Benzinga | Aug 17, 2020 04:34PM EDT

Deciphera Announces The Publication Of QINLOCK Phase 1 Study Results In Patients With Gastrointestinal Stromal Tumor In Journal O Clinical Oncology

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Results Consistent with Those Presented at the 2019 AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics and Support Ongoing INTRIGUE Phase 3 Clinical Study in Patients with Second-line GIST -

Deciphera Pharmaceuticals, Inc. (NASDAQ:DCPH), today announced that the Journal of Clinical Oncology has published results from its Phase 1 study of QINLOCK, the Company's switch-control tyrosine kinase inhibitor, in patients with second-line through fourth-line plus gastrointestinal stromal tumor (GIST). The article, entitled "Switch control inhibition of KIT and PDGFRA in patients with advanced gastrointestinal stromal tumor (GIST): a phase 1 study of ripretinib," is now available online and will be published in a future print issue of Journal of Clinical Oncology.

"QINLOCK continues to demonstrate encouraging clinical benefit in earlier lines of treatment following imatinib therapy," said Matthew L. Sherman, MD, Executive Vice President and Chief Medical Officer of Deciphera. "We believe that these positive results strongly support the ongoing INTRIGUE pivotal Phase 3 study, which is our registration-enabling study in patients with second-line GIST. We are committed to unlocking the full potential of QINLOCK to benefit patients and look forward to completion of enrollment in the INTRIGUE study, expected later this year."

The publication highlighted results from the Company's ongoing Phase 1 study of ripretinib in patients with second-line through fourth-line plus GIST. These published results are from 142 GIST patients receiving 150 mg of ripretinib once daily (QD) as the starting dose, which is the dose utilized in both of the Company's registration-enabling trials, INVICTUS and the ongoing INTRIGUE study, as of an August 31, 2019 data cutoff date. Results were consistent with those previously presented at the 2019 AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics.

The table below includes local, investigator-assessed objective response rate (ORR) by best response as determined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, median duration of response, and median progression free survival (mPFS).

2nd Line 3rd Line ?4th Line Line of Therapy (n=31) (n=28) (n=83)

ORR (confirmed responses only) 19.4% 14.3% 7.2%

Median Duration of Response 18.4 months NE(1) 17.5 months

mPFS 10.7 months 8.3 months 5.5 months

(1) NE = not estimable.

Ripretinib was generally well tolerated with adverse events consistent with previously presented Phase 1 data in patients with GIST. Grade 3 or 4 treatment-emergent adverse events (TEAEs) in >5% of patients were increase in lipase level (n=25; 18%), anemia (n=10; 7%), hypertension (n=8; 6%) and abdominal pain (n=13; 9%).

About QINLOCK (ripretinib)

QINLOCK is a switch-control tyrosine kinase inhibitor that was engineered to broadly inhibit KIT and PDGFR? mutated kinases by using a unique dual mechanism of action that regulates the kinase switch pocket and activation loop. QINLOCK inhibits primary and secondary KIT mutations in exons 9, 11, 13, 14, 17, and 18 involved in GIST, as well as the primary exon 17 D816V mutation involved in systemic mastocytosis, or SM. QINLOCK also inhibits primary PDGFR? mutations in exons 12, 14, and 18, including the exon 18 D842V mutation, involved in a subset of GIST.

QINLOCK is approved by the U.S. FDA for the treatment of adult patients with advanced GIST who have received prior treatment with 3 or more kinase inhibitors, including imatinib. It is also approved by Health Canada for the treatment of adult patients with advanced GIST who have received prior treatment with imatinib, sunitinib, and regorafenib and by the Australian Therapeutic Goods Administration for the treatment of adult patients with advanced GIST who have received prior treatment with 3 or more kinase inhibitors, including imatinib.

Deciphera Pharmaceuticals is developing QINLOCK for the treatment of KIT and/or PDGFR?-driven cancers, including GIST, SM, and other cancers. Deciphera Pharmaceuticals has an exclusive license agreement with Zai Lab (Shanghai) Co., Ltd. for the development and commercialization of QINLOCK in Greater China (Mainland China, Hong Kong, Macau, and Taiwan). Deciphera Pharmaceuticals retains development and commercial rights for QINLOCK in the rest of the world.

