NEW YORK – In the first readout from a study testing Amgen's Lumakras (sotorasib) plus chemotherapy in the first-line setting, the combination showed activity in patients with treatment-naïve KRAS-mutant advanced non-small cell lung cancer, prompting the drugmaker to begin a larger trial.
At the International Association for the Study of Lung Cancer World Conference on Lung Cancer on Sunday, researchers presented results from subprotocol F within the Phase Ib CodeBreaK 101 trial, which included NSCLC patients who received both first-line and second-line treatment with Lumakras plus carboplatin and pemetrexed.
Based on the promising results from CodeBreaK 101, Amgen on Sunday announced it will initiate the Phase III CodeBreaK 202 trial to compare Lumakras-carboplatin-pemetrexed against standard chemo plus Merck's checkpoint inhibitor Keytruda (pembrolizumab) in a first-line setting in a larger cohort of patients with KRAS G12C-mutant, PD-L1-negative advanced NSCLC. Amgen said it will begin enrolling the CodeBreaK 202 trial before year-end.
Among 20 evaluable patients who received the combination treatment in the first-line setting in CodeBreaK 101, 65 percent responded, and the disease control rate, including responders and those with stable disease, was 100 percent. In the second-line setting, 54 percent of 13 patients responded, and the disease control rate was 85 percent. The researchers found that patients responded to the treatment regimen regardless of their PD-L1 expression score, supporting Amgen's decision to study the combination in PD-L1-negative patients in the larger study.
At a median follow-up of three months, progression-free and overall survival data were immature. However, researchers observed durable responses in patients, said Jeffrey Clarke, an associate professor of medicine at Duke Cancer Institute, in presenting the results at the meeting.
"Additional follow-up is needed to assess the durability of response as well as the survival endpoints," Clarke said, noting that "this study adds to a growing body of data suggesting high response rates and promising clinical activity of the combination."
He highlighted that a prior investigator-led Phase II study by the West Japan Oncology Group also demonstrated efficacy of Lumakras plus chemo in the first-line KRAS-mutant NSCLC setting. In presenting data from that study in June at the American Society of Clinical Oncology's annual meeting, researchers reported a response rate of 88.9 percent, along with a six-month progression-free survival rate of 61.2 percent and six-month overall survival rate of 87 percent.
Nearly all patients in the CodeBreaK 101 trial experienced treatment-related adverse events. Twelve percent of patients who received first-line Lumakras-chemo and 31 percent of those who received it in the second-line discontinued treatment due to adverse events. The adverse events were consistent with what investigators have previously seen with Lumakras and platinum-based chemo regimens, Clarke said.
Lumakras is currently approved as a single agent in the US for previously treated, locally advanced, or metastatic NSCLC patients whose tumors harbor a KRAS G12C mutation. However, Amgen is testing Lumakras in combination with a range of other treatments in order to move it into earlier lines of treatment and improve its efficacy.
Within the CodeBreaK 101 trial, for example, there are cohorts of patients receiving Lumakras with Keytruda and other checkpoint inhibitors, with SHP2 inhibitors such as BridgeBio's BBP-398 and Revolution Medicines' RMC-4630, and with other targeted therapies.
"Combination treatment is an important approach to prevent or delay the onset of drug resistance and improve the depth and durability of targeted response in KRAS G12C-mutated NSCLC," Clarke said in a separate statement on the trial results presented at the conference.