Anetumab ravtansine
Anetumab ravtansine was the first antibody-drug conjugate tested in a randomised trial in mesothelioma, aimed at the mesothelin protein that nearly all mesotheliomas carry; it was no better than vinorelbine chemotherapy as second-line treatment, and is now being tried with pembrolizumab.
Overview
Bayer built anetumab ravtansine around mesothelin, a surface protein over-expressed in mesothelioma, ovarian, pancreatic and some lung cancers but scarce in normal tissue. In the 248-patient randomised phase 2 trial in relapsed, mesothelin-positive pleural mesothelioma after platinum and pemetrexed, median progression-free survival was 4.3 months with anetumab ravtansine against 4.5 months with vinorelbine (hazard ratio 1.22), with far less neutropenia but corneal and other toxicities, so development for mesothelioma as a single agent stopped. A National Cancer Institute phase 1/2 trial is testing it with pembrolizumab, and the drug remains the reference case for why mesothelin-directed conjugates have struggled: shed mesothelin in the blood soaks up antibody, expression is heterogeneous, and a tubulin payload adds little to a slow-growing tumour that already resists chemotherapy.
A fully human anti-mesothelin antibody linked through a disulfide linker to the maytansinoid tubulin inhibitor DM4; binding to mesothelin on the tumour cell surface internalises the conjugate and releases the payload. Connects to Mesothelin.
1.Anetumab ravtansine's antibody arm binds Mesothelin on the surface of the cancer cell.
- AmivantamabApproved
- CamizestrantApproved
- Comprehensive genomic profilingStandard of care
- Liquid biopsy (ctDNA)Standard of care
- LorlatinibApproved
- MRD / molecular residual disease testingEstablished
- ADC payload neutralisersPhase 1
- BGB-16673Phase 3
- Bispecific ADCPhase 3
- BRUIN CLL-321Positive
- CaDAnCe-304Recruiting
- CIRCULATE-Japan (GALAXY / VEGA / ALTAIR)Active
- A clone report from blood at every treatment cycle
- A fast route to the matched drug when it is licensed for another cancer
- A multi-cancer platform trial of adaptive (dose-holiday) therapy
- A national rapid research autopsy network for end-stage cancer
- A standard evolvability score for every tumour
- A standing platform trial that assigns treatment by how the tumour escaped
Background: ADC sequencing, Antigen escape (antigen loss, lineage switch), BCG-unresponsive, Castration-resistant prostate cancer (CRPC), Circulating tumour DNA (ctDNA). Also on OnCo: Resistance atlas · Lines of therapy.
Trials
topTrials recruiting now
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Landmark trials
Latest papers
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Similar pages
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