Patients with non-small cell lung cancer (NSCLC) who had ceased to respond to EGFR TKI therapy demonstrated a rapid and robust response to the investigational agent BI-1482694 (HM61713).
BI-1482694 received a breakthrough therapy designation from the FDA in December, 2015 for the treatment of patients with NSCLC based on phase I/II data presented at the 2015 ESMO Asia Congress.2
In that study, the objective response rate (ORR) by independent assessment with BI-1482694 was 62% for patients withT790M-positive NSCLC. When looking specifically at those with a response confirmed on subsequent scans, the response rate with BI-1482694 was 46%. The overall disease control rate with BI-1482694 was 91% by independent review.
The results presented at ELCC are from an extension cohort where the disease control rate was 91% in 63 patients following treatment with the investigational agent. ORR by independent review was 62%; in 43 responding patients, 27 (84%) patients showed response by treatment cycle 2. Tumor response was confirmed in 32 (46%) patients. The median duration of response was not reached as of data cutoff.
The ORR was similar among patients whether they had received an EGFR TKI or chemotherapy as the last treatment before study entry.
“BI-1482694 is a novel, third-generation, oral EGFR TKI that specifically targets tumors harboringT790Mmutations, which are the most common mechanism of acquired resistance seen in about 50% of patients following first- and second-generation EGFR TKI treatent,” explained Jin-Soo Kim, MD, of Seoul National University.
The maximum tolerated dose of 800 mg/day, established in the phase I/II dose escalation studies, was used in the expansion cohort of patients that had previously received EGFR TKIs for advanced EGFR mutation-positive NSCLC. All patients were required to have a documented T790M mutation. The majority (76%) had been treated with gefitinib, followed by erlotinib and afatinib. Patients receiving additional lines of systemic therapy were also eligible
Of the 76 evaluable patients at data cutoff June 30, 2015, 44 were female, 61 had an ECOG performance status ≤1, and 57 had received 2 or more lines of systemic therapy. Treatment duration with BI-1482694 ranged from 1 to 39 weeks; 46 patients remained on the drug at data cutoff.
“At the recommended phase II dose of 800 mg, BI-1482694 showed meaningful clinical activity with a favorable safety profile in T790M-positive patients progressing on initial EGFR TKI treatment,” Kim reported.
“Preliminary signs of activity in metastatic brain disease were observed in a 62-year-old man who achieved a complete response in the target brain lesion by cycle 6,” Kim continued. “The patient continues on treatment and maintains the complete response.”
The most common treatment-related adverse events included diarrhea, reported by 55% of patients, rash (38%), nausea (37%), and pruritis (36%). Grade 3 rash and pruritis were reported by 5% and 1% of patients, respectively.
Drug-related adverse events (DRAEs) occurred in 73 patients, and serious DRAEs were reported in 9 patients. DRAEs led to treatment discontinuation in 3 patients. No cases of QT prolongation syndrome or hyperglycemia were reported. The authors announced that ELUXA 1, a global phase II trial (NCT02485652) further evaluating the efficacy and safety of BI-1482694 in T790M-positive NSCLC, is ongoing and recruiting participants. “The broader ELUXA clinical trial program is in development to assess Bl-1482694 in different settings of EGFR-mutation positive NSCLC,” Kim said.