Study of mRNA-4359 Administered Alone and in Combination With Immune Checkpoint Blockade in Participants With Advanced Solid Tumors

Required: EGFR positive tumor mutation

Arm 2b: ... no known EGFR or ALK positive tumor mutations

Required: ALK positive tumor mutation

Arm 2b: ... no known EGFR or ALK positive tumor mutations

Required: PD-L1 (CD274) TPS ≥50% (TPS ≥50%)

Arm 2b: ... NSCLC with a PD-L1 TPS of ≥50%

Required: PD-L1 (CD274) TPS ≥1% (TPS ≥1%)

Arm 1b melanoma expansion cohort and Arm 2d: Central confirmation of PD-L1 TPS score is required prior to enrollment

Required: PD-L1 (CD274) TPS evaluable

Arm 2c: Sufficient tumor tissue (slides or FFPE block) for PD-L1 testing is required as per Laboratory Manual. ... may be replaced in this cohort if not PD-L1 evaluable.

Allowed: EGFR actionable mutation

For NSCLC participants with known EGFR, ALK, ... ROS1, or other actionable mutations for which there are approved targeted therapies, participants must have received prior approved targeted therapy or have been offered and declined approved targeted therapy.

Allowed: ALK actionable mutation

For NSCLC participants with known EGFR, ALK, ... ROS1, or other actionable mutations for which there are approved targeted therapies, participants must have received prior approved targeted therapy or have been offered and declined approved targeted therapy.

Allowed: ROS1 actionable mutation

For NSCLC participants with known EGFR, ALK, ... ROS1, or other actionable mutations for which there are approved targeted therapies, participants must have received prior approved targeted therapy or have been offered and declined approved targeted therapy.

Must have received: standard treatment regimen — advanced or metastatic

must have received, and then progressed, relapsed, or been intolerant to, or ineligible for, at least 1 standard treatment regimen in the advanced or metastatic setting

Must have received: immune checkpoint inhibitor — advanced or metastatic

CPI refractory melanoma or ... CPI refractory NSCLC ... must have primary refractory or acquired secondary resistance to prior immune checkpoint treatments

Cannot have received: concurrent anticancer therapy

Exception: local radiation for palliative care is permitted with approval from the Sponsor

concurrent anticancer therapy including other chemotherapy, radiation [local radiation for palliative care is permitted with approval from the Sponsor], hormonal anticancer treatment, biologic therapy, or immunotherapy

Cannot have received: investigational agent targeting both IDO1 and PD-L1

Prior exposure to any investigational or approved agent designed to simultaneously target both indoleamine 2,3-dioxygenase (IDO1) and PD-L1 is also exclusionary.