4816 - Initial Results of Phase 1 Study of DCC-2618, a Broad-spectrum KIT and PDGFRa Inhibitor, in Patients (pts) with Gastrointestinal Stromal Tumor (GIST) by Number of Prior Regimens.

Background

DCC-2618, a kinase switch control inhibitor, broadly inhibits mutations in KIT exons 9, 11, 13, 14, 17 and 18. Based on clinical activity observed in heavily pretreated GIST pts in a Phase 1 study, DCC-2618 is being evaluated in a Phase 3 study, INVICTUS (NCT03353753), in ≥ 4^th line pts. Given the breadth of inhibition of KIT mutations and favorable tolerability profile, the Phase 1 study included expansion cohorts to assess clinical benefit in 2^nd and 3^rd line GIST pts in advance of the expected initiation of a second Phase 3 study in 2^nd line GIST pts by the end of 2018.

Methods

The Phase 1 study includes a dose-escalation component testing oral DCC-2618 dosed QD or BID in 28 day cycles and an expansion phase using the RP2D of 150 mg QDin 6 cohorts, including cohorts for GIST pts based on prior regimens (2^nd/3^rd, 4^th/>4^th). RECIST response assements based on local assessment of CT scans were performed every 2 cycles.

Results

At the cut off of April 18, 150 GIST pts were enrolled at dose levels of ≥ 100 mg/d with KIT (141 pts) or PDGFRa- (8 pts) -driven GIST. One pt had SDH-deficient GIST. 114 GIST pts were treated at the 150 mg QD dose, including 19, 27, and 68 pts who previously received 1, 2 or ≥ 3 prior lines of therapy, respectively. For the 114 GIST pts, ORR was 14%, 3-month DCR was 70%, mPFS was 24 weeks with 56% of the pts censored. For the 46 evaluable pts in 2^nd/3^rd line, ORR was 22%, 3-month DCR was 81% and mPFS was 36 weeks with 61% of the pts censored. Updated ORR, DCR and mPFS will be presented. Grade 3/4 adverse effects (regardless of attribution, in > 1 pt) for all 114 pts treated at 150 mg QD included asymptomatic lipase increase 11, anemia 4, hypertension 3, blood bilirubin increased 3, diarrhea 2, abdominal pain 2, back pain 2, hypophosphatemia 2, hyponatremia 2, hyperkalemia 2.

Conclusions

DCC-2618 demonstrated encouraging clinical benefit and a favorable tolerability profile in GIST pts treated in the 2^nd line or later. Clinical benefit as measured by ORR, DCR and mPFS was greater in 2^nd/3^rd line pts compared to more heavily pretreated pts. Preliminary data from the Phase 1 expansion supports further testing in the planned Phase 3 study in 2^nd line GIST.

Clinical trial identification

NCT02571036.

Legal entity responsible for the study

Deciphera Pharmaceuticals, Inc.

Funding

Deciphera Pharmaceuticals, Inc.

Editorial Acknowledgement

Disclosure

S. George, M. Heinrich, P. Chi, M. von Mehren, M. Gordon, N. Somaiah, F. Janku: Research sponsored: Deciphera Pharmaceuticals, Inc.; Scientific advisory board: Deciphera Pharmaceuticals, Inc. A. Razak, K.N. Ganjoo, J. Wolf, J. Rodon Ahnert: Research sponsored: Deciphera Pharmaceuticals, Inc. J.C. Trent: Scientific advisory board: Deciphera Pharmaceuticals, Inc. R. Ruiz-Soto, O. Rosen: Employee: Deciphera Pharmaceuticals, Inc.