OGCT-06 EFFICACY OF IMMUNOTHERAPY REGIMENS WITHOUT BLOOD-BRAIN BARRIER OPENING (BBBO) IN PATIENTS WITH BRAIN METASTASES (BM) FROM NON-SMALL CELL LUNG CANCER (NSCLC)

Abstract Focused ultrasound (FUS) has emerged as a promising approach for BBBO and enhanced drug delivery of large-sized molecules like pembrolizumab, which has modest activity in patients with brain metastases (BM) from NSCLC. The BT020K and BT012 clinical trials evaluated the efficacy (at the metastasis level) and safety of pembrolizumab with/without chemotherapy and targeted BBBO using FUS or not for treating BM in patients with NSCLC. BT020K is an open-label, single-center study and BT012 is an ongoing, multicenter study with a non-randomized, safety run in phase. Overall, 12 patients were enrolled. In BT012, seven patients received pembrolizumab monotherapy without BBBO (n=17 metastases). In BT020K, five patients received pembrolizumab plus chemotherapy without BBBO (n=27 metastases). The use of gamma knife for BM without BBBO was allowed in BTO20K. High-resolution axial magnetic resonance images (MRIs) with T1-weighting and gadolinium enhancement were acquired before and after the first 6 pembrolizumab cycles, with three follow-up MRIs every 3 weeks. Metastasis volumes were estimated using the longest and perpendicular diameters; objective response rates (ORRs) were calculated based on changes from baseline in metastasis volumes. After pembrolizumab monotherapy without BBBO, metastasis volumes increased by an average of 10–31% across cycles 1–6, 10% at first follow-up and 6% at second follow-up and then decreased by 20% at final follow-up. Corresponding ORRs were 0–24% across cycles 1–6, 24% at the first two follow-ups and 53% at the final follow-up. After pembrolizumab plus chemotherapy without BBBO, metastasis volumes decreased by an average of 7–68% across cycles 1–6. Corresponding ORRs were 33–85% across cycles 1–6. These results support efforts to enhance BM response in patients treated with large-size molecules, supporting the rationale for enrolment into BBBO strategies as is being studied in BT012 and BT020K.