Abstract C077: Updated results of phase 1 study of ripretinib (DCC-2618), a broad-spectrum KIT and PDGFRA inhibitor, in patients with gastrointestinal stromal tumor (GIST) by line of therapy (NCT02571036)
Bibliographic record
Abstract
Abstract Objective: Ripretinib (DCC-2618) is a kinase switch control inhibitor designed to broadly inhibit KIT and PDGFRA mutations. Based on clinical activity observed in heavily pretreated patients (pts) with GIST in a Phase 1 study (NCT02571036), ripretinib is under evaluation in two Phase 3 studies: INVICTUS (NCT03353753) in ≥4th-line pts and INTRIGUE (NCT03673501) in 2nd-line pts, each at the recommended dose of 150 mg once daily (QD). This abstract reports updated results from the escalation and expansion phases of the Phase 1 study for pts treated with ≥100 mg daily dose. Methods: The Phase 1 study includes a dose-escalation phase that tested oral ripretinib QD or twice daily (BID) in 28-day cycles, followed by an expansion phase with the recommended Phase 2 dose (RP2D) of 150 mg QD in 6 cohorts, including cohorts for pts with GIST based on prior regimens (2nd/ 3rd, 4th, and >4th-line). Local Response Evaluation Criteria in Solid Tumors (RECIST) response assessments were performed every 2 cycles and pts who progressed per RECIST in the expansion cohorts were allowed to dose escalate to 150 mg BID. Results: At a cut-off date of March 01, 2019, 179 pts with GIST in the escalation and expansion phases (median follow-up of 10.4 months; range, 0.1–32.3) were enrolled at dose levels of ≥100 mg daily with KIT-driven (169 pts), PDGFRA-driven (9 pts), or wild-type-driven GIST (1 pt). Of 178 pts with GIST treated at the ≥100 mg daily dose (1 pt was not included in the intent-to-treat population as the pt only participated in the food effect portion of the study), there were 37 2nd-line pts, 31 3rd-line pts, 60 4th-line pts, and 50 >4th-line pts. The objective response rate (ORR) by best response was 30% in 2nd-line pts (n=11; includes 3 unconfirmed responses), 23% in 3rd-line pts (n=7; includes 3 unconfirmed responses), and 11% in ≥4th-line pts (n=12; includes 4 unconfirmed responses); responses ≥4th-line include 15% in 4th-line pts (n=9; includes 4 unconfirmed responses) and 6% in >4th-line pts (n=3; includes no unconfirmed responses). In 2nd-line pts, the disease control rate (DCR) was 31% (n=9) at 52 weeks. The median progression-free survival (mPFS) was 42 weeks in 2nd-line pts, 40 weeks in 3rd-line pts, and 24 weeks in ≥4th-line pts (includes 30 weeks in 4th-line pts and 16 weeks in >4th-line pts). In 2nd-line pts, the median duration of response was 80 weeks and the median duration of treatment was 44 weeks. For any line, 13% of pts (n=24) experienced treatment-emergent adverse events (TEAEs) leading to study treatment discontinuation, 17% of pts (n=31) experienced TEAEs leading to dose reduction and 49% (n=88) had TEAEs leading to study drug interruption. Grade 3 or 4 TEAEs in >5% of pts were lipase increased (18%; n=33), anemia (11%; n=20), hypertension (7%; n=13), and abdominal pain (6%; n=11). Conclusion: In this Phase 1 study, ripretinib demonstrated encouraging clinical benefit (as measured by mPFS, ORR [best response] and DCR) and was generally well-tolerated in pts with GIST treated in the 2nd-line or later. Preliminary data from this Phase 1 study further supports testing in the ongoing Phase 3 study in 2nd-line GIST. Citation Format: Ping Chi, Filip Janku, Michael Heinrich, Kristen Ganjoo, Hans Gelderblom, Michael Gordon, Robin Jones, Albiruni Razak, Jonathan Trent, Margaret von Mehren, Simin Hu, Ying Su, Rodrigo Ruiz-Soto, Suzanne George. Updated results of phase 1 study of ripretinib (DCC-2618), a broad-spectrum KIT and PDGFRA inhibitor, in patients with gastrointestinal stromal tumor (GIST) by line of therapy (NCT02571036) [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics; 2019 Oct 26-30; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2019;18(12 Suppl):Abstract nr C077. doi:10.1158/1535-7163.TARG-19-C077
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".