Gilead Sciences and Arcus are slimming down a phase 3 TIGIT trial to compare the lung cancer combo therapy to just Merck’s Keytruda, ditching a chemotherapy arm.
The move means a little extra cash will be needed to wrap up the trial and meet the enrollment target of 600 patients, but SVB Securities analysts are nevertheless “enthusiastic” about the protocol amendment.
Gilead and Arcus are evaluating the anti-TIGIT domvanalimab plus zimberelimab in a clutch of phase 3 non-small cell lung cancer (NSCLC) studies. One of those three trials, ARC-10, will see the meds compared to just Merck’s standard of care cancer drug Keytruda, instead of chemotherapy. Arcus announced the tweak as part of its third-quarter earnings report Thursday morning.
The strategic protocol amendment was made after discussions with the FDA and will allow for an expansion of the geographical footprint of the trial. Arcus said the change “addresses the importance, both clinically and commercially” of using a widely accepted standard of care as a comparator amid a shifting U.S. regulatory landscape for cancer drugs.
“The optimization of our phase 3 ARC-10 study design and the initiation of the fourth phase 3 registrational study for domvanalimab position Arcus to leverage the full potential of domvanalimab,” Arcus CEO Terry Rosen, Ph.D., said.
Previously, the trial compared domvanalimab plus zimberelimab to zimberelimab, and zimberelimab to chemotherapy. The new protocol is much simpler and reduces the number of arms from three to two, while leaving the trial size the same at 600 patients. By eliminating the chemo arm and bringing in Keytruda, Arcus can establish sites in the U.S. and other countries previously unavailable based on the criteria. Overall survival will be the primary endpoint.
The companies are aiming to take on king Keytruda and create a new standard of care anti-TIGIT/anti-PD-(L)1 regimen in multiple settings, according to Rosen.
Arcus will also add a fourth phase 3 trial to the series. The entire late-stage program aims to “establish the potential benefit of domvanalimab in a broad spectrum of NSCLC settings,” Arcus said.
The TIGIT field is being closely watched by analysts after Roche’s tiragolumab failed to demonstrate progression-free survival in patients with small cell lung cancer during a phase 3 trial earlier this year. Arcus and Gilead have taken a slightly different approach with their therapy combo, but SVB Securities senior research analyst Daina Graybosch, Ph.D., told Fierce Biotech in May that data are needed to confirm the TIGIT hypothesis.
SVB Securities is expecting the most impactful TIGIT catalysts to arrive in 2023, including data from Gilead and Arcus’ ARC-7 study and an update from Roche’s SKYSCRAPER-01 trial in NSCLC.
Arcus said the ARC-7 data, which are examining another TIGIT therapy, etrumadenant, plus zimberelimab in metastatic castrate-resistant prostate cancer, is expected “in-house” by the end of the year with presentation in 2023. Data from ARC-9 featuring various etrumadenant-based combinations in metastatic colorectal cancer are expected in the first half as well.
Gilead and Arcus’ 10-year partnership includes etrumadenant, domvanalimab, quemliclustat and zimberelimab. Gilead pays $150 million per program opt-in and has taken a $200 million equity investment in Arcus. The deal was amended in February 2021 with Gilead adding an additional $220 million investment and increasing its stake to 19.5%. The companies are co-developing the assets and share global development costs.
Arcus reported cash, cash equivalents and marketable securities of $1.191 billion as of Sept. 30, 2022, thanks in part to $725 million paid by Gilead in January 2022. This cash should fund operations into 2026, according to Arcus’ earnings report.