Table 1.
Results from early phase SERD trials
| Trial | SERD and Doses Assessed | Phase | RP2D for Monotherapy | N (Total) | N (at RP2D) | % ESR1mut | % Prior CDK4/6i | % Prior Fulvestrant | Lines of Prior ET Median (Range) | DLTs | Adverse Events in ≥10% Patients (Any Grade) | Adverse Events Grade ≥3 | ORR at RP2D | CBR at RP2D | Median PFS |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| AMEERA-1(Parts A/B)86 | Amcenestrant 20-600mg | I/II | 400mg | 65 | 49 | 43% (21/49) | 61% (30/49) | 45% (22/49) | 2 (1-4) | Nil | Hot flush (10%) | Nil | 11% (5/46)– 1 CR, 4 PR | 28% (13/46) | NR |
| SERENA-1(Parts A/B)50 | Camizestrant 25-450mg | I | NR | 98 | NR | 43% (42/98)a | 62% (61/98)a | 53% (52/98)a | 2 (0-6)a | 3 DLTsb | Fatigue (11%), nausea (6%), bradycardia (4%), visual disturbance (3%)c | Dizziness (1%), bradycardia (1%), atrial fibrillation (1%), visual disturbance (1%), and as per DLTs | 10% (7/70)– all PRa | 35% (24/68)a | 5.4 months all doses |
| RAD1901–00549 | Elacestrant 200-600mg | I | 400mg | 57 | 50 | 50% (25/50) | 52% (26/50) | 52% (26/50) | 2.5 (1-7) | Nil | Nausea (33%), hypertriglyceridemia (25%), hypophosphatemia (25%) dyspepsia (21%), fatigue (21%), constipation (20%) | Hyperglycemia (4%) hypophosphatemia (8%) | 19% (6/31)– all PR | 43% (20/47) | 4.5 months 400mg |
| GO3993251 | Giredestrant 10-250mg | I | 30mg | 111 | 41 | 51% (21/41) | 66% (27/41) | 20% (8/41) | 1 (0-2)d | Nil | Nausea (20%), arthralgia (20%), back pain (17%), fatigue (17%), diarrhea (12%), constipation (12%) | NR | 15% (6/40)– all PR | 55% (22/40) | 7.2 months 30mg |
| EMBER90 | Imlunestrant 200-1200mg | I | 400mg | 114 | 51 | 49% (53/108)e | 92% (105/114)e | 51% (58/114)e | 2 (0-8)d | Nil | Nausea (35%), fatigue (28%), diarrhea (25%), arthralgia (15%), cough (13%), headache (10%), urinary infection (10%), hot flush (10%)f | Nausea (3%), fatigue (3%), diarrhea (1%) | 12% (4/34)– all PR | 55% (28/51) | 4.3 months all doses |
| G1T48-0184 | Rintodestrant 200-1000mg | I | 800mg | 67 | 7 | 45% (29/64)g | 86% (6/7) | 86% (6/7) | 4 (2-5)d | Nil | Hot flush (43%), fatigue (29%), diarrhea (14%) | Nil | 0% (0/7) | 14% (1/7) | 2.6 months 600mg, 3.6 months 1000mg |
| ZN-c5-00191 | ZN-c5 50–300mg | I | 50mg | 56 | 16 | 64% (9/14) | 44% (7/16) | 19% (3/16) | 1 (0-3) | Nil | Nil ≥10% | Nil | 0% (0/14) | 44% (7/16) | 3.9 months all doses |
Notes: Unless otherwise annotated, all percentages are relating to RP2D cohort only. aData only available for pooled population of 98 patients receiving doses 25–450 mg camizestrant. bDLTs observed were G3 QTc prolongation at 300 mg, G3 vomiting at 450 mg, G2 visual disturbance, headache and imbalance at 450 mg. cData on 98 patients enrolled only reports adverse events grade ≥ 2. dData only available for prior lines of therapy inclusive of chemotherapy. eData only available for the pooled population receiving imlunestrant across all dose levels. fData only available for pooled advanced breast cancer and endometrioid carcinoma patients receiving 400 mg imlunestrant. gData only available for the pooled population of 64 evaluable patients receiving rintodestrant across all dose levels.
Abbreviations: CBR, clinical benefit rate; CR, complete response; DLT, dose limiting toxicity; ET, endocrine therapy; N, patient enrolment; NR, not reported; ORR, objective response rate; PFS, progression free survival; PR, partial response; RP2D, recommended phase 2 dose; SERD, selective estrogen receptor degrader.