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Ref Type Abstract
PMID
Authors Y-K. Shi Y. Zheng J. Chen X. Yu J. Fang Y. Liu D. Huang T. Liu H. Shen S. Luo H. Yu Y. Cao X. Zhang
Title 1378P Efficacy and safety of tunlametinib (HL-085) combined with vemurafenib in patients with advanced BRAF V600-mutated solid tumors: A multicenter, phase I study
Journal Vol Issue Date Pages Journal Short Title
Annals of Oncology 34 Supplement 2 October 2023 S790
URL https://www.annalsofoncology.org/article/S0923-7534(23)03248-9/fulltext
Abstract Text Background: Addition of a MEK inhibitor to a BRAF inhibitor enhances tumour growth inhibition, delays acquired resistance of the MAPK pathway in BRAF V600-mutated cancers. We assessed the safety and efficacy of tunlametinib (HL-085), a novel highly selective MEK1/2 inhibitor, in combination with vemurafenib in patients(pts) with advanced BRAF-mutated solid tumors. Methods: In this phase I study, pts with advanced solid tumors who had progressed on or shown intolerance to standard treatment were enrolled and received escalating doses of tunlametinib combined with vemurafenib in dose-escalation phase (followed a 3 + 3 design). Patients received tunlametinib at dose levels of 0.5, 6, 9, 12, and 15 mg BID, together with vemurafenib 960 mg BID, in 21-day cycles. In dose-expansion phase, tunlametinib 12mg + vemurafenib 960mg, tunlametinib 12mg + vemurafenib 720mg and tunlametinib 9mg + vemurafenib 720mg dose groups were evaluated. The tunlametinib 9mg + vemurafenib 720mg was determined as the recommended phase 2 dose (RP2D). Results: As of the data cut-off date on 04, Nov, 2022, a total of 72 pts with solid tumors were enrolled. The most common AE were CK elevation, anemia and rash which were predominantly grade 1/2. 33 pts with non-small cell lung cancer (NSCLC) have been evaluated for response. The objective response rate (ORR) was 60.6% (95%CI: 42.1%, 77.1%), a median duration of response (DoR) was 11.3 months (95% CI: 3.9, NE), and a median progression free survival (PFS) was 11.7 months (95% CI: 5.6, NE) . At the RP2D, ORR was 60.0% (95%CI: 32.3%, 83.7%) and mPFS was 10.4 months (95% CI: 5.6, NE). 24 pts with metastatic colorectal cancer (mCRC) at all doses, ORR was 25.0% (95%CI: 9.8%, 46.7%), mDoR was 5.5 months (95% CI: 2.9, NE), and mPFS was 6.2 months (95% CI: 4.8, 7.6). Antitumor activity was also seen in papillary thyroid carcinoma and pancreatic ductal adenocarcinoma. Conclusions: Tunlametinib in combination with vemurafenib showed promising antitumor activity and manageable safety profile in pts with BRAF V600-mutated solid tumors. Further studies are ongoing. Clinical trial identification: NCT03781219.

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
BRAF V600X lung non-small cell carcinoma predicted - sensitive Tunlametinib + Vemurafenib Phase I Actionable In a Phase I trial, the combination of Tunlametinib (HL-085) and Zelboraf (vemurafenib) demonstrated safety and resulted in an objective response rate of 60.6% (20/33), a median duration of response of 11.3 months, and a median progression free survival of 11.7 months in patients with advanced non-small cell lung cancer harboring a BRAF V600 mutation (Ann Oncol (2023) 34 (suppl_2): S790; NCT03781219). detail...
BRAF V600X colorectal cancer predicted - sensitive Tunlametinib + Vemurafenib Phase I Actionable In a Phase I trial, the combination of Tunlametinib (HL-085) and Zelboraf (vemurafenib) demonstrated safety and resulted in an objective response rate of 25.0% (6/24), a median duration of response of 5.5 months, and a median progression free survival of 6.2 months in patients with advanced colorectal cancer harboring a BRAF V600 mutation (Ann Oncol (2023) 34 (suppl_2): S790; NCT03781219). detail...