MAGELLAN arms B1 and B3: Durvalumab plus chemotherapy with and without oleclumab in treatment-naïve metastatic non-small-cell lung cancer.

[OBJECTIVES] Standard-of-care therapies for metastatic non-small-cell lung cancer (mNSCLC) have mixed outcomes that remain unsatisfactory. Durvalumab (anti-PD-L1) plus oleclumab (anti-CD73) might provide a synergistic antitumor effect by antagonizing separate immune pathways. We report safety, efficacy, pharmacokinetics, and immunogenicity findings of durvalumab + chemotherapy ± oleclumab as first-line treatment of mNSCLC from Arms B1 and B3 in the phase 1B MAGELLAN (NCT03819465) study.

[METHODS] In Cohort B, treatment-naïve adults with histologically/cytologically confirmed mNSCLC and PD-L1 expression on < 50 % tumor cells were eligible. Patients received investigator's choice of chemotherapy plus 1500 mg durvalumab three-weekly (Q3W) for four cycles and durvalumab Q4W thereafter in Arm B1, with addition of 2250 mg oleclumab Q3W for four cycles and 3000 mg Q4W thereafter in Arm B3. Primary endpoint was safety and tolerability; key secondary endpoint was efficacy by investigator-assessed objective response rate (ORR; RECIST v1.1).

[RESULTS] Patient demographics and disease characteristics were generally consistent between arms. All but one patient experienced treatment-emergent adverse events (AEs). Grade 3 or 4 AEs and AEs leading to discontinuation occurred in 14/33 (42.4 %) and 3/33 (9.1 %) patients in Arm B1 and 18/32 (56.3 %) and 6/32 (18.8 %) patients in Arm B3. No treatment-related deaths occurred in Arm B1; one (3.1 %) fatal AE of unknown cause was deemed possibly related to both durvalumab and oleclumab by the investigator in Arm B3. ORR was 36.4 % (95 % CI, 20.4-54.9) and 21.9 % (95 % CI, 9.3-40.0) in Arms B1 and B3, respectively - all partial responses. Median duration of response was 11.8 months (95 % CI, 3.2-26.6) and 8.8 months (95 % CI, 2.3-not calculable), respectively.

[CONCLUSION] No new safety signals were identified for durvalumab + chemotherapy ± oleclumab in patients with mNSCLC and PD-L1 expression < 50 %. The lack of meaningful efficacy improvements limits potential further development of this combination in this disease setting.