Breast Cancer development UPDATES
- P3 DESTINY-Breast06 (NCT04494425): Trastuzumab deruxtecan in 2L+ HR+/HER2-low/-ultralow mBC with prior ET progression but no prior chemo
- Company guidance continues to anticipate a readout in H1 2024 though data is not listed on the current ASCO 2024 program
- Management commented that they are “eagerly awaiting” the readout in order to bring T-DXd into an earlier LoT which directly competes with the ASCENT-07 patient population; The data may also broaden the ENHERTU eligible patient population to include the HER2-ultra low population
- PFS in the HER2-low population was stated to be the endpoint with analysis in the HER2-ultra population being “descriptive”
- P3 TROPION-Breast01 (NCT05104866): Datopotamab deruxtecan (Dato-DXd; TROP2 ADC) in 2L+ HR+/HER2- mBC with 1L or 2L prior chemo
- Regulatory submissions have been accepted in the US, EU, and China, with potential approval in 2025 (in line with the FDA’s PDUFA date of Jan 29, 2025)
- The BLA acceptance by the US FDA in Apr 2024 was highlighted to be one of the Q1 2024 milestones
- AZ stated filing in Japan has been submitted; DS’ FY 2023 earnings call indicated that the filing was accepted in Japan in March 2024 with a regulatory decision expected in in Q4 2024 – Q1 2025 (JP H2 FY2024)
- Dato-DXd remains a high competitive threat with the ability to enter the HR+/HER2- mBC setting in an earlier LoT, though data presented at ESMO 2023 did not significantly differentiate Dato-DXd from TROPiCS-02
- Regulatory submissions have been accepted in the US, EU, and China, with potential approval in 2025 (in line with the FDA’s PDUFA date of Jan 29, 2025)
- P3 TROPION-Breast02 (NCT05374512): Datopotamab deruxtecan in 1L TNBC not candidates for anti-PD-(L)1
- Company guidance continues to anticipate a readout in H2 2024 which will compete directly with the ASCENT-03 study
- P3 CAPItello-291 (NCT04305496): Capivasertib + fulvestrant in 2L HR+/HER2- mBC after AI
- AZ highlighted a strong initial US launch and the recent Japan approval of capivasertib, with multiple global markets under regulatory review
- Regulatory approval continued to be expected in H1 2024 in the EU and in 2025 in China
- Management noted an uptake in the biomarker (PIK3CA/AKT1/PTEN-altered) confined population with a testing rate > 60% in the US and believe that it will overtake the current SoC (PI3K inhibitor)
- AZ believe the AKT class will provide an opportunity for patients to continue to stay on ET-based therapies longer potentially delaying use of chemotherapy and/or ADCs
- AZ highlighted a strong initial US launch and the recent Japan approval of capivasertib, with multiple global markets under regulatory review
- P3 CAPItello-290 (NCT03997123): Capivasertib + paclitaxel in 1L mTNBC
- Company guidance continues to anticipate a readout in H1 2024; If capivasertib’s TNBC label is confined to a biomarker population despite having all-comers data, its threat to Trodelvy will be reduced
- P3 SERENA-6 (NCT04964934): Camizestrant + CDK4/6i in 1L ESR1m HR+/HER2- mBC
- Company guidance continues to anticipate a readout in 2025
- P1 SERENA-1 (NCT03616587): Camizestrant combinations in 2L+ HR+/HER2- mBC
- Company guidance continues to anticipate a readout in H2 2024
- Company guidance is anticipating data readouts from the following early phase trials in 2025:
- P1/2 CYCAD-1 (NCT06188520): AZD8421 (CDK2i) combinations in 2L+ ER+/HER2- mBC
- P2 BEGONIA (NCT03742102): Durvalumab (Imfinzi; anti-PD-L1) + trastuzumab deruztecan / datopotamab deruxtecan in 1L mTNBC
- Company guidance is anticipating data readouts from the following Phase 3 trials in >2025:
- P3 TROPION-Breast03 (NCT05629585): Datopotamab deruxtecan ± durvalumab in Stage I-III TNBC without pCR following neoadjuvant therapy
- P3 TROPION-Breast04 (NCT06112379): Neoadjuvant/adjuvant datopotamab deruxtecan + durvalumab in Stage I-III TNBC or HR-low/HER2- BC
- P3 TROPION-Breast05 (NCT06103864): Datopotamab deruxtecan ± durvalumab in 1L PD-L1+ TNBC
- P3 CAPItello-292 (NCT04862663):Capivasertib + palbociclib + fulvestrant in early relapse/endocrine-resistant HR+/HER2- mBC
- P3 SERENA-4 (NCT04711252): Camizestrant + palbociclib in 1L ER+/HER2- mBC
- P3 CAMBRIA-1 (NCT05774951): Adjuvant camizestrant in ER+/HER2- eBC after 2yrs of standard adjuvant ET
- P3 CAMBRIA-2 (NCT05952557): Adjuvant camizestrant ± abemaciclib in ER+/HER2- eBC with intermediate-high or high risk of recurrence that has completed definitive locoregional therapy
- P1/2 (NCT05123482): AZD8205 (B7-H4 ADC) in 2L+ mBC (previously 2025)
- Merck initiated recruitment of the Phase 3 MK-2870-010 trial evaluating MK-2870 (sacituzumab tirumotecan/SKB264; TROP2 ADC) ± pembrolizumab (Keytruda; anti-PD-1) vs treatment of physician’s choice (TPC) in chemo-naïve HR+/HER2- mBC
- The trial’s recruitment status was updated from “Not yet recruiting” to “Recruiting”
- SSD was updated from Mar 29, 2024 to Apr 13, 2024
- MK-2870-010 marks the first Merck-sponsored pivotal trial for MK-2870 in breast cancer and directly competes against ongoing ASCENT-07 trial
- Given MK-2870 is a late-to-market entry with multiple pivotal trials ongoing for ADCs in the chemo-naïve HR+ population, Merck may potentially be positioning its ADC-IO combination as an avenue for efficacy differentiation
- Roche terminated the Phase 1b/3 IPATunity150 trial evaluating ipatasertib (AKT inhibitor) + palbociclib (Ibrance, CDK4/6i) + fulvestrant vs placebo + palbociclib + fulvestrant in 1-2L HR+/HER2- mBC after prior adj or 1L ET
The decision to not proceed with the Phase 3 study was noted to be based on a strategic sponsor decision and not any safety concerns
Roche has previously removed ipatasertib from their development timeline following the failure of the Phase 3 IPATunity130 trial of ipatasertib + paclitaxel in PIK3CA/AKT1/PTENaltered TNBC and HR+/HER2- mBC
Novartis announced that it has paused new patient enrollment for ribociclib’s (Kisqali, CDK4/6i) eBC trials and will implement manufacturing adjustments to ensure alignment with the latest regulatory standards by Q2 2024
The guidance was published by the FDA in Aug 2023 on the recommended acceptable limit for the intake of nitrosamine impurities, which are potentially carcinogenic by-products produced unintentionally during manufacturing and storage process
By Aug 2025, all companies are expected to be in compliance with the guidelines
Patient use or commercial supply will not be impacted for ribociclib’s approved indication of 1-2L HR+/HER2- mBC
Though the company declined to comment on the number of trials affected, it expects no change in ribociclib’s regulatory timelines, including the potential approval based on the Phase 3 NATALEE trial guided for H2 2024
Novartis has filed for FDA approval of adjuvant ribociclib +ET in HR+/HER2- eBC based NATALEE in Q4 2023
Source: AstraZeneca (AZ) Q1 2024 earnings (Webcast, PR, Presentation, Clinical Trials Appendix)