Where's the next cancer mega-blockbuster?

Keytruda, an anti-PD-1 antibody, has become one of oncology’s defining commercial and clinical success stories, generating more than $30 billion in annual revenue and serving as a cornerstone treatment across dozens of cancer settings. But even the largest franchises face an expiration date. With Keytruda expected to begin losing patent exclusivity in 2029, investors are increasingly focused on whether oncology will see another therapy with comparable breadth and commercial scale. No single pipeline asset appears likely to match Keytruda’s impact on its own, but emerging approaches such as PD-1/VEGF bispecific antibodies and antibody-drug conjugates could extend — and potentially expand — the treatment paradigms established by PD-1 inhibitors.

Both combine multiple anti-cancer mechanisms that may produce synergistic benefits. The PD-1/VEGF strategy seeks not only to improve outcomes in established immuno-oncology settings but also to expand into tumors where VEGF inhibition is already a standard component of care. The commercial opportunity is significant, but so is the competition. Oncology has historically been a first-mover market where clinical differentiation matters, and leadership positions can be difficult to displace. Trial design and execution will be critical with this new class, especially for those companies that are not at the forefront when it comes to advancing their PD-1/VEGF bispecific agents into pivotal studies.  

One particularly promising partner for an immuno-oncology backbone — whether a PD-1/VEGF bispecific or a traditional PD-1 agent — is the antibody-drug conjugate, or ADC class. ADCs are designed to deliver potent chemotherapy directly to cancer cells, creating the potential for improved efficacy with comparable or better tolerability than conventional chemotherapy. Merck is among several pharma companies building a late-stage ADC portfolio, and sacituzumab tirumotecan (sac-TMT), a TROP2-targeted ADC, has emerged as a notable candidate. The agent has demonstrated encouraging efficacy across multiple tumor types, suggesting a breadth of activity.  

The next 6–12 months could prove important for understanding how these oncology approaches intersect, particularly in the large lung cancer market. Recent results from the China-based Phase 3 OptiTROP-Lung05 and Lung06 studies have helped de-risk sac-TMT in a range of settings, but global studies remain necessary to support broader adoption in developed markets. Key questions remain: Can sac-TMT outperform standard chemotherapy on its own? Is combining it with Keytruda sufficient, or could a PD-1/VEGF backbone create additional value? And what level of efficacy will ultimately be required to differentiate in an increasingly competitive lung-cancer landscape? Upcoming detailed data from Merck’s OTL-06 study, Summit’s HARMONi-3 trial and AstraZeneca’s AVANZAR program should provide valuable context.