An experimental oral treatment that targets a genetic mutation involved in the development of pancreatic cancer has shown promising results in patients with metastatic disease previously treated with chemotherapy. The first clinical data indicate a reduction of tumors in some patients and support the continuation of research in a phase III study.
Pancreatic cancer is one of the most aggressive forms of cancer, and therapeutic options remain limited, especially after disease progression under available treatments. The identification of therapies that act directly on the genetic changes responsible for the growth of tumors is an important direction of research.
The American biopharmaceutical company Verastem Oncology announced new results from the phase I/II TARGET-D 101 clinical trial, which evaluates the experimental drug VS-7375 in patients with advanced solid tumors who have the KRAS G12D mutation, according to News.ro.
KRAS is a gene involved in the control of cell growth and multiplication. The G12D mutation can cause the abnormal activation of the KRAS protein, favoring the development and progression of cancer.
VS-7375 is an orally administered drug designed to block the KRAS G12D protein in both its active and inactive states in order to interrupt the signals that support cancer cell growth.
The study, conducted in several medical centers in the United States, included more than 200 patients with various advanced tumors, including pancreatic, colorectal and lung cancer.
Response to treatment
In the metastatic pancreatic adenocarcinoma group, the main analysis presented by the company included 22 chemotherapy-experienced patients who received 900 mg of VS-7375 daily without the addition of other antitumor drugs.
According to the results communicated by the company, 41% of the patients (9 out of 22) registered an objective tumor response, confirmed by repeated imaging evaluations.
In the subgroup of eight patients who had previously received only one line of treatment, the confirmed response rate was 50%.
Two complete responses were also reported, characterized by the disappearance of tumor lesions detectable on imaging evaluation. In one of the cases, the disappearance of the lesions was confirmed by repeating the imaging investigations, and in the other, the confirmation was still pending.
At the level of the whole group, 86% of the patients presented either the reduction of the tumors or the maintenance of the disease without progression.
At six months, the estimated progression-free survival rate was 67%, and 16 of the 22 patients were continuing treatment at the time of analysis. The median follow-up period was 6.4 months.
Adverse reactions
The researchers also observed changes in some biological indicators associated with the disease. In 15 of the 17 patients with initially elevated values of the tumor marker CA 19-9, its level decreased by more than 50%.
In addition, in seven of the 12 patients evaluated for circulating tumor DNA, fragments of genetic material originating from tumors and detectable in blood became undetectable during the analyzed period.
In terms of safety, the most frequent adverse reactions associated with the treatment were nausea, vomiting and diarrhea, predominantly of mild or moderate intensity. In the larger group of patients who received the same dose, 2% discontinued treatment due to adverse reactions.
The results are preliminary and come from a phase I/II study without a chemotherapy-treated comparison group. The number of evaluated patients with pancreatic cancer is small, and the follow-up period is still short. The data were presented by the company and require confirmation in larger clinical studies.
Phase III study
The pharmaceutical company announced that it has reached an agreement with the US Food and Drug Administration (FDA) regarding the design of a phase III study in patients with metastatic pancreatic cancer who are about to start the first line of treatment.
The study will compare the administration of VS-7375 in combination with a drug that blocks the epidermal growth factor receptor (EGFR), the administration of VS-7375 in combination with chemotherapy and standard chemotherapy.
The drug remains experimental and is not authorized for clinical use in the European Union or the United States.
The results support the potential of selective inhibition of the KRAS G12D protein as a therapeutic strategy in metastatic pancreatic cancer.
The phase III trial will need to determine whether this approach can improve disease control and survival compared to available treatments.
