Table 3.
Selected triplet combinations targeting ER, CDK4/6, and PI3K/AKT/mTOR.
| TRINITI-1 | IPATUNITY 150 | NCT03006172 | NCT02684032 | |||
|---|---|---|---|---|---|---|
| N | 104 | 20 | 36 for arms E and F | 103; 59 for arms C and D | ||
| Phase | I/II | Ib/III | I/Ib | Ib (dose expansion) | ||
| Cohort details | HR+/HER2- ABC after progression on CDK4/6i | HR+/HER2- ABC after progression on first-line ET or primary endocrine-resistant | Primary endocrine-resistant, PIK3CA-mutated, HR+/HER2− ABC | Previously treated HR+/HER2−ABC; CDK4/6i-pretreated for arms C and D | ||
| Treatment arm | Exemestane + ribociclib + everolimus | Fulvestrant + palbociclib + ipatasertib | Fulvestrant + palbociclib + inavolisib | Fulvestrant + palbociclib + inavolisib + metformin (obese/prediabetic) | Fulvestrant + palbociclib + gedatolisib (weekly)(arm C) | Fulvestrant + palbociclib + gedatolisib (3weeks on, 1 week off)(arm D) |
| ORR (%) (95% CI) | 8.4 (3.7–15.9) | 55 (32–77) | 40 | 13 | 32 (16–52) | 63 (42–81) |
| CBR (%) (95% CI) | 41.1 (31.1–51.6) | 95 | 58% | 79 (59–92) | 96 (81–100) | |
| Median PFS (months) (95% CI) | 5.7 (3.6–9.1) | Not mature | Not reported | 5.1 (3.4–7.5) | 12.9 (7.4–16.7) | |
| AEs, % (All/≥ grade 3) | ||||||
| Neutropenia | 69.2/51.0 | 75/65 | 85/65 | 56/56 | 66/56 | 81/67 |
| Stomatitis | 40.4/2.9 | 40/0 | 80/10 | 50/0 | 88/22 | 89/22 |
| Diarrhea | 27.9/1.9 | 80/15 | 45/5 | 50/0 | 31/6 | 52/7 |
| Hyperglycemia | 18.3/6.7 | ~20/0 | 60/15 | 69/44 | 25/9 | 26/7 |
| Reference | Bardia et al.77 | Oliveira et al.159 | Bedard et al.160 | Layman et al.161 | ||
AI aromatase inhibitor, CDK4/6i cyclin-dependent kinase 4/6 inhibitor, CBR clinical benefit rate, DCR disease control rate, ET endocrine therapy, ORR objective response rate, PFS progression-free survival.