AACR 2026 – Moderna touts first-line data

22 April 2026

The IDO/PD-L1 project mRNA-4359 shows early hints in first-line melanoma.

Moderna’s IDO x PD-L1 immunotherapy mRNA-4359 has already shown promise, alongside Keytruda, in checkpoint inhibitor-refractory melanoma, and now the company is highlighting data for the doublet in first-line disease.The results from a phase 1/2 trial, presented at AACR on Monday, have been claimed to look better than those seen historically with Keytruda monotherapy, according to the presenter, Dr Pavlina Spiliopoulou of the University of Glasgow. However, she conceded that patients numbers in Moderna’s study were “extremely small”.She detailed an 83% best response rate among 12 patients receiving mRNA-4359 plus Keytruda; however, this result relies heavily on unconfirmed responses, and no detail was provided to spell out how many responses had actually been confirmed.Notwithstanding this caveat, Spiliopoulou noted an ORR of 30-40% with Keytruda monotherapy in first-line melanoma. For example, the Keynote-006 trial produced a 34% ORR.The overall number with mRNA-4359 was clearly driven by PD-L1-positive patients, but there were also responses among PD-L1-negatives. mRNA-4359 in first-line melanoma MRNA-4359 + KeytrudaStudyPh1/2 mRNA-4359-P101VenueAACR 2026Cutoff1 Dec 2025Best response rate83% (10/12)- best response rate in PD-L1≥1%88% (7/8)- best response rate in PD-L1<1%67% (2/3)Source: Dr Pavlina Spiliopoulou & AACR. This is in contrast to data from the same study in PD-(L)1 refractory melanoma, presented at ESMO, which found no responses among PD-L1 negatives, versus a 67% ORR among nine PD-L1 expressers.mRNA-4359 delivers mRNA encoding IDO and PD-L1 antigens. The idea is that, once manufactured and displayed by antigen-presenting cells, these antigens will activate T cells that can then eliminate tumour cells.Moderna had been competing with IO Biotech, whose rival IDO x PD-L1 immunotherapy Cylembio plus Keytruda narrowly failed to beat Keytruda alone in the pivotal first-line melanoma trial, Keynote-D18. IO had hoped to continue, but finally threw in the towel in January.Moderna also has plans for mRNA-4359 plus Keytruda in first-line NSCLC. No other IDO x PD-L1 projects are in the clinic, according to OncologyPipeline.

The results from a phase 1/2 trial, presented at AACR on Monday, have been claimed to look better than those seen historically with Keytruda monotherapy, according to the presenter, Dr Pavlina Spiliopoulou of the University of Glasgow. However, she conceded that patients numbers in Moderna’s study were “extremely small”.

She detailed an 83% best response rate among 12 patients receiving mRNA-4359 plus Keytruda; however, this result relies heavily on unconfirmed responses, and no detail was provided to spell out how many responses had actually been confirmed.

Notwithstanding this caveat, Spiliopoulou noted an ORR of 30-40% with Keytruda monotherapy in first-line melanoma. For example, the Keynote-006 trial produced a 34% ORR.

The overall number with mRNA-4359 was clearly driven by PD-L1-positive patients, but there were also responses among PD-L1-negatives.

mRNA-4359 in first-line melanoma

	MRNA-4359 + Keytruda
Study	Ph1/2 mRNA-4359-P101
Venue	AACR 2026
Cutoff	1 Dec 2025
Best response rate	83% (10/12)
- best response rate in PD-L1≥1%	88% (7/8)
- best response rate in PD-L1<1%	67% (2/3)

Source: Dr Pavlina Spiliopoulou & AACR.

This is in contrast to data from the same study in PD-(L)1 refractory melanoma, presented at ESMO, which found no responses among PD-L1 negatives, versus a 67% ORR among nine PD-L1 expressers.

mRNA-4359 delivers mRNA encoding IDO and PD-L1 antigens. The idea is that, once manufactured and displayed by antigen-presenting cells, these antigens will activate T cells that can then eliminate tumour cells.

Moderna had been competing with IO Biotech, whose rival IDO x PD-L1 immunotherapy Cylembio plus Keytruda narrowly failed to beat Keytruda alone in the pivotal first-line melanoma trial, Keynote-D18. IO had hoped to continue, but finally threw in the towel in January.

Moderna also has plans for mRNA-4359 plus Keytruda in first-line NSCLC. No other IDO x PD-L1 projects are in the clinic, according to OncologyPipeline.