Lumakras-Novel Drug Combination to Be Studied in KRAS-Mutant Lung Cancer, Solid Tumors

A clinical trial recently kicked off to study the effects of combining the novel drug BBP-398 plus Lumakras in patients with lung cancer that harbors a KRAS G12 mutation.

The first patient was treated in a phase 1/2 clinical trial evaluating the novel drug BBP-398 plus Lumakras (sotorasib) in patients with non-small cell lung cancer (NSCLC) that harbors a KRAS G12C mutation, according to BridgeBio Pharma, the manufacturer of BBP-398.

“The survival rate following a diagnosis of NSCLC with a KRAS mutation is extremely poor. We are hopeful that by launching this clinical trial with Amgen (the manufacturer of Lumakras), we may be able to fill the current gap in unmet medical need for these (patients with cancer),” said Frank McCormick, chairman of oncology at BridgeBio, in a press release, noting that the Food and Drug Administration granted the trial a Fast Track designation.

Of note, a Fast Track designation is given to speed up the development and review of therapies that can treat unmet medical needs.

The phase 1 portion of the study will include patients with KRAS-mutant NSCLC that has not previously been treated with a KRAS G12 inhibitor and is aimed at determining the optimal dose of BBP-398.

Then, the phase 2 portion will evaluate the safety, tolerability, efficacy and how BBP-398 moves through and works within the body when combined with Lumakras. This later phase of the trial will be open to patients with any type of solid tumor that harbors a KRAS G12 mutation.

“People with metastatic NSCLC with a KRAS mutation often do not respond well to standard chemotherapy and immunotherapy options,” Dr. Rohit Joshi, director for Cancer Research SA (CRSA) and an associate professor at the University of Adelaide in Australia, said in the release. “They might have a worse prognosis than patients without a KRAS mutation and it is essential to deliver better therapeutic options to people with this difficult-to-treat cancer.”

BBP-398 works by inhibiting SHP2, a protein that promotes the growth of cancer cells. Researchers are hoping that combining the drug with the KRAS G12-inhibitor, Lumakras, will prevent oncogenesis (the process by which healthy cells turn cancerous) and overactive cancer cell proliferation, according to the press release.

"To date, preclinical data for SHP2 inhibition has shown promise in unlocking possible combination strategies to treat patients suffering from a range of cancers, including NSCLC,” said Dr. Benjamin G. Neel, co-founder of Navire Pharma Inc. (a subsidiary of BridgeBio) and director of the Perlmutter Cancer Center at NYU Langone in New York City.


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