Novartis to present updates on broad cancer portfolio at ASH and SABCS symposiums

[News]

Novartis will present updates on its broad cancer portfolio with more than 240 abstracts at the upcoming American Society of Hematology (ASH) annual meeting and CTRC-AACR San Antonio Breast Cancer Symposium (SABCS).

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['lizbeth]

The first primary completion for the Phase III trial that I found was in October 2016 in the BELLE3 trial. It is exciting to see more options for hormone positive cancers - and in a Phase III.

BEZ235, Buparlisib (BKM120), AND BYL719

Inhibiting tumor proliferation and survival by blocking the phosphatidylinositol-3-kinase pathway

• Phosphatidylinositol-3-kinase (PI3K) and mammalian target of rapamycin (mTOR) are components of an intracellular signaling network, the PI3K-AKT-mTOR pathway, which regulates cellular metabolism, proliferation, and survival.1
• Abnormal activation of the PI3K-AKT-mTOR pathway has been validated as an important step toward the initiation and maintenance of human tumors by epidemiological and preclinical studies.1 This signaling cascade is also a key regulator of angiogenesis and upregulated metabolic activities in tumor cells.1
• Targeting the PI3K-AKT-mTOR pathway could arrest tumor growth and induce cell death in cancers that are resistant to currently available therapies.2-4
• BEZ235, BKM120, and BYL719 are oral, targeted anticancer compounds in clinical trials. BEZ235 is a PI3K/mTOR dual inhibitor5; BKM120 is a pan-PI3K inhibitor6; and BYL719 selectively inhibits PI3Kα. These compounds have shown cell growth inhibition and induction of apoptosis in a variety of tumor cell lines as well as in animal models.6-8 In addition, in preclinical models they have been shown to possess antiangiogenic properties.9,10 BEZ235 and BKM120 are currently being investigated in Phase I and II clinical trials in advanced solid tumor patients as a single compound as well as in combination with other compounds. BKM120 is also currently being investigated in Phase III or pivotal clinical trials in locally advanced or metastatic breast cancer patients in combination with other compounds. A single compound first-in-human study of BYL719 in advanced solid tumor patients is also ongoing.

All compounds are either investigational or studied in new indications. Efficacy and safety have not been established. There is no guarantee that they will become commercially available. MOA data based on in vitro/in vivo data. Clinical benefit is unknown.

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Updated: October 2013
References:

1. Wymann MP, Zvelebil M, Laffargue M. Phosphoinositide 3-kinase signalling – which way to target? Trends Pharmacol Sci. 2003;24(7):366-376.
2. Paez GP, Sellers WR. PI3K/PTEN/AKT pathway: a critical mediator of oncogenic signaling. Cancer Treat Res. 2003;115:145-167.
3. Liu P, Cheng H, Robert TM, Zhao JJ. Targeting the phosphoinositide 3-kinase pathway in cancer. Nat Rev Drug Discov. 2009;8(8):627-644.
4. Courtney KD, Ryan B, Engelman JA. The PI3K pathway as drug target in human cancer. J Clin Oncol. 2010;28(6):1075-1083.
5. Maira SM, Stauffer F, Brueggen J, et al. Identification and development of NVP-BEZ235, a new orally available dual PI3K/mTOR inhibitor with potent in vivo antitumor activity. Mol Cancer Ther. 2008;7(7):1851-1863.
6. Voliva CF, Pecchi S, Burger M, et al. Biological characterization of NVP-BKM120, a novel inhibitor of phosphoinosotide 3-kinase in Phase I/II clinical trials. Cancer Research. 2010;70(8 suppl 1):4498.
7. Serra V, Markman B, Scaltriti M, et al. NVP-BEZ235, a dual PI3K/mTOR inhibitor, prevents PI3K signaling and inhibits the growth of cancer cells with activating PI3K mutations. Cancer Res. 2008;68(19):8022-8030.
8. Engelman JA, Chen L, Tan X, et al. Effective use of PI3K and MEK inhibitors to treat mutant Kras G12D and PIK3CA H1047R murine lung cancer. Nat Med. 2008;14(12):1351-1356.
9. Schnell CR, Stauffer F, Allegrini PR, et al. Effects of the dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor NVP-BEZ235 on the tumor vasculature: implications for clinical imaging. Cancer Res. 2008;68(16):6598-6607.
10. Schnell CR, Arnal S, Becket M, et al. NVP-BKM120, a pan class I PI3K inhibitor impairs microvascular permeability and tumor growth as detected by DCE-MRI and IFP measurements via radio-telemetry: comparison with NVP-BEZ235. Cancer Research. 2010;7

0(8 suppl 1):4472.

[donocco]

Elizabeth

You've given me a lot of material
to study. I think LEE011 is also Novartis. It works like
Palbociclib as a CDK/4,6 inhibitor. I did some research
on it. The dose will probably be 600mg daily and the side effects are anemia, thrombocytopenia, lymphopenia, decreased appetite, fatigue, nausea, vomiting, diarrhea, decreased albumin concentration,
and possible increased blood sugar. Despite this list of
side effects it is considered a relatively safe drug and
may be an immediate rival to Palbociclib which, I think will be FDa approved
in a few years or earlier.

Paul

['lizbeth]

Paul,

Hopefully you will be overwhelmed keeping up with new cancer treatments over the next few years! Did you see all the treatments in the pipeline at Novartis?

I searched for Neoadjuvant trials a few months ago at clinicaltrials.gov and was just blown away at how many there were.

When do you expect any treatments that use targets other than the HER1-4 or ER+ to be approved?