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Record W4406104381 · doi:10.1038/s41591-024-03334-7

Autogene cevumeran with or without atezolizumab in advanced solid tumors: a phase 1 trial

2025· article· en· W4406104381 on OpenAlexaff
Juanita Lopez, Thomas Powles, Fadi Braiteh, Lillian L. Siu, Patricia LoRusso, Claire F. Friedman, Ani Sarkis Balmanoukian, Michael Gordon, Jeffrey Yachnin, Sylvie Rottey, Ioannis Karydis, George A. Fisher, Marcus Schmidt, Martin Schüler, Ryan J. Sullivan, Howard A. Burris, Vladimir Galvao, Brian S. Henick, Luc Dirix, Dirk Jaeger, Patrick A. Ott, Kit Man Wong, Guy Jérusalem, Aglaia Schiza, Lawrence Fong, Neeltje Steeghs, Rom S. Leidner, Achim Rittmeyer, Scott A. Laurie, Eelke Gort, Raid Aljumaily, Ignacio Melero, Rachel Lubong Sabado, Ina Rhee, Michael R. Mancuso, Lars Müller, Gregg Fine, Mahesh Yadav, Leesun Kim, Vincent J. P. Leveque, Alberto Robert, Martine Darwish, Ting Qi, Jiawen Zhu, Jingbin Zhang, Patrick Twomey, Gautham K. Rao, Christoph Petry, Jill Schartner, Lélia Delamarre, Ira Mellman, Martin Löwer, Felicitas Müller, Evelyna Derhovanessian, Andrea Cortini, Luisa Manning, Daniel Maurus, Sebastian Brachtendorf, Verena Lörks, Tana Omokoko, Eva Godehardt, Dirk Becker, Christine Hawner, Christine Wallrapp, Christian Albrecht, Christoph Kröner, Arbel D. Tadmor, Jan Diekmann, Mathias Vormehr, Anette Jork, Anna Paruzynski, Maren Lang, Jonathon Blake, Oliver Hennig, Andreas N. Kuhn, Uğur Şahin, Özlem Türeci, D. Ross Camidge

Bibliographic record

VenueNature Medicine · 2025
Typearticle
Languageen
FieldImmunology and Microbiology
TopicImmunotherapy and Immune Responses
Canadian institutionsOttawa HospitalPrincess Margaret Cancer Centre
FundersHelen Diller Family Comprehensive Cancer Center, University of California, San FranciscoNational Center for Advancing Translational SciencesCancer Center, University of ColoradoUniversity of California, San FranciscoQueen Mary University of LondonWeill Cornell Medical CollegeGenentechCentro de Investigación Biomédica en Red de CáncerUniversidad de NavarraMemorial Sloan-Kettering Cancer CenterUniversity of WashingtonUppsala UniversitetUniversiteit GentJohannes Gutenberg-Universität MainzUniversity of Oklahoma Health Sciences CenterUniversitair Ziekenhuis GentUniversity of SouthamptonSeagenAkademiska SjukhusetCedars-Sinai Medical CenterUniversity of OklahomaMassachusetts General HospitalNational Cancer InstituteGilead SciencesYale UniversityUniversity Hospital Southampton NHS Foundation TrustDeutsches KrebsforschungszentrumUniversitätsmedizin der Johannes Gutenberg-Universität MainzYale Cancer Center
KeywordsAtezolizumabMedicineImmunogenicityTolerabilityImmunotherapyCD8OncologyInternal medicineImmunologyCancerImmune systemPembrolizumabAdverse effect

Abstract

fetched live from OpenAlex

Abstract Effective targeting of somatic cancer mutations to enhance the efficacy of cancer immunotherapy requires an individualized approach. Autogene cevumeran is a uridine messenger RNA lipoplex-based individualized neoantigen-specific immunotherapy designed from tumor-specific somatic mutation data obtained from tumor tissue of each individual patient to stimulate T cell responses against up to 20 neoantigens. This ongoing phase 1 study evaluated autogene cevumeran as monotherapy ( n = 30) and in combination with atezolizumab ( n = 183) in pretreated patients with advanced solid tumors. The primary objective was safety and tolerability; exploratory objectives included evaluation of pharmacokinetics, pharmacodynamics, preliminary antitumor activity and immunogenicity. Non-prespecified interim analysis showed that autogene cevumeran was well tolerated and elicited poly-epitopic neoantigen-specific responses, encompassing CD4 + and/or CD8 + T cells, in 71% of patients, most of them undetectable at baseline. Responses were detectable up to 23 months after treatment initiation. CD8 + T cells specific for several neoantigens constituted a median of 7.3% of circulating CD8 + T cells, reaching up to 23% in some patients. Autogene cevumeran-induced T cells were found within tumor lesions constituting up to 7.2% of tumor-infiltrating T cells. Clinical activity was observed, including one objective response in monotherapy dose escalation and in two patients with disease characteristics unfavorable for response to immunotherapy treated in combination with atezolizumab. These findings support the continued development of autogene cevumeran in earlier treatment lines. ClinicalTrials.gov registration: NCT03289962 .

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Randomized trial · Consensus signal: Randomized trial
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.235
Threshold uncertainty score0.987

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0000.001
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0010.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.009
GPT teacher head0.340
Teacher spread0.330 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designRandomized trial
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations96
Published2025
Admission routes1
Has abstractyes

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