Pfizer delivers ‘disappointing’ late-stage lung cancer data for ADC from $43B Seagen buy

 

Despite an overall survival miss, Leerink Partners said Pfizer’s antibody-drug conjugate showed “promising” signals of efficacy in a subgroup of patients who had undergone only one prior line of treatment.

Pfizer’s highly watched investigational antibody-drug conjugate failed to significantly improve overall survival in a Phase 3 study of non-small cell lung cancer. Multiple analyst groups called the findings “disappointing,” but the pharma will nevertheless continue to test the asset in this indication and for other solid tumors.

Without revealing specific data, Pfizer said in a Monday release that sigvotatug vedotin, which the pharma acquired through its $43 billion takeover of Seagen in 2023, did not elicit statistically significant overall survival (OS) benefits in the Phase 3 SigVie-002 study of patients with unresectable or metastatic non-squamous non-small cell lung cancer (NSCLC).

The trial focused on participants who had undergone one or more prior lines of treatment. However, in a subgroup of patients with only one such line of previous systemic exposure, Pfizer reported a “stronger trend” of OS and progression-free survival in favor of the antibody-drug conjugate (ADC) over the chemotherapy docetaxel.

Leerink Partners said the results of the subgroup analysis are “promising.” Sigvotatug vedotin, the firm continued, “still has a chance to succeed in combination with pembrolizumab”—Merck’s blockbuster PD-1 inhibitor marketed as Keytruda—in a separate NSCLC study positioning the combo regimen as a first-line option.

Indeed, Pfizer on Monday said that despite failing SigVie-002, it will continue several studies of the ADC, including the one testing the Keytruda regimen. Another trial exploring other combinations of sigvotatug vedotin—including using it with a PD-1/VEGF bispecific antibody—will also move forward.

Sigvotatug vedotin targets the integrin beta-6 protein, which is expressed in around 90% of NSCLC tumors, according to the pharma. By binding its target, the ADC is able to deliver its cancer-killing payload with high specificity, potentially minimizing side effects.

Like Leerink, Guggenheim Securities analysts were “disappointed” by the Monday readout, though they had been expecting the outcome. “We are disappointed but not surprised by the result given how difficult it has been for other agents to show an OS benefit over docetaxel,” the firm wrote.

In a March 27 note previewing the SigVie-002 results, the firm pointed to another example: AstraZeneca’s datopotamab deruxtecan. In May 2024, the asset failed to significantly top docetaxel’s OS improvements in the Phase 3 TROPION-Lung01 study of locally advanced or metastatic NSCLC. The drug, now called Datroway, has since been approved for the indication based on progression-free survival data.

https://www.biospace.com/drug-development/pfizer-delivers-disappointing-late-stage-lung-cancer-data-for-adc-from-43b-seagen-buy