• iii. Radiological progression was demonstrated during or after therapy with a PD-(L)1 immune CPI (only one prior line of PD-(L)1 therapy is permitted.

• iv. If patient received anti-PD-1 as prior adjuvant therapy, patient should have relapsed during therapy or within the subsequent 6 months after last dose. Note: Progression on ipilimumab is not required.

• v. Patients with BRAF V600-positive tumor(s) should have received prior treatment with a BRAF inhibitor (alone or in combination with a MEK inhibitor) in addition to treatment with an anti-PD-1 or to have declined targeted therapy. Note: Patients with BRAF V600-positive tumors with no clinically significant tumor-related symptoms nor evidence of rapidly progressive disease are not required to be treated with a BRAF inhibitor (alone or in combination with a MEK inhibitor) based on investigator's decision

• c. For the CRC cohort, a histologically confirmed diagnosis of advanced and/or metastatic CRC.

• i. Received or are not eligible for standard of care fluoropyrimidine(s), oxaliplatin, irinotecan, anti-VEGF and EGFR-targeted therapies.

• ii. Non-microsatellite instability high (non-MSI high).

• iii. Progression on previous systemic therapy.

• At least one tumor lesion amenable to IT injection and biopsy that has not been previously irradiated.

• Measurable disease based on RECIST 1.1., including ≥ 1 measurable lesion(s) to be injected

• Performance status of 0 or 1 on the ECOG Performance Scale

• Life expectancy of \>3 months.

• Willingness to provide biological samples required for the duration of the study, including a fresh tumor biopsy sample whilst on study.

• Adequate organ function assessed by laboratory values obtained ≤14 days prior to enrollment