ALX Oncology sees a future for its beleaguered anti-CD47 drug in solid tumors. The biotech reported a 52% response rate in recipients of the therapy, compared to 22% in the control arm, leading it to sketch out a future for the asset in patients who progress after receiving drugs such as Enhertu and Keytruda.
San Francisco-based ALX stopped a pair of blood cancer clinical trials of its CD47-blocking fusion protein, evorpacept, in August, further dampening expectations for a mechanism of action that was among the most hyped in oncology before a series of setbacks took the shine off. But, while the blood cancer data from multiple assets have disappointed, ALX and its rival Gilead Sciences have continued to go after solid tumors.
ALX now has data to support the continuation of its solid tumor program. Interim phase 2 results linked the addition of evorpacept to trastuzumab, Eli Lilly’s Cyramza and paclitaxel to a higher response rate in HER2-positive advanced gastric/gastroesophageal junction (G/GEJ) patients.
The study randomized 54 patients with second and third-line G/GEJ to receive trastuzumab, Cyramza and paclitaxel or that three-drug regimen plus evorpacept. As well as linking the use of evorpacept to a 30 percentage point higher objective response rate (ORR), ALX saw early evidence of durability. The median duration of response was 7.4 months in the control and is yet to be reached in the evorpacept arm.
The response rate in the control arm is lower than the efficacy seen in other studies of the drugs. Earlier this year, an open-label trial linked the second-line use of trastuzumab, ramucirumab and paclitaxel to a 54% ORR in 50 HER2-positive advanced G/GEJ cancer patients. And ramucirumab and paclitaxel, without trastuzumab, had a 28% ORR in a study ALX called the regulatory benchmark and global standard of care.
Comparing data between the studies is complicated by differences between the trials. ALX hailed its trial as the first global randomized study in HER2-positive gastric cancer that accepted participants who had previously taken Merck & Co.’s Keytruda and AstraZeneca and Daiichi Sankyo’s Enhertu. The biotech said a “meaningful” number of participants had previously received Enhertu and checkpoint inhibitors.
The responses in previously treated patients suggests there may be a role for evorpacept in people who progress after first-line therapy. ALX will work to validate that idea over the coming years, first by posting the final analysis from the phase 2 study in the second quarter of 2024 and then by starting the phase 3 portion of the trial.
ALX plans to start the phase 3 trial in the second half of next year, a six-month window that is shaping up to be a key early test of the biotech’s solid tumor plans. In that window, ALX plans to report data from two phase 2 trials in head and neck squamous cell carcinoma and from phase 1b studies in urothelial carcinoma and breast cancer.