Memorial Sloan Kettering Cancer Center

Arcus Biosciences and AstraZeneca collaborate on a clinical trial to evaluate the combination of Arcus's HIF-2a inhibitor casdatifan and AstraZeneca's PD-1/CTLA-4 bispecific antibody volrustomig in clear cell renal cell carcinoma patients. This is their second collaboration, following the 2020 PACIFIC-8 trial. Arcus also shares positive results from the Phase II EDGE-Gastric study, showing improved progression-free survival with domvanalimab plus zimberelimab and chemotherapy in upper GI cancers.

NSCLC with HER2 mutations, found in 3% of advanced non-squamous cases, is associated with poor prognosis and higher incidence of brain metastases. Standard first-line chemotherapy has limited efficacy, and HER2-targeted agents lag in NSCLC treatment. Recent studies using HER2 TKIs, ADCs, and monoclonal antibodies show promising results, with Trastuzumab deruxtecan (T-DXd) achieving 55% ORR and 8.2 months mPFS in DESTINY-Lung01 trial. Zongertinib, a novel HER2-specific TKI, demonstrated 62% ORR and 97% DCR in HER2 mutation-positive NSCLC patients, with low toxicity rates, suggesting a potential better tolerated treatment option.

The Cancer AI Alliance (CAIA) brings together scientists from Johns Hopkins to develop AI-driven precision cancer care strategies, addressing challenges in data analysis and privacy compliance. CAIA aims to provide computational infrastructure for processing high volumes of cancer data, fostering interdisciplinary collaboration and ensuring data security.

Part B of CheckMate 914 trial showed no disease-free survival benefit with adjuvant nivolumab vs placebo in high-risk localized renal cell carcinoma patients post-nephrectomy, consistent with Part A results. Median disease-free survival was not reached in nivolumab or placebo groups, with 18-month rates of 78.4% vs 75.%, respectively (HR = 0.87, 95% CI = 0.62–1.21, P = .40). Grade 3 to 4 adverse events were reported in 17.2%, 15.0%, and 28.9% of patients given nivolumab, placebo, and nivolumab/ipilimumab, respectively.

A multicenter study reveals KRAS gene mutations in pancreatic ductal adenocarcinoma (PDAC) impact survival rates, with KRAS-G12D linked to aggressive cancer and worse outcomes, while KRAS-G12V and KRAS-G12R associated with better survival. The findings suggest clinical guidelines should include routine molecular testing for all pancreatic cancer patients.

The phase III PSMAfore trial, reported in The Lancet by Morris et al., demonstrated improved progression-free survival with lutetium-177–labeled PSMA-617 (LuPSMA) compared to a change in androgen receptor pathway inhibitor (ARPI) in taxane-naive patients with metastatic castration-resistant prostate cancer. Median radiographic progression–free survival was 9.30 months with LuPSMA vs 5.55 months with ARPI change, with a favorable safety profile. The study concluded that LuPSMA may be an effective treatment alternative for PSMA-positive patients considering ARPI change after progression on a previous ARPI.

A study finds KRAS gene mutations in pancreatic ductal adenocarcinoma (PDAC) vary, with KRAS-G12D linked to aggressive cancer and poor outcomes, while KRAS-G12V and KRAS-G12R associated with better survival. The research suggests clinical guidelines should be revised to include routine molecular testing for all pancreatic cancer patients.

Kazia Therapeutics reported a 67% partial response rate with 45mg paxalisib and radiotherapy in a Phase I study for solid tumor brain metastases with PI3K pathway mutations, presented at ASTRO 2024. Over two-thirds of patients at maximum tolerated dose achieved intracranial response, suggesting paxalisib's potential in overcoming tumor radioresistance.

Dr. Dana Rathkopf discusses BMS-986365, a dual-action androgen receptor degrader and inhibitor for prostate cancer, presenting phase I/II trial data showing efficacy, particularly in patients without prior chemotherapy, and a manageable side effect profile, including QTC prolongation. The drug's potential to overcome resistance to AR pathway inhibitors and its tolerability are highlighted.

Study investigates pre-operative mRNA-based models for predicting biochemical recurrence (BCR) in prostate cancer, finding machine learning (ML) models, particularly random survival forest (RSF) and boosted Cox models, significantly outperform traditional nomograms. mRNA variables like DNAH8, ABCC11, ESM1, and PI15 show potential as biomarkers for early treatment decisions, paving the way for precision medicine approaches.