ASCO-GI – Leap falters again
Randomised data will be needed to answer lingering questions about DKN-01.
Randomised data will be needed to answer lingering questions about DKN-01.
Leap Therapeutics, having already fallen last week on ASCO-GI abstract data, sank another 6% on Tuesday following more detailed results from the Defiance trial of its lead project, DKN-01.
The uncontrolled first part of the study tested DKN-01 plus Avastin and chemo in second-line colorectal cancer; the concern was that, with around half of patients naive to Avastin, responses might have been driven by the Roche drug.
The overall response rate in Avastin-naive patients was 43%, well above the 15% seen in Avastin-experienced subjects, supporting the bear case. However, PFS was longer in the Avastin-experienced group, albeit among small patient numbers.
When asked for a potential explanation for the discrepancy, Leap’s chief executive officer, Douglas Onsi, told ApexOnco that most of the Avastin-naive patients were either rapid progressers on their first line of therapy, or had a contraindication to Avastin, such as a bleeding tumour. Rapid progressers “would not be expected to do well on second-line therapy, even with the addition of Avastin”, he noted via email.
However, he added that factors other than prior Avastin might have been more important to outcomes, such as where the cancer originated in the colon. During a conference call on Tuesday, the company highlighted higher response rates in patients with cancer originating in the left side of the colon, versus the right side; and in those with rectal and rectosigmoid tumours.
Randomised data might help address some of the lingering concerns around DKN-01, and Leap’s shareholders now face a nervous wait for results from part B of Defiance, comparing DKN-01 plus Avastin and chemo versus an Avastin/chemo combo. Enrolment is expected to complete by mid-2024.
When asked if it might now focus on left-sided disease, the company said it was too late to change the enrolment criteria of part B, but added that it was expecting around 75% of patients to have this subtype, in line with part A.
Defiance part A: results by prior Avastin use
| ORR | mPFS | |
|---|---|---|
| Avastin-experienced | 15% (2/13) | 7.3 months (17 pts) |
| Avastin-naive | 43% (6/14) | 5.9 months (16 pts) |
| Total population | 30% (8/27) | 6.3 months (33 pts) |
*Note: the ORR in Avastin-naive patients was changed from 36% to 43% after ApexOnco alerted Leap Therapeutics to an error in the slide deck. This is an updated version of a previous quick take. Source: ASCO-GI & company presentation.
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