Strategic reasons

A Phase 2 study investigating the efficacy and safety of ONCOS-102 alone or in combination with balstilimab (a programmed death receptor-1 [PD-1] inhibitor).

This study will test ONCOS-102 in combination with novel immune-targeted anti-cancer agents in patients with unresectable or metastatic cutaneous melanoma resistant to anti-PD (L)1 treatment. The purpose of this study is to further evaluate safety and tolerability, as well as anti-tumour activity of ONCOS-102 (both as monotherapy and in combination with anti-PD-1 balstilimab) in the target population.

Following a safety run-in period, up to approximately 63 participants with cutaneous melanoma who previously progressed on anti-PD-1/L1-based therapy will be allocated 1:1 to receive either ONCOS-102 alone or ONCOS-102 plus balstilimab.

Part 1 - Dose Exploration Run-in: Part 1 of the study will evaluate and further optimise the dose of ONCOS-102; a recommended phase 2 dose (RP2D) for ONCOS-102 will be identified.

Part 2 - Multiple Expansion: In the expansion phase, ONCOS-102 alone or in combination with balstilimab will be further evaluated in Cohorts 1 and 2 using the RP2D identified in Part 1.

The study is structured to allow for additional combination cohorts to be added to the study following a protocol amendment.

Inclusion Criteria:

1. Be willing and able to provide written informed consent for the study.

2. Be ≥ 18 years of age on the day of signing the informed consent form (ICF).

3. Eastern Co-operative Oncology Group (ECOG) performance status 0 or 1.

4. Histologically confirmed diagnosis of metastatic or unresectable malignant melanoma at screening with measurable disease (by RECIST v1.1) that is accessible for IT injection into cutaneous or subcutaneous lesions.

5. Resistant to PD-(L)1 blockade (primary or secondary resistance in the advanced setting or relapse after adjuvant therapy) either as monotherapy or in combination with other therapies, as defined by the following criteria:

   • Received at least 1 prior anti-PD-[L]1 immunotherapy regimen for a minimum of 6 weeks.
   • Prior progression must be either on treatment with anti-PD-(L)1 or ≤ 12 weeks from last dose in metastatic setting or relapse ≤ 24 weeks from completion of therapy in adjuvant setting.
   • Has demonstrated disease progression (PD) after anti-PD-(L)1 as defined by RECIST v1.1. The initial evidence of PD is to be confirmed by a second assessment (i.e., a confirmatory scan no less than 4 weeks from the date of the first documented PD), in the absence of clear clinical progression.

6. Has recovered from all adverse events (AEs) due to previous therapies to ≤ Grade 1 or baseline. Patients with ≤ Grade 2 endocrinopathies stable on mediation, stable neuropathy, and alopecia are eligible.

Exclusion Criteria:

1. Uveal or mucosal melanoma.

2. Any history of National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Grade ≥ 3 immune-mediated toxicity (excluding endocrinopathies and non-necrotising/bullous rash) from prior checkpoint inhibition.

   • If prior severe toxicity occurred during combination treatment with anti-PD-(L)1 + anti-cytotoxic lymphocyte associated antigen 4 (CTLA-4) but subsequent treatment with anti-PD-(L)1 as monotherapy was tolerated, the patient may be eligible for inclusion after discussion with the medical monitor.

3. Has known (current or previously treated) central nervous system metastases and/or carcinomatous meningitis.