Utilizing Machine Learning to Identify Multimodal Signatures for Patients Who Would Benefit from the Addition of Tremelimumab to Durvalumab and Chemotherapy (TRIDENT)

Original title: Utilizing Machine Learning to Identify Multimodal Signatures for Patients Who Would Benefit from the Addition of Tremelimumab to Durvalumab and Chemotherapy (TRIDENT).

By Skoulidis, Jabbour, Garon +19Clinical cancer research : an official journal of the American Association for Cancer ResearchOct 1, 2026

Score█████░░░░░4.8

Key numbers

50% of patients with nonsquamous
95% confidence interval

VerdictWorth a reader's time today.

Read the original

Abstract

Purpose POSEIDON (NCT03164616) was a randomized, open-label, multicenter phase III trial comparing first-line durvalumab with or without tremelimumab in combination with chemotherapy versus chemotherapy alone in patients with metastatic non-small cell lung cancer (NSCLC). Overall survival (OS) and progression-free survival were significantly increased in the tremelimumab plus durvalumab and chemotherapy arm. We conducted a post hoc analysis (TRIDENT) to identify patients who may receive greater OS benefit from the addition of tremelimumab to durvalumab and chemotherapy. Experimental design This analysis included clinical, genomic, and radiomic data from the POSEIDON trial (data cutoff March 12, 2021). Machine learning models leveraging multimodal data were trained to identify subpopulations of patients who benefit from the addition of tremelimumab to first-line durvalumab and chemotherapy. Results Using clinical and genomic data, the model was able to predict treatment benefit from adding tremelimumab to first-line durvalumab and chemotherapy, with the top ranked 50% of patients with nonsquamous tumors achieving a hazard ratio of 0.56 (95% confidence interval, 0.33-0.97). EGFR wild type, FGFR3 wild type, CDKN2A wild type, KRAS mutations, and STK11 mutations were the factors most associated with higher OS benefit. Conclusions By utilizing machine learning models to analyze POSEIDON data, we yielded genetic signatures identifying patients with nonsquamous metastatic NSCLC who may derive greater OS benefit from the addition of tremelimumab to first-line durvalumab and chemotherapy. Such approaches could be used in the future to enhance precision in tailoring therapies for individual patients.

Ferdinandos Skoulidis, Salma K Jabbour, Edward B Garon, Puneeth Iyengar, Giorgio Scagliotti, Loïc Ferrer, Guillaume Etchepare, Olivier Gallinato, Jérôme Faure, Paul Bernard, Thierry Colin, Philippe Menu, Yian Lin, Ling Cai, Ammar Ahmed Chaudhry, Amanda Remorino, Ross Stewart, Luisa Luciani-Silverman, Katy Miller, David Dellamonica, Jolyon Faria, Yiduo Zhang

The editor's rubric

Heuristic review

Dimension	Level	Weight	What that level means
Leverage	█░░░░ 1	10%	Narrow application of an existing method to a new dataset or setting.
Magnitude	███░░ 3	20%	Large gain: roughly 2x, or a clear new state of the art on a hard, unsaturated problem.
Evidence	█████ 5	32%	Definitive: phase 3 randomized evidence on hard endpoints, multi-lab replication, or community verification at scale.
Novelty	█░░░░ 1	8%	A minor twist on a known approach.
Trajectory	██░░░ 2	5%	Some room to improve with obvious engineering.
Stakes	███░░ 3	25%	Meaningful benefit to many people within a few years.

Editor’s rationale

Heuristic triage from title and abstract text only, not a reading of the paper. Cues found: gains (efficacy, won); design (randomized, phase 3, registered); verification (confidence interval); stakes (mortality, major disease, prevention or cure). Red flags: off-the-shelf model applied to a narrow task; derivative (comparative study).

How the score was computed

rank-2026-10-07

Score█████░░░░░4.8

Score = 10 × (80% × adjusted merit / 10 + 10% × attention + 10% × freshness)

Merit: 6.5 / 10; Weighted rubric, evidence-gated.
Adjusted merit: 5.2 / 10; Shrunk toward the desk prior by editor confidence (50%).
Attention: 0%; Citations, upvotes, points, mentions.
Freshness: 60%; Half-life decay since publication.

Citations0 (reference 20, via openalex, Oct 8, 2026, 06:17 UTC)

The record

Reviewed by heuristic-v5 on Oct 8, 2026, 06:17 UTC. Paper type: clinical.
Categories: Clinical Trial, Phase III, Multicenter Study, Randomized Controlled Trial, Journal Article, Humans, Carcinoma, Non-Small-Cell Lung, Lung Neoplasms, Antineoplastic Combined Chemotherapy Protocols, Antibodies, Monoclonal, Middle Aged
BRIEF, No.6 in the Medicine edition of October 8, 2026.