Adavosertib

Adavosertib Shows Promise in Uterine Serous Carcinoma Despite Tolerability Challenges

15 days ago

• The phase 2b ADAGIO trial demonstrated adavosertib's antitumor activity with a 26% objective response rate in patients with recurrent or persistent uterine serous carcinoma, though median progression-free survival was only 2.8 months. • Treatment-related adverse events were significant, with 97.2% of patients experiencing side effects and 60.6% experiencing grade ≥3 events, leading to treatment discontinuation in 17.4% of patients. • Despite tolerability challenges, researchers believe WEE1 inhibition remains a promising therapeutic target for uterine serous carcinoma, with exploratory biomarker studies suggesting CCNE1 amplification may predict better response.

Schrödinger Unveils Promising Preclinical Data for Novel Cancer Therapeutics at AACR 2025

2 months ago

• Schrödinger presented preclinical data for SGR-3515, a Wee1/Myt1 co-inhibitor showing superior anti-tumor activity compared to monotherapy inhibitors, with optimized dosing schedules that preserve efficacy while minimizing side effects. • The company revealed first characterization data for SGR-4174, a selective SOS1 inhibitor targeting KRAS-driven cancers, demonstrating potent tumor growth inhibition both as monotherapy and in combination with MEK or KRAS inhibitors. • Initial Phase 1 clinical trial data for SGR-3515 in patients with advanced solid tumors is expected in the second half of 2025, highlighting Schrödinger's progress in translating its computational drug discovery platform into clinical candidates.

Phase IIb ADAGIO Trial: Adavosertib Shows Limited Efficacy with High Toxicity in Uterine Serous Carcinoma

4 months ago

• The Wee1 inhibitor adavosertib demonstrated modest activity with a 26% objective response rate in patients with recurrent or persistent uterine serous carcinoma in the phase IIb ADAGIO trial. • Treatment was associated with significant toxicity, with 97.2% of patients experiencing treatment-related adverse events and 60.6% experiencing grade ≥3 events, leading to treatment discontinuation in 14.7% of patients. • Biomarker analysis suggested CCNE1 amplification and high cyclin E1 protein expression may predict better response to Wee1 inhibition, potentially informing future drug development despite adavosertib no longer being in clinical development.

Eflornithine (Iwilfin) Approved for High-Risk Neuroblastoma to Reduce Relapse Risk

6 months ago

• Eflornithine (Iwilfin) is now FDA-approved to reduce the risk of relapse in high-risk neuroblastoma patients who have shown partial response to prior therapies. • The approval was based on a Phase II trial demonstrating significantly improved event-free survival and overall survival compared to historical controls. • Eflornithine inhibits polyamine synthesis, targeting the MYCN oncogene, which is crucial in neuroblastoma development and progression. • Common adverse effects include otitis media, sinusitis, pneumonia, and diarrhea, necessitating careful monitoring and management of patients on eflornithine.

Mathematical Model Identifies PARP Inhibitor Resistance Biomarkers in Triple-Negative Breast Cancer

6 months ago

• A novel mathematical model was developed to analyze tumor growth dynamics in triple-negative breast cancer (TNBC) patient-derived xenografts treated with olaparib. • The model identifies the pre-treatment resistance fraction as a key predictor of response to olaparib, distinguishing complete responders, initial responders, and non-responders. • Correlation analysis reveals potential biomarkers within the CIViC gene list, offering insights into mechanisms driving resistance to PARP inhibitors. • The study highlights the utility of mathematical modeling in identifying predictive biomarkers and understanding complex drug response patterns in cancer.

Advances in PARP Inhibitor Combinations Show Promise for Ovarian Cancer Treatment

3 years ago

• Recent research demonstrates that combining PARP inhibitors with targeted therapies like ATR inhibitors and WEE1 inhibitors shows potential in overcoming PARP resistance in ovarian cancer patients. • Studies reveal that PARP inhibitor combinations with antiangiogenic agents and immunotherapy agents are showing encouraging results, particularly in specific patient subgroups. • Multiple clinical trials are currently evaluating novel combination strategies to enhance PARP inhibitor efficacy in both homologous recombination deficient and proficient tumors.

FDA Grants Fast Track Status to BBO-8520 for KRAS G12C-Mutated NSCLC

5 years ago

• The FDA has granted fast track designation to BBO-8520, an oral agent under investigation for treating KRAS G12C-mutated metastatic non-small cell lung cancer. • This designation aims to expedite the development and review of BBO-8520, addressing an unmet need in previously treated NSCLC patients. • The decision was based on the drug's potential to improve outcomes in this specific genetic subgroup of lung cancer, where treatment options are limited.