Abstract CT163: CD73 inhibitor oleclumab plus osimertinib for advanced EGFRm NSCLC: First report of a Phase 1b/2 study

Background: Patients (pts) with EGFRm T790M-negative NSCLC with progressive disease (PD) on an EGFR TKI have limited therapy options. CD73 may promote immune evasion and is overexpressed in EGFRm NSCLC, suggesting the potential for combining CD73 blockers with EGFR TKIs. Oleclumab (MEDI9447) disrupts immune evasion by binding to CD73. This phase 1b/2, multicenter, dose escalation/expansion study (NCT03381274) evaluates the safety and efficacy of oleclumab plus osimertinib (osi) in locally advanced/metastatic EGFRm NSCLC. Methods: Pts had histologically or cytologically confirmed T790M-negative EGFRm NSCLC by local testing, a TKI-sensitive EGFR mutation (exon 19 del, L858R), ECOG PS 0-1, PD on a 1st or 2nd generation TKI, and no prior osi. Oleclumab 1500 mg (DL1) or 3000 mg (recommended Phase 2 dose, RP2D) IV Q2W + osi 80 mg PO QD were given until PD or intolerable AEs. Primary endpoints included AEs, SAEs and ORR by RECIST v1.1. DLTs were predefined and reviewed by a dose-escalation committee. Secondary endpoints included duration of response, disease control rate, PFS and OS. Results: As of November 9, 2020, 5 pts received DL1 and 21 pts received RP2D. Minimum follow-up was 44 wks. For the 5 pts receiving DL1, safety profile and response rate were generally similar to RP2D and no DLTs occurred. All of the 21 pts receiving RP2D had ≥1 treatment-emergent AE (TEAE), 38.1% had Grade 3/4 TEAEs and 23.8% had SAEs. Treatment-related AEs (TRAEs) occurred in 81.0% (19.0% Grade 3/4); none were SAEs or deaths. The most common TRAEs were rash (33.3%), stomatitis (28.6%), diarrhea (23.8%) and paronychia (23.8%). At data cutoff, 38.1% remained on treatment; 47.6% discontinued due to PD, with death, pt decision and AE (pneumonitis) as other causes. Response and survival for pts receiving RP2D are shown in Table 1. Conclusions: Oleclumab + osi was well tolerated at RP2D. Compared to T790M-negative EGFRm NSCLC pts in a prior study of osi monotherapy, ORR was similar (21% vs 19%) but mPFS was longer (2.8 vs 11.0 mos). Table 1.Disease response and survivalOutcomeN=21Best overall response, n (%)CR0PR4 (19.0)SD13 (61.9)PD3 (14.3)Not evaluable1 (4.8)ORR, n (%)4 (19)Median duration of response, months (range)Not assessable (9.2-11.1)Disease control rate, n (%)17 (81.0)Median PFS (95% CI), months11 (3.7-not evaluable)6-month PFS rate (95% CI), %63.5 (38.3, 80.7)9-month PFS rate (95% CI), %52.9 (29.0, 72.1)Median OS (95% CI), monthsNot reached (11.7-not evaluable)6-month OS rate