Just a day ago Sunesis Pharmaceuticals (SNSS) has provided a clinical update on their progress with Vecabrutinib program. Unfortunately the company is said to discontinue and pivot from their advancement its non-covalent BTK inhibitor vecabrutinib into the planned Phase 2 portion of the Phase 1b/2 trial in adults with relapsed/refractory chronic lymphocytic leukemia (CLL) and other B-cell malignancies.
The decision was made after assessing the totality of the data including the 500 mg cohort, the highest dose studied in the trial.
Although vecabrutinib continues to exhibit an excellent safety profile, there is insufficient evidence of activity in BTK-inhibitor resistant B-cell malignancies to advance the drug into the planned Phase 2 portion of the trial. One partial remission was observed after 11 treatment cycles in a CLL patient treated in Cohort 5 (300 mg BID) and a number of patients treated across the dose range explored (25 mg to 500 mg BID) saw stable disease; however, no other remissions have been observed.
We will complete the Phase 1b and evaluate the best path forward for vecabrutinib. We are grateful for the patients and their families who participated in this trial, as well as the investigators and research staff at our trial sites.
Dayton Misfeldt, Interim Chief Executive Officer of Sunesis
Vecabrutinib Phase 1b/2 Clinical update. Currently, five patients enrolled in cohorts 5-7 remain on treatment and continue to be followed. Vecabrutinib is very well tolerated across the dose range investigated.
- Cohort 7 (500mg BID): Three (2 CLL, 1 MCL) of six treated patients had stable disease at first response assessment (beginning of cycle 4). One of the CLL patients is in Cycle 7, the MCL patient is in cycle 6 and one CLL patient was determined to have progressive disease after 6 cycles. We did not see a reduction in tumor burden in any of the patients with stable disease.
- Cohort 6 (400mg BID): Of 6 patients treated, 2 CLL patients remain on study in cycle 9, one with stable disease and the other who had progressive disease at first assessment but continues to derive clinical benefit. One CLL patient who had stable disease with a 48% reduction in tumor burden at first assessment progressed in cycle 7.
- Cohort 5 (300mg BID): One CLL patient remains on treatment in cycle 12 with a partial response observed at third response assessment done at the start of cycle 12.
Sunesis Pharmaceutical (SNSS) Vecabrutinib
The reason why sunesis is pulling the plug on the program is because it doesn’t work. They can not get above the 50% threshold required.
Sunesis Pharmaceutical (SNSS) shifts focus to SNS-510
Mr Misfeldt continued: “We are shifting our resources and development focus to our first-in-class PDK1 inhibitor SNS-510. SNS-510 inhibits PI3K-dependent and PIP3-independent pathways important in both solid and hematologic malignancies. We remain on track to file an IND by the end of 2020 and expect to present additional preclinical findings at a medical meeting in the second half of the year. We expect that our current cash resources are sufficient to fund the company into 2021.”
These programs were part of Sunesis’ 2004 multi-kinase inhibitor collaboration with Biogen (Nasdaq: BIIB).
In 2011, Japanese drug major Takeda’s (TYO: 4502) US subsidiary Millennium has entered a license agreement for the development of Sunesis’ oral, selective pan-Raf kinase inhibitor and one additional undisclosed kinase inhibitor program in oncology.
Evaluation of SNS-510 in the Eurofins Oncopanel, a panel of >300 genomically-profiled cancer cell lines from diverse tissue origins, indicated that CDKN2A-mutated tumors are particularly sensitive to SNS-510, noted Sunesis. CDKN2A alterations are common in human cancers and may prove to be useful biomarkers for broad investigation of SNS-510 as a monotherapy and in combination with other anticancer agents.
Sunesis, which has yet to bring a product to market, is conducting an Investigational New Drug (IND)-enabling program for SNS-510 and plan to file an IND by the end of 2020..
