Biotech Strategy Blog

Commentary on Science, Innovation & New Products with a focus on Oncology, Hematology & Cancer Immunotherapy

Posts tagged ‘Antibody Drug Conjugate’

Yesterday sudden and unexpected news from Seattle Genetics caused quite a stir…

“Seattle Genetics Announces Clinical Hold on Several Phase 1 Trials of Vadastuximab Talirine (SGN-CD33A).”

Part of the Seattle Genetics exhibit booth at #ASH16, taken with permission

In short, over 300 patients have been treated with the ADC and six experienced hepatotoxicity, including several cases of veno-occlusive disease, with four fatalities.

We’ve written about AML several times recently and also received a number of reader questions on this latest development, so it’s time to explore the issue in more depth and look at the implications. We also include some expert commentary from a leukemia specialist for their take on the issue.

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One of the overlooked highlights from ASCO this year was new data in diffuse large B cell lymphoma (DLBCL), which is an aggressive form of Non-Hodgkins Lymphoma (NHL). DLBCL is the most common form of NHL accounting for nearly one third of newly diagnosed NHL cases each year in the USA. Most of these people are adults rather than children.

The first sign of DLBCL is often a painless rapid swelling in the neck, armpit, or groin, which is caused by enlarged lymph nodes. Other symptoms can include night sweats, unexplained fevers, and weight loss.

Aggressive lymphomas such as DLBCL behave very differently from indolent NHL (iNHL) since they are faster growing and generally have a much poorer prognosis. As a result, they are treated much more aggressively with rituximab plus chemotherapy regimens such as CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone). Sometimes etoposide (E) is added in younger patients with a high disease burden, in which case the regimen is known as R-EPOCH.

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The cherry blossoms are finally blooming in Washington DC for the 2013 annual meeting of the American Association for Cancer Research (AACR).

With AACR in DC this year, the following traditional Japanese haiku published on the National Park Service website struck me as appropriate for cancer researchers and survivors to reflect on:

Yo no naka wa, Mikka minu ma ni, Sakura kana

“Life is short, like the three day glory of the cherry blossoms.”

Yesterday at AACR was predominantly an educational day, but several studies were highlighted to the assembled media.  One of the late-breaking clinical trials that caught my attention was the preliminary phase 1 data on Genentech’s novel new agent DMUC5754A.

Joyce Liu MD MPH. Photo: Dana-Farber Cancer Institute

Joyce Liu MD MPH

LB-290 Targeting MUC16 with the Antibody-Drug Conjugate DMUC5754A in patients with platinum-resistant ovarian cancer.  This data will be presented by Joyce Liu, MD, MPH from Dana-Farber Cancer Institute in the Clinical Trials Symposium on Tuesday, Apr 9 at 4.00 pm.

Dana-Farber issued a press release yesterday  – here’s the link. The picture of Dr Liu is from her Dana-Farber profile.

Ovarian cancer causes more deaths in women than any other cancer of the reproductive organs, with an estimated 20,000 women diagnosed with this cancer each year.  The majority of women are treated with traditional platinum based chemotherapies, and most of these relapse and develop drug-resistant disease.  This makes the development a new novel agent such as DMUC5754A that will treat platinum-resistant ovarian cancer a major potential breakthrough.

In an AACR media release, Dr Liu commented on how the drug works:

“This drug consists of an antibody and a potent toxin joined by a cleavable linker. The antibody identifies a protein, MUC16, which is highly expressed in ovarian cancers, and targets the toxin to kill the cancer cells.”

Liu went on to note that, “Unlike other cancer treatments, the antibody-drug conjugate releases the toxin with relative selectivity to the MUC16-positive cancer cells.  This allows delivery of drugs that would otherwise be too toxic for treatment.”

According to Liu, “If the activity of this drug is confirmed in additional trials, this will represent a novel type of therapy for ovarian cancer, with effectiveness in platinum-resistant ovarian cancer, which is the hardest type of ovarian cancer to treat.”

Genentech are particularly good at sharing early data at AACR, and based on the promising responses in MUC16 IHC 2/3+ patients, this new ADC compound is likely to progress to phase 2 – a compound to watch out for in the future.

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