The big gamble that Pfizer made on antibody-drug conjugates (ADCs) has gone sour.The pharma giant revealed that its first new ADC product since it paid $43 billion for Seagen, sigvotatug vedotin, has faltered in a phase 3 study of lung cancer.
It was shown that the potential first-in-class ADC was not able to significantly improve overall survival (OS) when compared with the chemotherapy docetaxel in patients with previously treated nonsquamous NSCLC (Be6A Lung-01 or SigVie-002), thus failing to meet the primary endpoint of the study.
“In addition to the data from this phase 3 trial, the newest phase 1 data reinforces our belief that the sigvotatug vedotin program has significant promise for advancing the treatment of patients with OS and progression-free survival in a subpopulation of patients who received one prior line of therapy,” Pfizer’s chief oncology officer, Jeff Legos, said in a June 22 release.
Sigvotatug is directed towards the integrin beta-b (IB6) that is present in almost 90% of NSCLC tumors. In its press release, Pfizer said an exploratory analysis of the SigVie-002 trial found no clear relationship between IB6 expression and patient response.
As he noted, he remains confident in the program, given that it is being tested in a phase 3 study called Lung-02 with the combination of sigvotatug vedotin and Merck & Co.’s Keytruda in patients with first-line NSCLC with high PD-L1 expression.
“The capacity of sigvotatug vedotin to deliver immunogenic cell death offers significant potential for combination treatment with immunotherapies, especially in earlier treatment lines when immune function is still intact,” said lead investigator of Pfizer’s sigvotatug vedotin trial program, Solange Peters, from Lausanne University Hospital in Switzerland.
The most recent failure further raises doubts about Pfizer’s capacity to deliver further products to the market in the ADC space beyond its current commercial products, Seagen. Pfizer also eliminated a B7-H4 ADC one year ago after the acquisition and has dramatically scaled back research on HER2 ADC disitamab vedotin, which it has partnered with RemeGen on.
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.
Legos noted that Pfizer is working on next-generation ADCs with “a variety of permutations” – new targets, antibody structures and payloads. Of these, Pfizer is testing another IB6 candidate, which has a Topo1 payload, against the MMAE payload in sigvotatug vedotin.
The company is also testing sigvotatug vedotin in new combinations, such as its newly acquired PD-1xVEGF bispecific antibody, PF-08634404, another hot new space in drug development for first-line NSCLC.
In addition, fetrastobart vedotin (PF-08046054), an ADC targeting PD-L1, is also in a phase 3 trial in previously treated NSCLC, Pfizer said in its June 22 release.
Pfizer has announced that it plans to have at least eight blockbuster cancer treatments by 2030 in a roadmap that was revealed after the company’s buyout.
Pfizer has announced that a Phase 3 clinical trial evaluating its first novel antibody-drug conjugate (ADC) obtained through the acquisition of Seagen failed to meet its primary endpoint in patients with non-small cell lung cancer (NSCLC). The outcome represents a setback for Pfizer as it continues to expand its oncology portfolio following the multibillion-dollar Seagen acquisition.
Although disappointing, Pfizer emphasized that it will continue analyzing the trial data to better understand the results and determine the future development strategy for the investigational therapy.
Pfizer’s Oncology Strategy Faces a Clinical Setback
The ADC program was viewed as one of the key assets supporting Pfizer’s long-term oncology ambitions after acquiring Seagen, a leader in antibody-drug conjugate technology. The unsuccessful Phase 3 trial highlights the challenges of late-stage cancer drug development, where promising early results do not always translate into successful pivotal studies.
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