BARCELONA — In a first test of Scorpion Therapeutics’ therapy for breast cancer and other solid tumors, a small group of patients saw their tumors shrink following treatment with no severe cases of toxicities like high blood sugar and diarrhea that have plagued the experimental drug’s predecessors.
Scorpion, which announced a $150 million Series C raise in July, is developing an inhibitor for PI3Kα, a common cancer driver that’s found across a range of tumors. The Boston-based biotech is competing with a number of biopharma companies, including Novartis and Roche, which have developed drugs for PIK3CA-mutated breast cancer. The PIK3CA gene codes a part of the PI3Kα kinase.
In the first cut of Scorpion’s trial data, disclosed in a late-breaking presentation on Sunday at the European Society for Medical Oncology annual meeting in Barcelona, nine of 43 patients with certain PIK3CA mutations saw their tumors shrink at least 30% after treatment with STX-478. The company’s presentation noted that five of those were unconfirmed responses at the data cutoff in June, but all have since become confirmed.
Adam Friedman“In the history of targeted oncology, the harder you hit the target for longer, usually that translates to better outcomes for patients,” Scorpion CEO Adam Friedman told Endpoints News ahead of the presentation. “We think we’re starting to see that in the monotherapy data. Of course, it’s quite early.”
He also noted that investors in the Series C did get to see early clinical trial results.
Breaking down the data by cancer type, five of 22 HR+/HER2- breast cancer patients responded to therapy. Nearly all of the breast cancer patients in the study had received a CDK inhibitor before.
Four of nine patients with gynecologic cancers also responded. Outside of breast cancer, Friedman noted, no PI3Kα-targeted drugs are approved.
Meanwhile, eight patients saw increased liver enzyme levels, five of which were grade 3 and one was grade 4. Scorpion noted in its presentation that the cases were “asymptomatic, transient and reversible,” and that one each of the grade 3 and 4 events was at a 160 mg dose, which was higher than the maximum tolerated dose of 100 mg moving forward.
There were no grade 3 or higher cases of toxicities that occurred from hitting wild-type PI3Kα, such as hyperglycemia, diarrhea and rash. In addition, no patients discontinued the study due to an adverse event.
One generation after another
Scorpion is competing with several companies in making a next-generation PI3Kα inhibitor. Discussant Alexander Drilon of Memorial Sloan Kettering Cancer Center separated PI3Kα inhibitors into several categories in which the treatments became increasingly more selective: Novartis’ Piqray and Roche’s inavolisib are “PI3Kα selective,” while Scorpion’s STX-478 and Relay Therapeutics’ experimental therapies are “PI3Kα mutant-selective” and spare the wild-type protein. The most selective is Lilly’s LOXO-783, which targets a specific PI3Kα mutant called H1047R.
Drilon noted that the mutant-selective PI3Kα inhibitors could “widen therapeutic windows.”
Piqray was approved for certain breast cancer patients in 2019, but comes with substantial side effects like high blood sugar and rash. In its pivotal trial in combination with fulvestrant, a quarter of patients discontinued the study due to adverse events.
Roche is awaiting a potential November approval in first-line patients with its PI3Kα inhibitor inavolisib in combination with other breast cancer treatments. And Relay shared data from a combo study earlier in September and said it plans to start a pivotal trial next year.
Friedman highlighted that Scorpion’s study enrolled pre-diabetic and diabetic patients, for whom there are typically restrictions in studies of PI3K inhibitors because of their known side effects, describing the study as having “what we believe is the most metabolically relaxed inclusion criteria for pathway inhibitors.”
“We really wanted to test whether our selectivity translated into this real world population that was already at risk for some of these toxicities. In particular, hypoglycemia can be quite extreme in these pre-diabetic and diabetic patients,” he said.
Moving forward, Scorpion is studying STX-478 in combination with CDK4/6 inhibitors and fulvestrant in first- and second-line HR+/HER2- breast cancer with PIK3CA mutations.
It’s also evaluating its options in other cancer types, where the mutation is known to play a role but there are no approved PI3Kα inhibitors approved yet, and Friedman said the company plans to “disclose more about those plans soon.”