IO102-IO103 in Combination With Pembrolizumab Versus Pembrolizumab Alone in Advanced Melanoma (IOB-013 / KN-D18)

Inclusion Criteria:

1. Histologically or cytologically confirmed stage III (unresectable) or stage IVmelanoma, as per American Joint Committee on Cancer 8th edition guidelines notamenable to local therapy
2. Patients are treatment naive, that is, no previous systemic anticancer therapy forunresectable or metastatic melanoma. For clarification, the following patients areeligible:
3. Patients with BRAFV600 mutation-positive melanoma are eligible if treatment naiveand without rapidly progressive disease as per investigators assessment.Documented BRAF V600 mutation status must be available from all patients prior totrial entry.
4. Patients who have received previous adjuvant and/or neoadjuvant therapy withtargeted therapy or immune therapy are eligible if administered the last dose atleast 6 months before inclusion in this trial (randomization), and if relapse didnot occur during active treatment or within 6 months of treatmentdiscontinuation.
5. At least 1 measurable lesion according to response evaluation criteria for solidtumors (RECIST v1.1) and confirmed by IRC.
6. Provision of archival (obtained within 3 months), or newly acquired biopsy tissue notpreviously irradiated, and blood at screening for biomarker assessments.Formalin-fixed, paraffin embedded (FFPE) tissue blocks are preferred to slides. Newlyobtained biopsies are preferred to archived tissue.

Exclusion Criteria:

1. Patients with known or suspected central nervous system (CNS) metastases or with theCNS as the only site of active disease are excluded with the following exception: • Patients with controlled (stable) brain metastases will be allowed to enroll (subject to baseline magnetic resonance imaging (MRI) confirmation). Controlled (stable) brain metastases are defined as those with no radiographic progression for atleast 4 weeks after radiation and/or surgical treatment at the time of signed informedconsent. Patients must have been off steroids for at least 2 weeks before signedinformed consent and have no new or progressive neurological signs and symptoms.
2. Patient has received previous radiotherapy within 2 weeks of start of trial treatment (visit 2). Patients must have recovered from all radiation-related toxicities, notrequire corticosteroids, and not have had radiation pneumonitis. A 1-week washout ispermitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease.
3. Patients with BRAFV600-positive disease who are experiencing rapidly progressingdisease and/or have received standard first-line therapy with BRAF and/or MEKinhibitor for unresectable or metastatic disease. Other protocol defined inclusion/exclusion criteria may apply.