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Oleclumab Plus Osimertinib Show Early Activity and Tolerability EGFR-Mutant NSCLC

*May 2021*

Note: Is further evaluation of the combination warranted for patients with locally advanced or metastatic T790M-negative, EGFR-positive NSCLC?

The combination of oleclumab (MEDI9447) and osimertinib (Tagrisso) was well-tolerated and demonstrated preliminary anti-tumor activity in patients with non-small-cell lung cancer (NSCLC) with an epidermal growth factor receptor mutation (EFGR) mutation after progression on an EGFR tyrosine kinase inhibitor (TKI), according to results from a phase 1B/2 study presented in a poster during the American Association for Cancer Research Annual Meeting 2021.

CD73 is often overexpressed in EGFR-mutant NSCLC and is a potential therapeutic target. The overexpression of CD73 is an independent indicator of poor prognosis. Inhabitation of CD73 may both inhibit tumor growth in vivo and increase sensitivity to EGFR TKIs in NSCLC tumor cells. Oleclumab is meant to bind to CD73. Osimertinib is a third-generation EGFR TKI inhibitor.

The non-randomized phase 1b/2 study (NCT03381274) enrolled 43 patients. Primary outcomes included incidence of adverse events (AEs) as a measure of safety and objective response rate as a measure of anti-tumor activity in the dose-expansion phase. Secondary outcomes included duration of response (DOR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), objective response by T790M status, disease control by TM90M status, serum oleclumab levels, serum osimertinib concentration levels, serum oleclumab concentration levels, and the development of detectable anti-drug antibody to oleclumab.

The study had 2 arms. In experimental arm A, patients received oleclumab and osimertinib. In experimental arm B, patients received oleclumab and AZD4635.

In order to participate, Patients must be 18 years old or older, weigh 35 kg or more, have an EGOG performance status of 0 or 1, and are diagnosed with histologically or cytologically confirmed locally advanced/metastatic NSCLC with EGFR mutation. Patients who were the recipients and EGFR TKI within 14 days of the first dose of the study treatment, the recipient of any conventional or investigation anticancer therapy not otherwise specified within 21 days of the planned first dose, prior receipt of any investigation immunotherapy, or concurrent enrollment in another therapeutic clinical study are not eligible to participate.

As of November 9, 2020, 5 patients were receiving 1500 mg IV of oleclumab every 2 weeks (Q2W) and 80 mg of osimertinib once daily (QD). Additionally, 21 patients were treatment with the investigational combination at the recommended phase 2 doses (RP2D) 3000 mg IV of oleclumab Q2W and 80 mg of osimertinib QD. This group included 6 patients who were in the dose-escalation phase and 15 in the dose-expansion phase, respectively.

Treatment with oleclumab and osimertinib achieved an ORR of 40% in the 5 patients who received DL1. Responses included partial responses (PRs) and stable disease (SD) in 40% of patients each. Twenty percent of patients in the cohort were not evaluable for response. The DOR observed with the combination was not assessable (NA; range, 4.8-18.1). The DCR in this cohort was 80%.

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