Inavolisib

FDA approves inavolisib (Itovebi) with palbociclib and fulvestrant for endocrine-resistant, PIK3CA-mutated, HR-positive, HER2-negative, locally advanced or metastatic breast cancer. INAVO120 trial showed median PFS of 15.0 months vs 7.3 months with placebo, and ORR of 58% vs 25%. Inavolisib recommended dose is 9 mg once daily.

Yuan Yuan discusses the rise of CDK4/6 inhibitors and ADCs in breast cancer treatment, highlighting uncertainties in eligibility, resistance, and sequencing. She mentions clinical trials like monarchE and NATALEE, and the importance of personalized radiation therapy and emerging ADCs. Yuan also addresses the need for research to understand drug resistance and the future of ADCs in breast cancer treatment.

Inavolisib (GDC-0077) showed a disease control rate (DCR) of 60% at 8 weeks and 32% at 16 weeks in patients with PIK3CA-mutated advanced solid tumors, with a favorable safety profile. The median progression-free survival was 3.52 months, and the 12-month overall survival rate was 51%. The most common adverse effects were hyperglycemia, diarrhea, fatigue, and constipation, mostly grade 1 or 2.

FDA reviews DFD-29 for rosacea, eladocagene exuparvovec for AADC deficiency, inavolisib for PIK3CA-mutated HR-positive breast cancer, acoramidis for transthyretin amyloid cardiomyopathy, and zanidatamab for HER2-amplified biliary tract cancer, with PDUFA dates in November 2024.

Novel anti-estrogen therapies, including PI3K pathway inhibitors like inavolisib, show promise in treating ER-positive advanced breast cancer, particularly in patients with PIK3CA mutations. These therapies, often used in combination with existing treatments like palbociclib and fulvestrant, aim to improve progression-free survival and overall outcomes. Personalized treatment strategies are evolving, focusing on identifying specific patient subgroups that may benefit most from these novel agents.

DelveInsight's 'Breast Cancer Pipeline Insight 2024' highlights a robust pipeline with 100+ companies developing 120+ drugs, driven by rising incidence, tech advancements, and increased awareness. Key companies and drugs include Ambrx, CSPC ZhongQi, Merus, and ARX788, DP303c, SHR-A1811, among others. FDA fast-track designations and breakthrough therapy designations for drugs like 9MW2821 and inavolisib underscore significant progress.

Roche agreed to pay $850 million to acquire two experimental breast cancer drugs from Regor Therapeutics. These 'next-generation' CDK inhibitors, RGT-419B and another in early trials, aim to improve upon current CDK treatments by addressing resistance and reducing side effects. Roche plans to start a Phase 2 trial for RGT-419B in 2024, with Regor managing ongoing Phase 1 trials and Roche handling further development and commercialization.

STX-478 is an oral, CNS-penetrant, allosteric inhibitor of mutant PI3Kα, targeting a cryptic pocket near the ATP-binding site, avoiding off-target effects on WT PI3Kα and other kinases.