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Deciphera details stomach cancer flop against Pfizer’s Sutent, cracking the door open for off-label use

Deciphera Pharmaceuticals recently took a serious hit to its billion-dollar hopeful cancer drug Qinlock. As the company undertakes a round of layoffs to deal with the blow, newly unveiled data offer a glimmer of hope for additional uptake—though likely not for an official FDA approval.

Qinlock, already approved for fourth-line gastrointestinal stromal tumor, failed to prove its use last year as a second-line treatment after Novartis’ Gleevec when compared with Pfizer’s Sutent. But now, new results show that the drug offers some encouraging efficacy in certain patient subgroups and—perhaps more importantly—a clear safety edge, according to results presented at an American Society of Clinical Oncology plenary session.

While an FDA greenlight seems out of reach, Deciphera might get Qinlock’s second-line use onto treatment guidelines and therefore receive some off-label use, Piper Sandler analyst Christopher Raymond said in a Monday note.

As Deciphera unveiled in November 2021, Qinlock showed a numerical 12% improvement in preventing disease progression or death over Sutent in previously treated GIST patients with a KIT exon 11 primary mutation in the phase 3 Intrigue study. Patients on Qinlock lived a median 8.3 months without progression, versus 7 months for Sutent. The KIT exon 11 subtype comprises about 70% of GIST cases.

Additional data revealed at the ASCO meeting showed Qinlock shrunk tumors in more patients with the KIT exon 11 subtype than Sutent, with response rates of 23.9% and 14.6% for the two meds.

And in a finding that gets Deciphera, an ASCO expert and Raymond optimistic, Qinlock showed a more favorable safety profile than Sutent, as fewer Qinlock patients experienced grade 3 to 4 side effects. For all enrolled patients, which included other disease subtypes, those side effects occurred in 41.3% Qinlock patients compared with 65.6% in the Sutent group. When it comes to side effects deemed as drug-related, the rates were 26.5% for Qinlock and 55.2% for Sutent.

Qinlock also saw fewer dose reductions, interruptions or treatment discontinuations because of side effects.

“It is important to recognize that the side-effect profile of [Qinlock] is more favorable with lower rates of hypertension, hand-foot skin reaction and neutropenia. This is an important factor in considering treating options for patients,” said Muhammad Shaalan Beg, M.D., an ASCO expert in gastrointestinal cancer from UT Southwestern Medical Center, in a statement.

With these data, Deciphera intends to submit Qinlock’s second-line GIST use for inclusion in the National Comprehensive Cancer Network’s (NCCN) guidelines, Raymond noted, citing a company exec. An NCCN inclusion could help with securing reimbursement and drive some off-label use for Qinlock in the absence of a formal FDA nod, Raymond said.

Before the Intrigue trial flop, industry watchers had high hopes for Qinlock’s second-line opportunity. SVB Leerink analyst Andrew Berens had figured the earlier-line indication could mean $1.37 billion in peak sales for the med. The indication was so important for Deciphera that the trial flop wiped over 70% off the company’s stock price, which hasn’t recovered at all.

Now, the drug’s potential in the second-line setting will depend on off-label adoption, which Deciphera can’t actively promote. But even with a potential NCCN backing, Raymond said he wouldn’t project “the opening of the 2L floodgates just yet” for Qinlock. The reason? Sutent has gone generic, which will pose a pricing challenge to Qinlock.