U.S. Indication and Important Safety Information About QINLOCK

Indications and Usage

QINLOCK (ripretinib) is a kinase inhibitor indicated for the treatment of adult patients with advanced gastrointestinal stromal tumor (GIST) who have received prior treatment with 3 or more kinase inhibitors, including imatinib. For more information visit QINLOCK.com.

Important Safety Information

There are no contraindications for QINLOCK.

Palmar-plantar erythrodysesthesia syndrome (PPES): In INVICTUS, Grade 1-2 PPES occurred in 21% of the 85 patients who received QINLOCK. PPES led to dose discontinuation in 1.2% of patients, dose interruption in 2.4% of patients, and dose reduction in 1.2% of patients. Based on severity, withhold QINLOCK and then resume at same or reduced dose.

New Primary Cutaneous Malignancies: In INVICTUS, cutaneous squamous cell carcinoma (cuSCC) occurred in 4.7% of the 85 patients who received QINLOCK with a median time to event of 4.6 months (range 3.8 to 6 months). In the pooled safety population, cuSCC and keratoacanthoma occurred in 7% and 1.9% of 351 patients, respectively. In INVICTUS, melanoma occurred in 2.4% of the 85 patients who received QINLOCK. In the pooled safety population, melanoma occurred in 0.9% of 351 patients. Perform dermatologic evaluations when initiating QINLOCK and routinely during treatment. Manage suspicious skin lesions with excision and dermatopathologic evaluation. Continue QINLOCK at the same dose.

Hypertension: In INVICTUS, Grade 1-3 hypertension occurred in 14% of the 85 patients who received QINLOCK, including Grade 3 hypertension in 7% of patients. Do not initiate QINLOCK in patients with uncontrolled hypertension. Monitor blood pressure as clinically indicated. Based on severity, withhold QINLOCK and then resume at same or reduced dose or permanently discontinue.

Cardiac Dysfunction: In INVICTUS, cardiac failure occurred in 1.2% of the 85 patients who received QINLOCK. In the pooled safety population, cardiac dysfunction (including cardiac failure, acute left ventricular failure, diastolic dysfunction, and ventricular hypertrophy) occurred in 1.7% of 351 patients, including Grade 3 adverse reactions in 1.1% of patients.

In INVICTUS, Grade 3 decreased ejection fraction occurred in 2.6% of the 77 patients who received QINLOCK and who had a baseline and at least one post-baseline echocardiogram. Grade 3 decreased ejection fraction occurred in 3.4% of the 263 patients in the pooled safety population who received QINLOCK and who had a baseline and at least one post-baseline echocardiogram.

In INVICTUS, cardiac dysfunction led to dose discontinuation in 1.2% of the 85 patients who received QINLOCK. The safety of QINLOCK has not been assessed in patients with a baseline ejection fraction below 50%. Assess ejection fraction by echocardiogram or MUGA scan prior to initiating QINLOCK and during treatment, as clinically indicated. Permanently discontinue QINLOCK for Grade 3 or 4 left ventricular systolic dysfunction.

Risk of Impaired Wound Healing: QINLOCK has the potential to adversely affect wound healing. Withhold QINLOCK for at least 1 week prior to elective surgery. Do not administer for at least 2 weeks following major surgery and until adequate wound healing. The safety of resumption of QINLOCK after resolution of wound healing complications has not been established.

Embryo-Fetal Toxicity: QINLOCK can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential and males with female partners of reproductive potential to use effective contraception during treatment and for at least 1 week after the final dose. Because of the potential for serious adverse reactions in the breastfed child, advise women not to breastfeed during treatment and for at least 1 week after the final dose. QINLOCK may impair fertility in males of reproductive potential.

Adverse Reactions: The most common adverse reactions (?20%) were alopecia, fatigue, nausea, abdominal pain, constipation, myalgia, diarrhea, decreased appetite, PPES, and vomiting. The most common Grade 3 or 4 laboratory abnormalities (?4%) were increased lipase and decreased phosphate.

The safety and effectiveness of QINLOCK in pediatric patients have not been established.

Administer strong CYP3A inhibitors with caution. Monitor patients who are administered strong CYP3A inhibitors more frequently for adverse reactions. Avoid concomitant use with strong CYP3A inducers.

Please click here to see the full U.S. Prescribing Information for QINLOCK.