181O Interim analysis (IA) of the atezolizumab (atezo) + sacituzumab govitecan (SG) arm in patients (pts) with triple-negative breast cancer (TNBC) in MORPHEUS-pan BC: A phase Ib/II study of multiple treatment (tx) combinations in pts with locally advanced/metastatic BC (LA/mBC)

Abstract

Cancer immunotherapy has transformed the TNBC tx landscape but new combinations are needed to further improve survival outcomes. Atezo (PD-L1 inhibitor) + nab-paclitaxel (nab-P) is approved for first-line (1L) tx of PD-L1+, inoperable LA/mTNBC. SG (Trop-2-directed antibody–drug conjugate) is approved for 2L+ tx of mTNBC. We present the 18-week IA of the atezo + SG arm in MORPHEUS-panBC (NCT03424005). Eligible pts with no prior systemic tx for PD-L1+, inoperable LA/mTNBC were randomised to receive control (atezo 840 mg IV on Day [D] 1 & 15 + nab-P 100 mg/m2 IV on D1, 8 & 15, of 28-D cycles) or atezo (1200 mg IV, D1) + SG (10 mg/kg IV, D1 & 8) of 21-D cycles, until unacceptable toxicity/loss of clinical benefit. Primary endpoints were objective response rate (ORR) and safety. Baseline tumours were evaluated for TROP-2 and PD-L1 IC expression for associations with response. At data cut-off (9 March 2023) 11 pts were enrolled in the control arm and 31 in the atezo + SG arm. More pts were aged <65 years in the atezo + SG arm (84%) vs. control (64%); liver and brain metastatic site distribution was similar between arms. ORR was 76.7% (n = 23; 5 complete responses) with atezo + SG vs. 66.7% (n = 6; all partial responses) with control; clinical benefit rate (CBR) was 83.3% vs. 66.7% (see table). Median (m) progression-free survival (PFS) data were immature but showed a trend towards benefit with atezo + SG vs. control (12.2 vs. 5.9 months [mo]; median follow-up: 10.6 vs. 11.7 mo). No new safety signals were seen; overall safety summary is shown in the table.Table: 181OPts*Atezo + nab-P (n = 9)Atezo + SG (n = 30)EfficacyResponders, n (%)(95% CI)6 (66.7)(29.9, 92.5)23 (76.7)(57.7, 90.1)DCR, n (%)(95% CI)9 (100)(66.4, 100)28 (93.3)(77.9, 99.2)CBR, n (%)(95% CI)6 (66.7)(29.9, 92.5)25 (83.3)(65.3, 94.4)mDoR, mo (95% CI)7.1 (2.8, NE)14.0 (8.7, NE)mPFS, mo (95% CI)5.9 (4.1, 8.7)12.2 (7.4, NE)PFS hazard ratio (95% CI)0.27 (0.11, 0.70)Safety, n (%)Pts with ≥1:AE9 (100)30 (100)Fatal AE00Grade 3–4 AE4 (44.4)21 (70.0)Serious AE4 (44.4)7 (23.3)Immune-related AE5 (55.6)24 (80.0)Tx-related AE (TRAE)9 (100)30 (100)TRAE leading to any tx withdrawal1 (11.1)1 (3.3)TRAE leading to dose modification/interruption3 (33.3)25 (83.3)* Efficacy- and safety-evaluable pts. Open table in a new tab * Efficacy- and safety-evaluable pts. Encouraging activity was seen with 1L atezo + SG tx in pts with PD-L1+ LA/mTNBC. PFS data were immature but showed a trend towards benefit with atezo + SG. Safety of atezo + SG was consistent with the profiles of the individual drugs, with no new safety signals seen.

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