- |||||||||| Enhertu (fam-trastuzumab deruxtecan-nxki) / Daiichi Sankyo, AstraZeneca
Clinical and genomic landscape of ERBB2 and ERBB3 mutated breast cancer (Hall 2-3) - Nov 4, 2023 - Abstract #SABCS2023SABCS_1852; We identify a notable enrichment of ERBB2/3-mut in lobular histology and metastatic tumors and tendency for co-alteration with CDH1 and multiple transcription factors reflecting the unique biology of ERBB2/3-mut breast cancers. Further analyses on an expanded cohort (n >6000 pts), including outcomes on HER2-directed antibody-drug conjugates (T-DXd) and targeted therapies such as PI3K inhibitors, will be presented at the 2023 SABCS Annual Meeting.
- |||||||||| letrozole / Generic mfg.
Ketogenic diet and letrozole to inhibit PI3K signaling in ER+ breast cancer (Hall 2-3) - Nov 4, 2023 - Abstract #SABCS2023SABCS_1060; For both groups, cell proliferation will be measured in a tumor biopsy obtained from the surgical specimen and compared with the pre-treatment diagnostic biopsy. Correlative studies will evaluate tumor markers of insulin/PI3K signaling before and after the intervention and between diet and control.
- |||||||||| SURVIVE study (Hall 2-3) - Nov 4, 2023 - Abstract #SABCS2023SABCS_654;
P=N/A The SURVIVE-study is a long-awaited trial in early breast cancer follow-up, based on promising liquid biopsy markers. If successful, the results will lead to a paradigm shift in current follow-up care of intermediate to high-risk early breast cancer survivors.
- |||||||||| LY294002 / Eli Lilly
Journal: The eNOS-induced leonurine's new role in improving the survival of random skin flap. (Pubmed Central) - Nov 3, 2023 And this protective function was inhibited by LY294002 (a broad-spectrum inhibitor of PI3K) and L-NAME (NG- nitro-L-arginine methyl ester, a non-selective NOS inhibitor)...By encouraging angiogenesis, preventing inflammation, minimizing oxidative stress, and lowering apoptosis, Leo can raise the survival rate of random skin flaps. The recommended concentration of Leo in this study was 30
- |||||||||| LY294002 / Eli Lilly, Ex-Rad (recilisib) / Onconova
Preclinical, Journal: Effects of the PI3K/Akt/HO-1 pathway on autophagy in a sepsis-induced acute lung injury mouse model. (Pubmed Central) - Nov 3, 2023 Preclinically validated combination therapies hold promise for NF2 patients and warrants further study in clinical trials. Furthermore, when PI3K inhibitors LY294002, PI3K activators Recilisib and hemin were administered before the surgery, Akt, p-Akt, HO-1, and LC3-II levels were measured 24
- |||||||||| pictilisib (GDC-0941) / Roche
Journal: A Novel Dual PI3K/mTOR Inhibitor, XIN-10, for the Treatment of Cancer. (Pubmed Central) - Nov 3, 2023 Meanwhile, through the results of protein blotting and PCR experiments, we concluded that XIN-10 can block the activation of the downstream pathway of mTOR by inhibiting the phosphorylation of AKT(S473) as well as having significant inhibitory effects on the gene exons of PI3K and mTOR. These results indicate that XIN-10 is a highly potent inhibitor with low toxicity and has a strong potential to be developed as a novel PI3K?/mTOR dual inhibitor candidate for the treatment of positive breast cancer.
- |||||||||| Venclexta (venetoclax) / Roche, AbbVie, Walter and Eliza Hall Institute
Computational Approach Based on Independent Drug Action Identifies Clinically Relevant Combinations for Acute Myeloid Leukemia (SDCC - Halls G-H) - Nov 3, 2023 - Abstract #ASH2023ASH_6482; After accounting for monotherapies that displayed pan-toxicity across healthy samples and primary AML samples (mean DSS > 95 th percentile), we found venetoclax as the top combination partner of the top 100 most effective predicted combinations (FPMTB, n = 33; Beat-AML, n = 35)...Our approach enables the major advantage of identifying effective combinations for the entire patient population as an alternative to personalized combinations. Further associations with genetic makeup and transcriptomics signature can be leveraged to identify suitable combinations.
- |||||||||| Venclexta (venetoclax) / Roche, AbbVie, Walter and Eliza Hall Institute
Clinical Outcomes in Patients Treated with Both Covalent Btkis and Venetoclax and the Significance of (SDCC - Halls G-H) - Nov 3, 2023 - Abstract #ASH2023ASH_6100; Pts with double refractory disease had a significantly shorter PFS and OS compared to others. These data are particularly relevant to clinical practice as they encourage participation in clinical trials and inform the design of trials investigating novel agents in this space.
- |||||||||| Imbruvica (ibrutinib) / AbbVie, J&J, AZD4573 / AstraZeneca
The Novel CDK9/CDK4/6/PI3K Triple Inhibitor LCI139 for the Treatment of MYC-Driven Mantle Cell Lymphoma (SDCC - Halls G-H) - Nov 3, 2023 - Abstract #ASH2023ASH_5610; Finally, we show that LCI139 overcomes chronic ibrutinib resistance by decreasing viability in JeKO-1 IR and Mino IR cells with an IC 50 of 79 nM and 89 nM, respectively. Therefore, the multitarget small molecule inhibitor LCI139 has superior potency against IR MCL cell lines and overcomes ibrutinib-resistance at nanomolar doses.
