A phase Ib study to evaluate the oral selective estrogen receptor degrader GDC-9545 alone or combined with palbociclib in metastatic ER-positive HER2-negative breast cancer.

Abstract No : 1023

Abstract Type : Poster Discussion Session

Indication : Her2-Negative Breast Cancer

Intervention : GDC-9545 +/- palbociclib

Company : Genentech

Technology : Small Molecule


Eight-five pts were enrolled in 2 cohorts: GDC-9545 100 mg given once daily 6 LHRH agonist (Cohort A), and GDC-9545 100 mg +125 mg palbociclib on a 21 day on/7 day off schedule 6 LHRH agonist (Cohort B). Of the 39 pts in Cohort A, adverse events (AE) occurring in $10% of pts were fatigue, cough, back pain, pain in extremity, and arthralgia. Related AEs were generally Grade (G) 1-2; there were 3 related G3 AEs of fatigue, transaminase increased, and diarrhea. Two pts had GDC-9545 reduced, one due to G3 diarrhea and another due to G3 transaminitis. Of the 46 pts in Cohort B, AEs in $10% of pts were neutropenia, fatigue, bradycardia, diarrhea, constipation, dizziness, nausea, anemia, asthenia, thrombocytopenia, pruritus, and visual impairment. Twenty-six (57%) pts had G$3 AEs. G$3 neutropenia was reported in 23 (50%) pts. One pt had palbociclib reduced due to G3 febrile neutropenia. Eleven (13%) of 85 pts had G1 asymptomatic bradycardia considered related to GDC-9545. No pts in either cohort discontinued study treatment due to AEs. PK analysis and clinical data demonstrate no clinically relevant drug-drug interactions between GDC-9545 and palbociclib. Reduced ER, PR, and Ki67 levels, and an ER activity signature, were observed in paired pre- and on-treatment biopsies (n = 12). Eighteen of 33 pts in Cohort A had either confirmed partial responses or were on study 24 weeks (clinical benefit rate 55%). Clinical benefit was observed in pts with prior fulvestrant treatment and with detectable ESR1 mutations at enrollment. Clinical benefit data for both cohorts are anticipated to be mature in April 2020


GDC-9545 was well tolerated as a single agent and in combination with palbociclib with encouraging PK, PD, and antitumor activity in ER+ MBC to support Phase III development.


GDC-9545 is well tolerated as monotherapy and in combination with palbociclib, Further reserach required to explore its hidden potential for HR+ HER-breast cancer patients.

Refer to Her2-Negative Breast Cancer Market report for detailed Insights.