FDA gives AbbVie’s c-Met lung cancer ADC a breakthrough tag

by Stephen Riddle

The FDA thinks an antibody-drug conjugate (ADC) developed by AbbVie could set new standards in treatment for certain patients with lung cancer, awarding the drug breakthrough status.

Teliso-V (telisotuzumab vedotin) is pitching to become the first targeted cancer treatment for people with non-small cell lung cancer (NSCLC) whose tumours overexpress c-Met.

The c-Met protein thought to be both a driver of cancer itself, as well as a resistance mechanism that tumours can develop to protect them from some widely-used NSCLC therapies, including EGFR inhibitors.

Teliso-V is currently in a 233-patient phase 2 study (LUMINOSITY) involving subjects with c-Met-positive, non-squamous NSCLC as a second- or third-line treatment after chemotherapy, immunotherapy with checkpoint inhibitors or drugs targeted at specific mutations.

Preliminary results from that study showed a 53.8% overall response rate (ORR) in patients with high levels of c-Met expression, and 25% in those with intermediate levels, showing proof of concept for the ADC.

The FDA reserves breakthrough therapy status for therapies that could represent a significant improvement over standard of care – in this case platinum-based chemotherapy – in either efficacy, safety, or both.

Excluded from that study are patients with EGFR mutations, and AbbVie is looking specifically at this group in a phase 1 study that is looking at the combination of Teliso-V and AstraZeneca’s EGFR inhibitor Tagrisso (osimertinib), to see if the ADC can boost efficacy and potentially reduce the risk of resistance developing.

A phase 3 trial – called TeliMET-NSCLC-01 – is also due to start in the coming months that will compare Teliso-V to docetaxel chemotherapy in c-Met-positive, non-squamous NSCLC, in patients both with and without other gene mutations including EGFR and ALK.

Other drugmakers have been looking at Met as a target in cancer, including Novartis, Merck KgAA and Hutchmed, which have all bagged regulatory approvals for oral therapies that target NSCLC harbouring a specific mutation in Met known as exon 14 skipping  which affects about 3% to 4% of NSCLC patients.

Novartis’ Tepmetko (tepotinib) was approved b the FDA last year for both treatment naïve and previously treated METex14 positive NSCLC patients, as was Merck’s Tabrecta (capmatinib), while Hutchmed’s Orpathys (savolitinib) has been approved as a second-line option in China.

Hutchmed’s drug is also being paired with Tagrisso and AZ’s PD-L1 blocker Imfinzi (durvalumab) in global registrational trials.

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