Express | KRAS mutation patients have a remission rate of 70%, and innovative RAF/MEK inhibitors are recognized as breakthrough therapy

▎Editor of WuXi AppTec Content Team On May 21, 2021, Verastam Oncology announced that its innovative small molecule RAF/MEK inhibitor VS-6766 has been granted a breakthrough therapy designation by the US FDA and combined with the specific FAK inhibitor defactinib to treat relapses Low-grade serous ovarian cancer (LGSOC).

The results of early clinical trials of this combination therapy showed that the objective response rate (ORR) for patients with KRAS mutant tumors was 70%, the ORR for KRAS wild-type tumors was 44%, and the objective response rate for all patients was 52%, and Safety and tolerance are good.

KRAS mutations are common in pancreatic cancer (90%), colorectal cancer (40%), non-small cell lung cancer (25%), and also in thyroid cancer, ovarian cancer, bladder cancer and other diseases.

Mutations in the RAS family drive 30% of human cancers.
Targeting the RAS-RAF-MEK-ERK tumor signaling pathway has always been a hot spot in the development of anti-cancer therapies.

However, in tumor cells, inhibiting the RAS signaling pathway may cause the cells to activate FAK-mediated signaling pathways, thereby producing resistance to RAS signaling pathway inhibitors.

Therefore, more comprehensive inhibition of the signal pathway that promotes the growth of cancer cells can achieve the effect of killing cancer cells.

VS-6766 is a small molecule dual inhibitor that can simultaneously inhibit the activities of RAF and MEK, while defactinib can specifically inhibit the activities of FAK and related protein kinase PYK2.

The combination of the two can more comprehensively inhibit the signaling pathways used by cancer cells to develop drug resistance.

▲VS-6766 can inhibit RAF and MEK at the same time (picture source: Verastem Oncology official website) This combination therapy is being evaluated in a phase 1/2 multi-center, randomized double-blind, parallel grouping, open-label FRAME clinical trial, which is included in the group 24 patients.

Early results showed that the total ORR was 52% (11/21), the ORR of patients with KRAS mutation was 70% (7/10), and the ORR of patients with KRAS wild-type was 44% (4/9).

The most common side effects are skin rash, elevated creatine kinase, nausea, hyperbilirubinemia and diarrhea.
All adverse reactions are reversible.

Many patients have been treated for more than one year, proving the potential of this therapy as a long-term treatment option.

Mr.
Brian Stuglik, Chief Executive Officer of Verastem, said, “This breakthrough therapy designation will help us prove that the combination of VS-6766 and defactinib produces strong and lasting relief and convincing safety in LGSOC patients.
A new treatment method may be brought to these patients as soon as possible.

Most LGSOC is driven by the RAS pathway, and we are committed to exploring the potential of VS-6766 as a backbone therapy for solid tumors driven by the RAS pathway.

"Reference: [1] Verastem Oncology Receives Breakthrough Therapy Designation for VS-6766 with Defactinib in Recurrent Low-Grade Serous Ovarian Cancer.
May 24, 2021, fromen/Verastem-Oncology-Receives-Breakthrough-Therapy-Designation-for-VS-6766-with-Defactinib-in-Recurrent-Low-Grade-Serous-Ovarian-Cancer[2] Verastem Oncology (VSTM) Gets FDA Breakthrough Therapy Designation For VS-6766.
May 24, 2021, from] Verastem wins breakthrough nod for combo therapy in ovarian cancer; EMA picks up speedy review of BioMarin's gene therapy.
May 24, 2021, from https://endpts.
com/verastem-wins-breakthrough-nod-for-combo-therapy-in-ovarian-cancer-ema-picks-up-speedy-review-of-biomarins-gene-therapy/Note: This article aims to introduce the progress of medical and health research , Is not a treatment plan recommendation.If you need guidance on the treatment plan, please go to a regular hospital for treatment.