Pfizer’s first new ADC from Seagen acquisition fails phase 3 NSCLC trial
By Angus Liu Jun 23, 2026 7:15am
Pfizer antibody-drug conjugates non-small cell lung cancer Seagen
Despite the miss, Pfizer expressed confidence in the potential of sigvotatug vedotin in first-line NSCLC. (Angus Liu/Fierce Pharma)
Pfizer’s high-stakes bet on antibody-drug conjugates (ADCs) has hit a speed bump.
The pharma giant announced Monday that sigvotatug vedotin, the first new ADC to read out pivotal data following its $43 billion acquisition of Seagen, has stumbled in a phase 3 lung cancer study.
The potential first-in-class ADC failed to significantly improve overall survival (OS) compared with docetaxel chemotherapy in patients with previously treated nonsquamous NSCLC, causing the phase 3 SigVie-002 trial, also known as Be6A Lung-01, to miss its primary endpoint.
However, pointing to a “stronger trend” for OS and progression-free survival in a subgroup of patients who received only one prior line of therapy, Pfizer’s chief oncology officer, Jeff Legos, Ph.D., said the readout, along with additional phase 1 data, “reinforces our confidence in the potential of the sigvotatug vedotin program, including an ongoing phase 3 trial in combination with pembrolizumab in first-line advanced NSCLC,” according to a June 22 statement.
Sigvotatug vedotin is designed to target integrin beta-b (IB6), which is expressed on approximately 90% of NSCLC tumors. In its Monday press release, Pfizer said an exploratory analysis of the SigVie-002 trial found no clear relationship between IB6 expression and patient response.
Meanwhile, the phase 3 Be6A Lung-02 trial, which Legos referenced regarding his continued confidence in the program, is evaluating the combination of sigvotatug vedotin and Merck & Co.’s Keytruda in patients with first-line NSCLC who have high levels of PD-L1 expression.
“The ability of sigvotatug vedotin to induce immunogenic cell death provides a strong rationale for combination approaches with immunotherapy, particularly in earlier treatment settings where immune competence is better preserved,” Solange Peters, M.D., Ph.D., from Lausanne University Hospital in Switzerland and a lead investigator in Pfizer’s sigvotatug vedotin trial program, said in a statement.
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The latest trial setback once again brings into question Pfizer’s ability to bring forth additional ADCs beyond Seagen’s existing commercial offerings. Since the acquisition, Pfizer discontinued a B7-H4 ADC a year ago and has repeatedly pared back efforts around its RemeGen-partnered HER2 ADC disitamab vedotin.
Earlier this year, the New York pharma pruned PF-08046031, an ADC that targets CD228, and scrapped PF-08046037, which, instead of a cytotoxic payload, uses a TLR7 agonist as an immunostimulatory payload.
Still, in an interview with Fierce early this year, Legos said Pfizer is actively designing next-generation ADCs with “a variety of permutations,” including new targets, antibody constructs and novel payloads. Among them, Pfizer is testing another IB6 candidate with a Topo1 payload, versus the MMAE payload used in sigvotatug vedotin.
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The company is also exploring sigvotatug vedotin in novel combinations, including with its newly acquired PD-1xVEGF bispecific antibody, PF-08634404, which represents another hot frontier in drug development for first-line NSCLC.
What’s more, fetrastobart vedotin (PF-08046054), a PD-L1-directed ADC, is also in phase 3 trial in previously treated NSCLC, Pfizer noted in its June 22 release.
In a roadmap unveiled after the Seagen buyout, Pfizer said it is targeting at least eight blockbuster cancer drugs by 2030.
Pfizer antibody-drug conjugates non-small cell lung cancer Seagen lung cancer Clinical Data Biotech
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