Submit Phase IV CT protocol for Entrectinib: CDSCO panel tells Roche India

This came after the firm presented its request for consideration of an alternative proposal to the Phase IV clinical trial of the anticancer drug Entrectinib 100 and 200 mg capsules.

Entrectinib is a tyrosine kinase inhibitor that acts on several receptors. It functions as an ATP competitor to inhibit tropomyosin receptor tyrosine kinases (TRK) TRKA, TRKB, TRKC, as well as proto-oncogene tyrosine-protein kinase ROS1 and anaplastic lymphoma kinase (ALK).

TRK receptors produce cell proliferation via downstream signaling through the mitogen activated protein kinase, phosphoinositide 3-kinase, and phospholipase C-γ.4 ALK produces similar signalling with the addition of downstream JAK/STAT activation. Inhibition of these pathways suppresses cancer cell proliferation and shifts the balance in favor of apoptosis resulting in shrinking of tumor volume.

Earlier, the Medical Dialogues Team had reported that drug major, Roche Products had got approval from the Subject Expert Committee (SEC) of the Central Drugs Standard Control Organization (CDSCO) to manufacture and market anti-cancer Entrectinib capsules of 100 mg and 200 mg for the treatment of metastatic non-small cell lung cancer.

This approval was subject to the condition that the firm conduct a Phase IV clinical trial in the country in 50 patients, for which the protocol should be submitted to CDSCO within two months of the drug's approval for review by the committee.

Regarding the above condition, at a recent SEC meeting, the firm presented its request for consideration of an alternative proposal to a Phase IV clinical trial.

The committee noted the following alternative proposals to the Phase IV CT study of the firm:

1. The participation of Indian centres in global clinical trials: two Phase III studies would include Indian patients for a total of 18 patients.

2. The voluntary conduct of a Pilot Study for tumors agonistic and rare conditions (TARC): a cohort of additional patients would be recruited from a large apex center which routinely uses NGS screening panel that includes the mutations of interest and from HCPs pan-India in an RWE basket study.

After a detailed assessment, the committee decided to stick with its original recommendation. Accordingly, the committee directed the firm to submit the Phase IV clinical trial protocol before the committee.