Presentations at this year’s American Association for Cancer Research meeting could have a broad impact on the treatment landscape for head and neck and lung cancer, and implications for specific drug modalities like TIGIT and VEGF.
On Friday, the streets of Chicago, Illinois—or at least, the halls of its McCormick Place Convention Center—will flood with hundreds of cancer experts from across the country. The annual meeting of the American Association for Cancer Research is in town and will host some of the most cutting-edge research in oncology.
Expectations are great for this year’s event, which will host a few highly impactful readouts, some of which could have far-reaching implications for the market and for clinical practice.
One of the most anticipated presentations is a detailed readout for Merck’s Phase III KEYNOTE-689 study, which evaluated its blockbuster PD-1 blocker Keytruda in head and neck squamous cell carcinoma (HNSCC).
In October 2024, the pharma provided a topline peek at the study’s results, noting that Keytruda elicited a “statistically significant and clinically meaningful improvement” in event-free survival and a “trend toward improvement” in overall survival. Merck did not provide specific data at the time, and Keytruda’s magnitude of efficacy in this indication remains unknown.
However, in an April 16 note to investors, William Blair analysts said they expect KEYNOTE-689 to have “read-through to the broader” HNSCC treatment space.
“Merck’s Keynote-689 will have some impact on the head and neck cancer landscape/market opportunity,” William Blair analyst Matt Phipps added in an email to BioSpace. Detailed findings from the trial will likely affect other players in this space, including Merus and its bispecific antibody petosemtamab, and Exelixis, which is advancing its oral tyrosine kinase inhibitor zanzalintinib, according to Phipps.
Aside from HNSCC, AACR 2025 could also witness big readouts in lung cancer. In an email to BioSpace, AACR president-elect Lillian Siu, a senior medical oncologist at the Princess Margaret Cancer Centre in Toronto, pointed to Boehringer Ingelheim’s Beamion LUNG-1 trial, which she said could be “practice-changing.”
The trial is studying the HER2 tyrosine kinase blocker zongertinib in non-small cell lung cancer (NSCLC). A Phase Ib readout in September 2024 demonstrated a 66.7% objective response rate for zongertinib, which also shrank tumors in 94% of treated patients. Boehringer Ingelheim is scheduled to release additional findings from Beamion LUNG-1 on Monday.
Modality Movement
Beyond specific indications, many experts also expect this year’s AACR cycle to be critical for certain treatment modalities.
“VEGF-PD(L)1 bispecifics took the oncology world by storm” in September last year, when Summit Therapeutics and Akeso announced that their investigational bispecific antibody ivonescimab bested Keytruda as a frontline NSCLC treatment, Christiana Bardon, co-managing partner at biotech investment firm MPM BioImpact, told BioSpace in an email.
The oncology partners doubled down on those results on Wednesday, reporting that the candidate yielded better progression-free survival than BeiGene’s PD-1 inhibitor Tevimbra in patients with NSCLC.
“Since [September 2024], a wave of VEGF bispecifics and some trispecifics have emerged,” according to Bardon, who noted that at least 13 of these, including ivonescimab and a candidate developed by Hangzhou DAC Biotechnology and dubbed DXA023-G017, will have data at AACR. “There’s even a VEGF bispecific with an [antibody-drug conjugate] payload,” she said.
Bardon is quick to caution, however, that assets playing in this space “are still mostly at the preclinical stage.” Nevertheless, “they have the potential to disrupt the oncology landscape if successful.”
William Blair’s Phipps, for his part, is focused on the TIGIT space, which in recent months has been battered by setbacks. Last month, for instance, BeiGene was forced to scrap its TIGIT asset ociperlimab after disappointing late-stage data, which showed that the candidate was “unlikely to meet the primary endpoint of overall survival” in the Phase III AdvanTIG-302 trial in NSCLC.
However, arguably the most high-profile defeat belongs to Roche, which in November 2024 reported that its anti-TIGIT antibody tiragolumab failed the SKYSCRAPER-01 study in locally advanced unresectable or metastatic NSCLC, unable to significantly improve overall survival versus placebo.
The pharma did not provide specific data at the time, but will do so at AACR. A more comprehensive readout “will have important implications for the TIGIT inhibitor space,” Phipps said. “We know the trial failed, but are there reasons that can be gleaned that might allow others to still succeed with this target?”
Among these other players are partners Gilead and Arcus, which in November 2024 reported Phase III data showing that their anti-TIGIT antibody domvanalimab, when combined with the PD-1 therapy zimberelimab, significantly boosted progression-free and overall survival in patients with a specific type of NSCLC, as compared with zimberelimab or chemotherapy.
The partners are also trialing the domvanalimab-zimberelimab combo in HSNCC, for which they are scheduled to present mid-stage data at AACR.
