Table 2.

Results from early phase trials of oral SERDs in combination with CDK4/6 inhibitors

Trial	SERD and CDK4/6 Inhibitor Combination	Phase	N	% ESR1 mut	%Prior CDK4/6i	% Prior Fulvestrant	Lines of Prior ET Median (Range)	Adverse Events in ≥10% Patients (Any Grade)	Adverse Events Grade ≥ 3	ORR	CBR	Median PFS
AMEERA-1 (Parts C/D)62,65	Amcenestrant 200mg + Palbociclib	I/II	39	NR	5% (2/39)	8% (3/39)	1 (0–4)	Neutropenia (95%), nausea (18%), fatigue (15%), arthralgia (10%), asthenia (10%), dry skin (10%), hot flushes (10%)	Neutropenia (56%), deep vein thrombosis (3%)	32% (11/34) – all PR	74% (25/34)	14.7 months
SERENA-1 (Parts C/D)53	Camizestrant 75mg + Palbociclib	I	25	44% (11/25)	80% (20/25)	68% (17/25)	2 (1–4)	Neutropenia (80%), visual disturbance (44%), bradycardia (16%), fatigue (16%), nausea (16%), vomiting (12%), diarrhea (12%)	Neutropenia (68%), infections (8%), anemia (4%)	12% (3/25) – 2 CR, 1 PR	28% (7/25)	NR
GO3993261,64	Giredestrant 100mg + Palbociclib +LHRH agonist	I	48	29% (14/48)	0% (0/48)	7% (3/48)	1 (0–2)	Neutropenia (77%), bradycardia (31%), diarrhea (33%), fatigue (29%), nausea (21%), constipation (21%), cough (21%), dizziness (19%), anemia (17%), thrombocytopenia (17%)	Neutropenia (60%), thrombocytopenia (6%), diarrhea (2%)	48% (21/44) – 5 CR, 16 PR	81% (39/48)	18.2 months
G1T48-0163	Rintodestrant 800mg + Palbociclib	I	40	41% (16/39)	0% (0/40)	15% (6/40)	1 (0–1)	Neutropenia (90%), leukopenia (45%), anemia (15%), asymptomatic bacteriuria (10%), thrombocytopenia (10%)	Neutropenia (53%), leukopenia (18%), anemia (5), lymphopenia (5%)	5% (2/40)– all PR	60% (24/40)	7.4 months

Abbreviations: CBR, clinical benefit rate; CR, complete response; DLT, dose-limiting toxicity; ET, endocrine therapy; LHRH, luteinizing hormone releasing hormone; N, patient enrollment; NR, not reported; ORR, objective response rate; PFS, progression-free survival; PR, partial response; SERD, selective estrogen receptor degrader.