Core Insights - BridgeBio Oncology Therapeutics, Inc. (BBOT) announced positive preliminary safety and antitumor data for its three small molecule RAS and PI3Kα programs, including BBO-8520, BBO-11818, and BBO-10203 [1][2] BBO-8520 Findings - BBO-8520 demonstrated a 65% objective response rate (ORR) and a 66% six-month progression-free survival (PFS) in patients with KRAS mutant non-small cell lung cancer (NSCLC) [3][9] - The safety profile of BBO-8520 was generally well-tolerated, with no dose-limiting toxicities (DLTs) and no grade ≥4 treatment-related adverse events (TRAEs) reported [9][15] - In combination with pembrolizumab, BBO-8520 showed promising efficacy, with all patients experiencing tumor reduction regardless of PD-L1 status [9][15] BBO-11818 Findings - BBO-11818 showed early anti-tumor activity, including a confirmed partial response in a patient with pancreatic ductal adenocarcinoma (PDAC) and a 56% tumor reduction [9][10] - The monotherapy treatment appeared generally tolerable with no DLTs and primarily gastrointestinal-related TRAEs [9][10] - Ongoing studies are evaluating BBO-11818 in heavily pretreated patients with KRAS mutant solid tumors [6][9] BBO-10203 Findings - BBO-10203 demonstrated a differentiated safety profile with no observed hyperglycemia and no DLTs [15] - The recommended go-forward dose for BBO-10203 is 500 mg, with combination studies initiated in colorectal cancer and breast cancer [10][15] - Clinical benefits were observed in heavily treated patients with colorectal cancer and hormone receptor-positive breast cancer [15] Upcoming Catalysts - BBOT plans to provide additional data updates for BBO-8520, BBO-11818, and BBO-10203 in the second half of 2026 [12][15] - Combination studies with BBO-10203 and other product candidates are expected to open later in 2026 [15]

Core Insights - The Phase 3 HERIZON-GEA-01 trial results indicate that Ziihera (zanidatamab-hrii) in combination with chemotherapy, with or without tislelizumab, is positioned to become the new standard of care for HER2-positive first-line metastatic gastroesophageal adenocarcinoma (GEA) [1][2][4] Efficacy Summary - The trial achieved a median overall survival (OS) of 26.4 months for Ziihera plus tislelizumab and chemotherapy, which is the longest reported in a Phase 3 trial for this indication, showing a greater than seven-month improvement compared to the control arm [2][4][5] - Median progression-free survival (PFS) was over one year, with a 35% reduction in the risk of disease progression or death compared to trastuzumab plus chemotherapy, representing a more than four-month improvement [4][5] - The objective response rate (ORR) was 70.7% for Ziihera plus tislelizumab and chemotherapy, compared to 65.7% for the control arm [5] Safety Profile - The safety profile of Ziihera in combination with chemotherapy was consistent with known effects of HER2-directed therapy, with no new safety signals identified [6][7] - Grade 3 treatment-related adverse events (TRAEs) were reported at 71.8% for Ziihera plus tislelizumab and chemotherapy, and 59.0% for Ziihera plus chemotherapy [6] - The most common Grade 3 TRAE was diarrhea, occurring in 24.5% of patients receiving Ziihera plus tislelizumab and chemotherapy [6] Future Developments - Jazz Pharmaceuticals plans to submit Ziihera for FDA approval based on these results and is also evaluating Ziihera in other HER2-driven tumor types, including HER2-positive metastatic breast cancer [7][8] - An investor webcast is scheduled to discuss the Ziihera data presented at the ASCO GI symposium [8] Trial Details - The HERIZON-GEA-01 trial was a global, randomized, open-label study involving 914 patients across more than 30 countries, comparing Ziihera plus chemotherapy (with or without tislelizumab) to trastuzumab plus chemotherapy [9]

Core Insights - Roche, in collaboration with the Breast International Group (BIG) and other partners, announced significant overall survival results from the phase III APHINITY study for HER2-positive early-stage breast cancer, showing a 17% reduction in the risk of death after ten years for patients treated with a Perjeta-based regimen compared to those receiving Herceptin and chemotherapy [1][2][6]. Study Results - The APHINITY study demonstrated that 91.6% of patients treated with the Perjeta-based regimen were alive at ten years, compared to 89.8% for the control group, with a hazard ratio of 0.83 [6]. - A 21% reduction in the risk of death was observed in the subgroup of patients with lymph node-positive disease, with a hazard ratio of 0.79 [6][5]. - The previously reported invasive disease-free survival benefit was maintained, reinforcing earlier analyses [6][5]. Treatment Implications - The results validate the Perjeta-based regimen as a standard-of-care treatment for high-risk HER2-positive breast cancer patients, particularly those with lymph node-positive disease [2][4]. - Roche's commitment to improving outcomes for HER2-positive breast cancer patients is evident through the development of targeted therapies like Herceptin and Perjeta, which have transformed survival rates [11][10]. Future Presentations - Full results from the APHINITY study will be presented as a late-breaking abstract at the 2025 European Society for Medical Oncology Breast Cancer Congress [3].

Core Insights - Roche, in collaboration with Breast International Group (BIG) and other partners, announced significant overall survival results from the phase III APHINITY study for HER2-positive early-stage breast cancer, showing a 17% reduction in the risk of death after ten years for patients treated with a Perjeta-based regimen compared to standard treatment [1][5][6] Group 1: Study Results - The APHINITY study demonstrated that after ten years, 91.6% of patients treated with the Perjeta-based regimen were alive, compared to 89.8% of those receiving standard treatment, with a hazard ratio of 0.83 [6] - A 21% reduction in the risk of death was observed in the subgroup of patients with lymph node-positive disease, with a hazard ratio of 0.79 [6] - The previously reported invasive disease-free survival benefit was maintained, reinforcing earlier analyses [6] Group 2: Treatment Implications - The results validate the Perjeta-based regimen as a standard-of-care treatment for early-stage HER2-positive breast cancer, particularly for high-risk patients [1][3] - Roche's commitment to improving outcomes for HER2-positive breast cancer patients is evident through the development of targeted therapies like Herceptin and Perjeta, which have transformed survival rates [8][9] Group 3: Future Directions - Full results from the APHINITY study will be presented at the 2025 European Society for Medical Oncology Breast Cancer Congress, indicating ongoing research and collaboration in the field [2][5] - The collaborative efforts in the APHINITY study have led to pivotal trials that continue to enhance understanding and treatment of HER2-positive breast cancer [3][4]