Table 3.
Ongoing clinical trials of next-generation endocrine therapies in the metastatic, adjuvant, and neoadjuvant setting.
| Endocrine agent | ET class | Combination therapy (drug class) | Disease setting | Trial description | Phase | Clinical trial identifier |
|---|---|---|---|---|---|---|
| First-line metastatic breast cancer trials | ||||||
| Oral SERDs | ||||||
| Amcenestrant (SAR439859) | SERD | Palbociclib (CDK4/6i) | Advanced/metastatic; first line | Amcenestrant + palbociclib versus letrozole + palbociclib for treatment-naïve ER + MBC | Phase III | NCT04478266 (AMEERA-5) |
| Camizestrant (AZD9833) | SERD | Palbociclib (CDK4/6i) | Advanced/metastatic; first line | Camizestrant + palbociclib versus AI + palbociclib for treatment-naïve ER + MBC | Phase II | NCT04711252 (SERENA-4) |
| Giredestrant (GDC-9545) | SERD | Palbociclib (CDK4/6i) | Advanced/metastatic; first line | Giredestrant + palbociclib versus letrozole + palbociclib for treatment-naïve ER + MBC | Phase III | NCT04546009 (persevERA) |
| Second-line plus metastatic breast cancer trials | ||||||
| Oral SERDs | ||||||
| Amcenestrant (SAR439859) | SERD | None | Advanced/metastatic | Amcenestrant versus AI or fulvestrant or tamoxifen for ER + MBC progressed on ET | Phase II | NCT04059484 (AMEERA-3) |
| Amcenestrant (SAR439859) | SERD | Various | Advanced/metastatic | Amcenestrant + palbociclib, alpelisib, everolimus, or abemaciclib for ER + MBC progressed on ET | Phase I–II | NCT03284957 (AMEERA-1) |
| Camizestrant (AZD9833) | SERD | None | Advanced/metastatic | Camizestrant versus fulvestrant for ER + MBC progressed on ET | Phase II | NCT04214288 (SERENA-2) |
| Camizestrant (AZD9833) | SERD | Various | Advanced/metastatic | Camizestrant alone or in combination with palbociclib, abemaciclib, everolimus, or capivasertib for ER + MBC progressed on ET | Phase I | NCT04214288 (SERENA-1) |
| Camizestrant (AZD9833) | SERD | Abemaciclib/palbociclib (CDK4/6i) | Advanced/metastatic | Camizestrant + palbociclib or abemaciclib versus AI + palbociclib or abemaciclib for ESR1 mutant ER + MBC before progression | Phase III | NCT04964934 (SERENA-6) |
| Giredestrant (GDC-9545) | SERD | None | Advanced/metastatic | Giredestrant versus fulvestrant or AI for ER + MBC progressed on ET | Phase II | NCT04576455 (acelERA) |
| Imlunestrant (LY3484356) | SERD | Various | Advanced/metastatic | Imlunestrant alone or combined with abemaciclib, everolimus, alpelisib, trastuzumab, or AI for ER + MBC | Phase I | NCT04188548 (EMBER) |
| Imlunestrant (LY3484356) | SERD | Abemaciclib (CDK4/6i) | Advanced/metastatic | Imlunestrant with or without abemaciclib versus fulvestrant or exemestane for ER + MBC progressed on ET | Phase III | NCT04975308 (EMBER-3) |
| Rintodestrant (G1T48) | SERD | Palbociclib (CDK4/6i) | Advanced/metastatic | Rintodestrant + palbociclib for ER + MBC progressed on ET | Phase I | NCT03455270 |
| Borestrant (ZB-716) | SERD | Palbociclib (CDK4/6i) | Advanced/metastatic | Borestrant alone or combined with palbociclib for ER + MBC | Phase I–II | NCT04669587 (ENZENO) |
| ZN-c5 | SERD | Abemaciclib (CDK4/6i) | Advanced/metastatic | ZN-c5 + abemaciclib for ER + MBC | Phase I | NCT04514159 |
