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A Phase I Dose Escalation and Cohort Expansion Study of CB307, a Trispecific Humabody against PSMA, CD137, and Albumin in Patients with PSMA-Positive Solid Tumors

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dc.contributor.authorde Bon, Johann S.
dc.contributor.authorWilliams, Anja
dc.contributor.authorMelero, Ignacio
dc.contributor.authorJayaram, Anuradha
dc.contributor.authorHawley, Jessica E.
dc.contributor.authorde Speville, Bernard Doger
dc.contributor.authorMoreno, Irene
dc.contributor.authorCastellano, Daniel
dc.contributor.authorReig, Oscar
dc.contributor.authorKnapen, Daan G.
dc.contributor.authorAnguera, Georgia
dc.contributor.authorMartínez, Julia
dc.contributor.authorGort, Eelke
dc.contributor.authorde Jonge, Maja
dc.contributor.authorAlonso Romero, José Luis
dc.contributor.authorBoni, Valentina
dc.contributor.authorPérez Gracia, Jose Luis
dc.contributor.authorFalcon, Alejandro
dc.contributor.authorde Groot, Derk Jan
dc.contributor.authorPierce, Andrew J.
dc.contributor.authorLeishman, Andrew J.
dc.contributor.authorLloyd, Peter
dc.contributor.authorBartlett, Phillip D.
dc.contributor.authorBland-Ward, Philip
dc.contributor.authorChau, Albert
dc.contributor.authorSong, Minjung
dc.contributor.authorDuffy, Kevin
dc.contributor.authorHashimoto, Kenji
dc.contributor.authorde Vries, Eisabeth
dc.contributor.departmentMedicina
dc.contributor.otherFacultades de la UMU::Facultad de Medicina
dc.date.accessioned2026-03-25T11:46:16Z
dc.date.available2026-03-25T11:46:16Z
dc.date.copyright©2025 American Association for Cancer Research
dc.date.issued2025-08-15
dc.description.abstractPurpose: CB307 is a trispecific variable heavy-chain antibody fragment against prostate-specific membrane antigen (PSMA), CD137, and human serum albumin. It is designed to mitigate hepatotoxicity by activating T cells only in PSMA-positive tumors and to increase drug half-life through albumin binding. This phase I study investigated the safety and tolerability of CB307 as monotherapy or in combination with pembrolizumab. Patients and Methods: Patients who were heavily pretreated with PSMA-positive solid tumors were enrolled in the dose-escalation phase of CB307 monotherapy. The additional safety and efficacy of CB307 were assessed in the CB307 monotherapy expansion cohort and in combination with pembrolizumab. Results: CB307 was administered to 75 patients. CB307 was given once every 7 days as monotherapy (N = 50) or in combination with pembrolizumab (N = 25). Two dose-limiting toxicities (grade 3 transient transaminitis) were observed. A total of three grade 3 transaminitis events (one in the monotherapy cohort and two in the combination cohort) were observed, and none involved bilirubin elevation. Durable RECIST responses were observed in two patients with metastatic castration-resistant prostate cancer enrolled in the 800 mg CB307 monotherapy and in one patient in the combination cohort (overall response rates: 11.1% and 7.1%, respectively). A disease control rate (DCR) of 50% was observed in patients enrolled in the 800 mg CB307 monotherapy cohort and 42.9% in the combination cohort. In a post hoc analysis, the response was numerically better in patients who had not received chemotherapy in the 6 months prior to starting CB307 (ORR = 20%, DCR = 60% vs. ORR = 0%, DCR = 37.5%). CB307 induces cytotoxic cell expansion in tumors and PD-L1 expression. Conclusions: CB307 was well tolerated as a monotherapy and in combination with pembrolizumab, and tumor responses were observed in patients with metastatic castration-resistant prostate cancer.
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dc.identifier.citationde Bono, J. S., Williams, A., Melero, I., Jayaram, A., Hawley, J. E., Doger de Speville, B., ... & de Vries, E. (2025). A phase I dose escalation and cohort expansion study of CB307, a trispecific humabody against PSMA, CD137, and albumin in patients with PSMA-positive solid tumors. Clinical Cancer Research, 31(16), 3388-3399.
dc.identifier.doihttps://doi.org/10.1158/1078-0432.CCR-24-3581
dc.identifier.eissn1557-3265
dc.identifier.issn1078-0432
dc.identifier.urihttp://hdl.handle.net/10201/222821
dc.languageeng
dc.publisherAmerican Association for Cancer Research
dc.relationSin financiación externa a la Universidad
dc.relation.publisherversionhttps://aacrjournals.org/clincancerres/article-abstract/31/16/3388/763987/A-Phase-I-Dose-Escalation-and-Cohort-Expansion
dc.rights.accessRightsinfo:eu-repo/semantics/restrictedAccess
dc.subject.odsObjetivo 3: Salud
dc.titleA Phase I Dose Escalation and Cohort Expansion Study of CB307, a Trispecific Humabody against PSMA, CD137, and Albumin in Patients with PSMA-Positive Solid Tumors
dc.typeinfo:eu-repo/semantics/article
dc.type.versioninfo:eu-repo/semantics/publishedVersion
dspace.entity.typePublicationes
relation.isAuthorOfPublication79c9c691-9c36-4057-91b8-cf928d76847b
relation.isAuthorOfPublication.latestForDiscovery79c9c691-9c36-4057-91b8-cf928d76847b
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