AbbVie’s lung cancer data light path to ADC accelerated approval but fall short of earlier benchmark

AbbVie has its eyes on accelerated approval of its c-Met antibody-drug conjugate (ADC). The candidate achieved a 35% response rate in a subset of lung cancer patients, spurring plans to talk to regulators, but unfavorable comparisons to an earlier data drop partly took the shine off the update.

In the Luminosity trial, AbbVie gave its ADC telisotuzumab-vedotin (Teliso-V) to patients with epidermal growth factor receptor (EGFR) wild type, advanced/metastatic nonsquamous non-small cell lung cancer (NSCLC). The tumors overexpressed c-Met, a protein that is found at elevated levels in around 25% of people with advanced EGFR wild type NSCLC.

AbbVie split its analysis between patients with high and intermediate c-Met expression. In the c-Met high group, the Big Pharma linked Teliso-V to an overall response rate of 35%. The response rate fell to 23% in the c-Met intermediate cohort. AbbVie's Chief Medical Officer Roopal Thakkar, M.D., has previously said the targeted population is split evenly between c-Met high and c-Met intermediate patients.

The response rates are down on the results AbbVie shared at the start of last year. That earlier update, which secured a breakthrough designation for Teliso-V, linked the ADC to response rates of 53.8% and 25.0%, respectively, in c-Met high and c-Met intermediate patients. AbbVie now has durability data, reporting median overall survival of 14.6 months in c-Met high and 14.2 months in c-Met intermediate.

With no new safety concerns emerging, AbbVie plans to talk to authorities about seeking accelerated approval. A phase 3 trial that could support full approval down the line is already underway. If Teliso-V comes to market, the ADC would become the first drug approved for use in the patient population.

While AbbVie’s focus on patients with c-Met overexpression, EGFR wild type NSCLC sets it apart, it still has to contend with comparisons to other medicines, notably Johnson & Johnson’s bispecific antibody Rybrevant. The drug, which targets EGFR and MET, has accelerated approval in NSCLC with EGFR exon 20 insertion mutations. 

Thakkar discussed the competitive landscape on a quarterly results call with investors in late October when he reflected on data that other companies shared at the European Society of Medical Oncology 2023 Congress. The AbbVie executive made the case that safety could give Teliso-V an advantage.

“If you look at EGFR mutants in lungs, you see some higher levels of efficacy, either in the frontline or second line in that space, but that comes at a cost,” the CMO said. “And that's a chemo-like adverse event profile. Those are things like nausea, vomiting, stomatitis, alopecia, [and] fatigue. You may see slight increases in efficacy. But clearly, patients don't want that.”