| ZN-c5 | SERD | Palbociclib (CDK4/6i) | Advanced/metastatic | ZN-c5 alone or combined with palbociclib for ER + MBC | Phase I–II | NCT03560531 |
| D-0502 | SERD | Palbociclib (CDK4/6i) | Advanced/metastatic | D-0502 alone or combined with palbociclib for ER + MBC progressed on ET | Phase I | NCT03471663 |
| SERMs + SERM/SERD hybrids | ||||||
| Lasofoxifene | SERM | Abemaciclib (CDK4/6i) | Advanced/metastatic | Lasofoxifene + abemaciclib for ESR1 mutant ER + MBC progressed on ET | Phase II | NCT04432454 (ELAINE-2) |
| Lasofoxifene | SERM | None | Advanced/metastatic | Lasofoxifene versus fulvestrant for ESR1 mutant ER + MBC progressed on AI + CDK4/6i | Phase II | NCT03781063 (ELAINE) |
| Bazedoxifene | SERM/SERD hybrid | Palbociclib (CDK4/6i) | Advanced/metastatic | Bazedoxifene + palbociclib for ER + MBC progressed on prior ET | Phase II | NCT02448771 |
| Other novel ET | ||||||
| H3B-6545 | SERCA | Palbociclib (CDK4/6i) | Advanced/metastatic | H3B-6545 + palbociclib for ER + MBC progressed on ET | Phase I | NCT04288089 |
| H3B-6545 | SERCA | None | Advanced/metastatic | H3B-6545 for ER + MBC progressed on ET + CDK4/6i | Phase I–II | NCT03250676 |
| OP-1250 | CERAN | None | Advanced/metastatic | OP-1250 for ER + MBC progressed on ET | Phase I–II | NCT04505826 |
| OP-1250 | CERAN | Palbociclib (CDK4/6i) | Advanced/metastatic | OP-1250 + palbociclib for ER + MBC | Phase I | NCT05266105 |
| ARV-471 | PROTAC | Palbociclib (CDK4/6i) | Advanced/metastatic | ARV-471 alone or combined with palbociclib for ER + MBC progressed on ET | Phase I–II | NCT04072952 |
| AC682 | Chimeric ER degrader | None | Advanced/metastatic | AC682 for ER + MBC | Phase II | NCT05080842 |
| Adjuvant breast cancer trials | ||||||
| Oral SERDs | ||||||
| Amcenestrant (SAR439859) | SERD | None | Adjuvant | Amcenestrant versus tamoxifen for early ER + breast cancer after discontinuation of AI | Phase III | NCT0512877 (AMEERA-6) |
| Giredestrant (GDC-9545) | SERD | None | Adjuvant | Giredestrant versus AI or tamoxifen for early ER + breast cancer | Phase III | NCT04961996 (lidERA) |
| Neoadjuvant breast cancer trials | ||||||
| Oral SERDs | ||||||
| Elacestrant (RAD1901) | SERD | None | Neoadjuvant | Elacestrant for ER + early breast cancer prior to surgery | Phase I | NCT04797728 |
| Camizestrant (AZD9833) | SERD | None | Neoadjuvant | Camizestrant for ER + early breast cancer prior to surgery | Phase II | NCT04588298 (SERENA-3) |
| Imlunestrant (LY3484356) | SERD | None | Neoadjuvant | LY3484356 for ER + early breast cancer prior to surgery | Phase I | NCT04647487 (EMBER-2) |
| SERM/SERD hybrids | ||||||
| Bazedoxifene | SERM/SERD Hybrid | None | DCIS | Bazedoxifene + conjugated estrogens for DCIS | Phase II | NCT02694809 (PROMISE) |
AI, aromatase inhibitors; CERAN, complete estrogen receptor antagonist; CDK4/6i, CDK4/6 inhibitor; DCIS, ductal carcinoma in situ; ER+, estrogen receptor positive; ET, endocrine therapy; MBC, metastatic breast cancer; PROTAC, proteolysis targeting chimer; SERCA, selective estrogen receptor covalent antagonist; SERD, selective estrogen receptor degrader; SERM, selective estrogen receptor modulators.