Drugs to Watch: Lung Cancer

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The FDA is currently reviewing tarlatamab for small-cell lung cancer with a review date in June and datopotamab deruxtecan for non-small cell lung cancer with a review date in the fourth quarter.

Two new lung cancer therapies are being reviewed by the FDA. One is Amgen’s tarlatamab, which, if approved, would be the first bispecific antibody to treat a solid tumor. Amgen is seeking an indication for adult patients with advanced small cell lung cancer after disease progression on platinum-based chemotherapy. The FDA has set a Prescription Drug User Fee Act date of June 12, 2024.

Small cell lung cancer is an aggressive solid tumor with a median survival of about 12 months following initial therapy and a 7% five-year relative survival rate.

Tarlatamab is a first-in-class bispecific T-cell engager that targets CD3 on T cells and delta-like ligand 3 (DLL3) on small cell lung cancer cells. About 85% to 96% of patients have expression of DLL3 on the surface of small cell lung cancer cells, with minimal expression in normal cells. If approved, it would be the first for approved bispecific antibody to treat a solid tumor.

The application is based on the phase 2 trial results, which demonstrated antitumor activity with a durable response and encouraging survival outcomes in patients with previously treated small cell lung cancer. An objective response occurred in 40% of the patients in the 10-mg group and in 32% of those in the 100-mg group. Among patients with an objective response, the duration of response was at least six months in 59%. The estimates of overall survival at nine months were 68% of patients in the 10-mg group and 66% of patients in the 100-mg group.

Amgen is conducting additional trials of tarlatamab in small cell lung cancer: a phase 1b study evaluating tarlatamab in combination with an anti-PD-1 therapy in second-line treatment; a phase 1b study investigating tarlatamab in combination with standard of care therapies in first-line treatment; and a phase 3 trial comparing tarlatamab monotherapy with standard of care chemotherapy in second-line treatment; and the recently-initiated phase 3 trial of tarlatamab following chemoradiotherapy in earlier settings.

Amgen is also investigating tarlatamab in a phase 1b study of tarlatamab in de novo or treatment-emergent neuroendocrine prostate cancer.

Regulators are also reviewing datopotamab deruxtecan (Dato-DXd) to treat adult patients with locally advanced or metastatic nonsquamous non-small cell lung cancer (NSCLC) who have received prior systemic therapy. If approved, Dato-DXd would be the first TROP2-directed antibody-drug conjugate to treat patients with non-small cell lung cancer. The FDA’s action date is in the fourth quarter of 2024. This year, there will be about 234,580 new cases of lung cancer and about 125,070 deaths from lung cancer, according to the American Cancer Society. Non-small cell lung cancer is the most common type of lung cancer.

Dato-DXd is being jointly developed by AstraZeneca and Daiichi Sankyo. TROP2 is a protein that is expressed in the majority of NSCLC tumors.

The application is based on results from a phase 3 trial in which Dato-DXd reduced the risk of disease progression or death by 25% in the overall population and by 37% in patients with nonsquamous tumor. For overall survival, interim results favored Dato-DXd over docetaxel in the overall population; however, results did not reach statistical significance at the time of data cutoff. The trial is ongoing and overall survival will be assessed at final analysis.

An BLA application for datopotamab deruxtecan to treat adult patients with metastatic hormone receptor-positive, HER2-negative breast cancer has been accepted by the FDA. In the phase 3 program in patients with breast cancer, datopotamab deruxtecan reduced the risk of disease progression or death by 37%, providing a two-month median progression-free survival benefit, and was well tolerated in post-endocrine therapy setting.

Datopotamab deruxtecan is also being studied in combination with the AstraZeneca drug Imfinzi (durvalumab) as a first-line therapy to treat patients with metastatic triple-negative breast cancer. Two phase 3 trial are ongoing.

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