- |||||||||| Copiktra (duvelisib) / Secura Bio, Yakult Honsha
Duvelisib for Cytokine Release Syndrome Prophylaxis during CD19-Targeted CAR T Cell Therapy (SDCC - Halls G-H) - Nov 3, 2023 - Abstract #ASH2023ASH_4415; P1 Preliminary data from this study suggest that the addition of duvelisib to CAR T-cell therapy may prevent grade 3-4 CRS and also delay the onset of CRS. Although limited follow-up is available, the depth and duration of response is similar to published data for CAR T-cells in this setting.
- |||||||||| Lunsumio (mosunetuzumab) / Roche, Biogen
Marsun, a Phase III, Multicenter, Open Label, Randomized, Controlled Study Investigating Mosunetuzumab-Lenalidomide Versus Investigator Choices in Patients with Relapsed or Refractory Margin... (SDCC - Halls G-H) - Nov 3, 2023 - Abstract #ASH2023ASH_4013; Previous treatment lines must include at least one systemic line with a drug targeting CD20 (monoclonal antibody at least 2 cycles) with or without chemotherapy (CHOP, bendamustine, CVP, chlorambucil) or targeted treatment such as ibrutinib...For each patient, investigator choice must be decided before randomization between R-Len (12 cycles) and R-chemotherapy (R-Bendamustine or R-CHOP followed by a 6 months maintenance)...The study will comprise a first stage of 10 patients in a safety cohort with mosunetuzumab-lenalidomide followed by a stage 2 with patients randomized 1:1 to receive M-len or investigator choice (125 patients per arm). The sponsor of the trial is the Lymphoma Academic Research Organisation (LYSARC) in collaboration with GLA and FIL with the support of F.Hoffmann-La Roche Ltd.
- |||||||||| Jaypirca (pirtobrutinib) / Eli Lilly
Pirtobrutinib, a Highly Selective, Non-Covalent (Reversible) BTK Inhibitor in Relapsed/Refractory Follicular Lymphoma: Results from the Phase 1/2 BRUIN Study (SDCC - Halls G-H) - Nov 3, 2023 - Abstract #ASH2023ASH_3984; P1/2 Overall, 43 (90%) pts had received chemotherapy plus an anti-CD20 antibody, 17 (35%) pts had received a PI3K inhibitor, 14 (29%) pts had received lenalidomide, 6 (13%) pts had received an autologous stem cell transplant, and 4 (8%) pts had received CAR T-cell therapy. In this cohort of heavily pre-treated pts with R/R FL, pirtobrutinib showed potential efficacy and was well tolerated, including in pts with high risk FLIPI.
- |||||||||| Venclexta (venetoclax) / Roche, AbbVie, Walter and Eliza Hall Institute, Calquence (acalabrutinib) / AstraZeneca, Imbruvica (ibrutinib) / AbbVie, J&J
The Total Lifetime Cost of Treating Patients (Pts) with CLL in the United States (US) (SDCC - Halls G-H) - Nov 3, 2023 - Abstract #ASH2023ASH_2776; Our study highlights several equally effective therapy sequences to treat RR TNKL allowing therapy to be individualized based on patient and disease characteristics, and drug access at a given time. Tx categories included ibrutinib
- |||||||||| Venclexta (venetoclax) / Roche, AbbVie, Walter and Eliza Hall Institute, Aliqopa (copanlisib) / Bayer
A Phase I Study of Copanlisib and Venetoclax in Patients with Relapsed or Refractory Diffuse Large B-Cell Lymphoma (SDCC - Halls G-H) - Nov 3, 2023 - Abstract #ASH2023ASH_2155; P1/2 Copanlisib plus venetoclax is feasible and safe in pts with R/R DLBCL, with no DLTs observed. While it is possible that copanlisib plus venetoclax is active in select genomic subgroups of DLBCL, there was limited activity in this unselected, heavily pre-treated patient population.
- |||||||||| Itari (linperlisib) / Shanghai YingLi Pharma
A Phase Ib Study of Linperlisib Monotherapy in Patients with Relapsed or Refractory B-Cell Malignancies (SDCC - Halls G-H) - Nov 3, 2023 - Abstract #ASH2023ASH_2142; These encouraging results justify further investigation of linperlisib, both as a monotherapy and in combination with other therapeutic agents. It is hoped that these findings will help evolve and enhance our treatment strategies for B-cell malignancies and ultimately improve patient outcomes.
- |||||||||| Ezharmia (valemetostat) / Daiichi Sankyo, Aliqopa (copanlisib) / Bayer
Targeting Epigenetic Resistance Mechanisms to PI3 Kinase Inhibition in Leukemic Stem Cells (SDCC - Halls G-H) - Nov 3, 2023 - Abstract #ASH2023ASH_1833; Overall, our data suggests that PI3K plays an important role in leukemic stem cells, and that EZH2 downregulation is a non-genetic mechanism of resistance to PI3K inhibition. Additionally, our findings indicate that combining PI3K inhibitors with EZH1/2 dual inhibitors could be a promising therapeutic approach to reduce LSCs, prevent resistance, and prolong survival in AML patients.
- |||||||||| Jakafi (ruxolitinib) / Novartis, Incyte
Journal: Novel therapeutics in myeloproliferative neoplasms: beyond JAK inhibitors (Pubmed Central) - Nov 1, 2023 Ruxolitinib, a JAK1/2 inhibitor licensed for polycythemia vera and myelofibrosis, demonstrated efficacy in regulating hematocrit levels, lowering spleen volume, and relieving MPN-related symptoms...Furthermore, JAK inhibitors did not slow the progression of acute leukemia, indicating the need for new therapeutic methods for myelofibrosis. Novel medicines, including BCL inhibitor, MDM2 inhibitor, LSD1 inhibitor, PI3K inhibitor, BET inhibitor and telomerase inhibitor, are presently being evaluated in clinical studies for myelofibrosis with the potential to enhance clinical outcomes.
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