Genentech’s Double Checkpoint Inhibitor Combo Shows Promise in Lung Cancer

Genentech’s Double Checkpoint Inhibitor Combo Shows Promise in Lung Cancer

Genentech, a Roche company, announced positive results from the Phase II CITYSCAPE clinical trial in PD-L1-positive metastatic non-small cell lung cancer (NSCLC). The study was evaluating a new checkpoint inhibitor tiragolumab and its checkpoint inhibitor Tecentriq (atezolizumab) compared to Tecentriq alone.

Tiragolumab is a novel immunotherapy that binds to TIGIT, an immune checkpoint protein found on immune cells. Tecentriq is a PD-L1 checkpoint inhibitor. Both TIGIT and PD-L1 are involved in immune suppression. Blocking both pathways has the potential for improving anti-tumor activity.

The company plans to present the full data at an oral abstract session of the American Society of Clinical Oncology (ASCO) Virtual Scientific Program being held May 29-31.

“We are pleased to share these first randomized anti-TIGIT results, showing that tiragolumab, our novel cancer immunotherapy, has encouraging efficacy and safety in combination with Tecentriq,” said Levi Garraway, Roche’s chief medical officer and head of Global Product Development. “TIGIT, an immune checkpoint protein expressed on immune cells, was identified by our own scientists. By blocking both TIGIT and PD-L1 pathways simultaneously, we hope to deepen patient responses to immunotherapy and widen the circle of people who may benefit.”

The two-drug combination hit both co-primary endpoints in the intention-to-treat (ITT) population. It showed improvement in objective response rate (ORR) of 31.3% compared to 16.2%, for the combination compared to Tecentriq alone, respectively. And for progression-free survival (PFS), the combo showed a median PFS of 5.4 months compared to 3.6 months for Tecentriq alone.

In patients with high levels of PD-L1, exploratory analysis showed a clinically meaningful improvement in ORR, 55.7% compared to 17.2%, and a 67% decrease in PFS.

The results suggested the combination was well-tolerated with about the same rates of Grade 3 or more all-cause adverse events compared to Tecentriq alone.

TIGIT inhibitors is a new area, with several companies, including Arcus Biosciences, Compugen and Beigene working on therapies.

Although this result is promising, the combination treatment didn’t show as much effectiveness in the broader patient population, instead showing most effectiveness in patients with high PD-L1 levels, but less effectiveness in patients with low PD-L1 levels. In 58 patients with high PD-L1 levels, the combination shrank tumors in more than 50%, while Tecentriq by itself only shrank 17.2% of tumors. In patients with low PD-L1 levels, the combo shrank 13.2% of tumors while shrinking 15.4% in Tecentriq alone.

It is likely more long-term data will be presented at ASCO, which will provide more granularity to the data.

Checkpoint inhibitors, such as Merck’s Keytruda and Bristol Myers Squibb’s Opdivo, have revolutionized certain cancer therapies, but they are not effective in all patients. Which is why there are hundreds, even thousands, of clinical trials testing checkpoint inhibitors in combination with other drugs. Preclinical research has suggested that by blocking both PD-L1 and TIGIT, the therapies can work even better, and for the most part, this Phase II trial supports that idea.

“Anytime you can allow patients to not receive chemotherapy and suffer from side effects … you’re doing patients a service,” Alan Sandler, Genentech’s global head of oncology product development, told FierceBiotech, “particularly if you’re getting the same or better results without the addition of chemotherapy.”

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