Mining ASCO 2018's Gold, Part 5: There's A Lot To Look Forward To

by: Zach Hartman


Today's edition focuses on some potentially important developments in targeted therapy for various tumor types.

Daiichi Sankyo gets particular focus in this one.

Strong early results may give way rather quickly to pivotal studies for these agents.

The 2018 Annual Meeting of the American Society of Clinical Oncology (ASCO 2018) is upon us, and it's about as close to Christmas as I get in my line of work. There's so much data presented here, with thousands of abstracts delivered to an audience of some 30,000 healthcare professionals, that it's tough to keep up.

Of course, I'll be focused as you will on the big, high-profile presentations with obvious impact on investors over the next few months. But in order to make better forecasts about these companies, and in order to identify promising new leads on cancer investments, we need to pay attention to the smaller studies, as well.

This series includes 4 abstracts per day, but note that subscribers to the Total Pharma Tracker get a bonus abstract discussion. Learn more about this service here!

Basilea works in a chemotherapy prodrug for gynecologic cancers

Abstract 2529 - Phase 1/2a study of BAL101553, a novel tumor checkpoint controller (TCC), administered as 48-hour infusion in adult patients with advanced solid tumors.

Various solid tumors:

Basilea Pharmaceuticals (OTC:BPMUF)

BPMUF is a Swiss company with commercialized products in the anti-infection space, but they are also working on agents in cancer research. One of these agents, BAL101553 is a prodrug of a so-called “tumor checkpoint controller” inhibitor, which destabilizes microtubules to disrupt dividing cells. This phase 1/2a study assessed the safety and the recommended dosage for this agent. The phase 1 portion of the trial recruited 20 patients to receive various doses of BAL101553.

A maximal tolerated dose was identified for this agent, and in a second part of the phase 1 study, patients took the drug orally, achieving >80% bioavailability. Of 16 patients with evaluable disease, one response was observed in a patient with ovarian cancer, and 1 patient with endometrial cancer had stable disease. These findings suggest that the use of BAL101553 is feasible, with manageable toxicity, and it may have a clinical benefit for patients with certain gynecologic cancers. For now, it’s too soon to tell whether this drug will ultimately be successful, although several other early-stage studies are ongoing to identify potential indications.

Outlook: Neutral

Daiichi Sankyo builds against HER3

Abstract 2512 - Single agent activity of U3-1402, a HER3-targeting antibody-drug conjugate, in breast cancer patients: Phase 1 dose escalation study

Breast cancer

Daiichi Sankyo (OTCPK:DSKYF)

There are 4 members of the EGF receptor family, but, in cancer research, we tend to focus mainly on the first two: EGFR and HER2. But we are also gaining a better understanding of the third family member, HER3, which is an odd duck because of its willingness to form dimers not with itself but with other members of the EGFR family. And it is highly active in PI3K/Akt signaling, as well. So, it’s no surprise that companies are trying to exploit this receptor as a therapeutic target. DSKYF’s U3-1402 is an antibody-drug conjugate targeting HER3 and delivering a lethal payload to tumor cells. This phase 1/2 study focused on the use of this agent in metastatic breast cancer overexpressing HER3.

21 patients were included in the data analysis set, receiving a range of U3-1402 doses. Nausea and vomiting were the most common adverse events, and high-grade toxic events included thrombocytopenia and liver enzyme elevation, both reversible. 95% of the patients achieved disease control, and 33% responded outright. 17 of the patients remained on treatment as of the data analysis, 6 of whom has remained on treatment for over 6 months.

Overall, this preliminary analysis paints a favorable picture for the targeting of HER3 in this way. Since upwards of 18% of patients with breast cancer might be considered “HER3-positive,” this is an important early look at a potentially important treatment strategy in the coming years.

Outlook: Positive

Daiichi Sankyo shows promise in breast cancer antibody-drug conjugate development

Abstract 2501 - Trastuzumab deruxtecan (DS-8201a) in subjects with HER2-expressing solid tumors: Long-term results of a large phase 1 study with multiple expansion cohorts.

Various HER2-positive cancers

Daiichi Sankyo (OTCPK:DSKYF)

The realm of antibody-drug conjugates leaves many of us under the assumption that the most important piece of the equation is the antibody itself, as it directs the payload. Other pieces of the puzzle, such as the linker coupling the toxic drug to the antibody, as well as the toxic agent in question, often go unnoticed, as we civilians tend to do with chemotherapy. “It kills cells” is about all we want to know. However, DSKYF is developing a novel HER2 antibody-drug conjugate, trastuzumab deruxtecan, which used a different linker and chemotherapeutic from Roche’s (OTCQX:RHHBF) trastuzumab emtansine. Their report at ASCO focuses on the safety and efficacy of this new drug in a number of solid tumor expansion cohorts. This study enrolled 212 patients, demonstrating impressive response rates in HER2-positive breast cancer (64.2%) and gastric cancer (44.2%), as well as HER2-low breast cancer (38.5%) and other HER2-positive solid tumors (36.4%).

Obviously, we need to consider these results in the context of RHHBF’s drug. The EMILIA study was the first pivotal trial for trastuzumab emtansine, and it looked at HER2-positive metastatic breast cancer. The objective response rate in this study was 43.6%, with median progression-free survival of 9.6 months. The new conjugate yielded a median PFS of 10.4 months. Of course, we have to be careful about making cross-trial comparisons, especially considering EMILIA was reported 5 years ago, when the standard of care for HER2-positive breast cancer looked quite different. But still, these new findings are consistent with a promising therapy.

Outlook: Positive

Corcept looks to upend pancreatic cancer therapy

Abstract 2554 - A phase 1/2 study of relacorilant + nab-paclitaxel (nab-pac) in patients (pts) with solid tumors: The dose-finding phase

Various solid tumors

Corcept Therapeutics (CORT)

CORT is a developer of glucocorticoid receptor antagonists, and they have recently turned some of their attention to anticancer therapy. They are developing their agent relacorilant for use in solid tumors in combination with Celgene’s (NASDAQ:CELG) nab-paclitaxel. In this report, 25 patients were included in the analysis, most of whom had been exposed to a prior taxane. Neutropenia associated with the regimen was mitigable by growth factor support.

Responses and signs of disease control were observed in patients with ovarian cancer and pancreatic cancer, two tumor types where taxanes are currently standard treatment options. Interestingly, one patient with pancreatic cancer responded even though they had progressed on prior gemcitabine and nab-paclitaxel. These findings provide a tantalizing efficacy signal for relacorilant in combination with Abraxane, and the company is now planning expansion cohorts for pancreatic and ovarian cancer.

Outlook: Positive

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I wrote this article myself, and it expresses my own opinions. I am not receiving compensation for it (other than from Seeking Alpha). I have no business relationship with any company whose stock is mentioned in this article.

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