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Merck & Co. Inc.’s experimental TIGIT drug, vibostolimab, failed to meet its primary endpoint in a Phase 2 trial for non-small cell lung cancer (NSCLC). The setback is the latest blow to the biopharmaceutical company’s efforts to develop a new class of cancer immunotherapies.
The trial involved patients with previously untreated advanced NSCLC treated with chemotherapy and Merck’s blockbuster cancer drug Keytruda. TIGIT, which works by blocking a protein that suppresses the immune system’s ability to attack tumors, was evaluated in combination with the two drugs.
However, according to Merck, the drug did not meet its primary endpoint of overall survival.
Merck & Co. announced on Thursday that an experimental drug it has developed in collaboration with Agenus, which combines its Keytruda with a TIGIT-blocking agent, failed to show a significant benefit in a Phase 2 trial for lung cancer. The drug, called MK-7684A, did not significantly delay tumor growth in patients with non-small cell lung cancer (NSCLC) who had previously undergone treatment with immunotherapy, which typically indicates a poor prognosis and high resistance to further treatment.
This setback is a blow to Merck, which has invested heavily in the TIGIT-blocking agent class of drugs as a way to bolster its immune-oncology portfolio and keep its flagship blockbuster Keytruda, which generated $21 billion in sales last year, competitive beyond the 2028 expiration of some of its essential patents.
Merck is not alone in the race to develop TIGIT-blocking agents. GSK and Bristol Myers Squibb are both advancing candidates, while Roche’s TIGIT drug failed in trials for small and non-small cell lung cancer, although the company continues to test it.
Merck has previously co-formulated Keytruda with another TIGIT-blocking agent called vibostolimab and tested it on its own in cancers such as melanoma. The combination was given to NSCLC patients who had progressed after treatment with Keytruda or similar immunotherapy paired with chemotherapy, according to a statement released by the company.
Unfortunately, the co-formulation in this study was not found to be significantly more effective than older chemotherapy called docetaxel. Stats also showed that the combination was less effective, especially when the numbers were through AI models.
TIGIT-blocking agents developed by Merck, Bristol Myers Squibb, and GSK are part of a new class of cancer drugs that seek to direct immune cells to kill cancerous cells in the body. TIGIT, a T-cell immunoreceptor with immunoglobulin and ITIM domain, is a protein found on immune cells that act as a brake on the immune system, reducing its ability to fight cancer cells. By blocking TIGIT, these drugs aim to unleash the immune system and enhance its ability to target and destroy cancerous cells.
While TIGIT-blocking agents have shown promise in preclinical studies, their efficacy in clinical trials has been mixed, leading to doubts over the approach.
Earlier this month, Roche reported disappointing results for its own TIGIT drug in a Phase 2 clinical trial for small cell lung cancer. At the same time, Gilead-partner Arcus Biosciences saw only modest benefits in a trial for NSCLC. However, other developers such as AstraZeneca and GSK have reported promising results for their own TIGIT-blocking agents in early-stage clinical trials for various types of cancer.
Despite the challenges, TIGIT-blocking agents remain a crucial milestone in the search for effective cancer treatments. Unlike other cancer therapies that target specific genetic mutations, TIGIT-blocking agents could potentially benefit a broader range of patients with different types of cancer.
Furthermore, as part of combination therapies, they could enhance the effectiveness of other immune checkpoint inhibitors such as Keytruda, which work by releasing the brakes on the immune system and allowing it to attack cancer cells.
The experiment will be a crucial assessment of medications that focus on TIGIT, similar to Keytruda, aiming to redirect immune cells to attack cancer cells. If successful, the combination of Keytruda and a TIGIT-targeting drug could serve as a strategic move for Merck to safeguard profits from its leading blockbuster drug, as some of its most substantial patents are set to expire in 2028.
However, the disappointing results from the trial have cast doubts on the use of TIGIT-blocking drugs in cancer treatment. The Food and Drug Administration (FDA) has not approved TIGIT-blocking drugs, and the mechanism has triggered debate among financial analysts and scientists.
The upcoming milestone for the strategy may be unveiled by Merck in the following month as they prepare to release the findings of their clinical trial involving MK-7684A and its effectiveness in treating melanoma at a prominent cancer research conference.
In the meantime, the disappointing results from the Phase 2 clinical trial of MK-7684A have cast doubt on the use of TIGIT-blocking drugs in cancer treatment.
However, some Wall Street analysts have taken the study’s “blinded” docetaxel arm as a sign that the chemo combination could eventually delay progression compared to chemo alone.
Merck’s TIGIT-blocking agent, MK-7684A, has failed to show a significant benefit in the Phase 2 clinical trial for NSCLC, adding to doubts over the approach and highlighting the challenges of developing effective cancer treatments.
The study’s failure to show any significant benefit to non-small cell lung cancer patients has cast doubt on the use of TIGIT-blocking drugs in cancer treatment, an approach that many pharmaceutical companies are exploring. While there is still much research to be done in this field, the results of this trial remind us that progress in cancer treatment is a slow and challenging process.