Pre-conference insight: ASCO 2014.
By Joseph Hedden, Senior Analyst
15 May 2014
I am an analyst at Datamonitor Healthcare, having previously completed a PhD in Structural and Molecular Biology at Univ...
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Abstracts from the upcoming American Society of Clinical Oncology (ASCO) Annual Meeting (May 30-June 3) are now available. This year, the plenary session is lacking presentations about potential high-impact drugs in late-stage development or existing drugs in new indications. Datamonitor Healthcare has identified a number of other presentations at ASCO that will discuss therapies that have the potential to change cancer therapy in the future.
This video from Datamonitor Healthcare highlights the presentations we will be following closely, and why we think these are significant. These presentations will be discussed in depth after ASCO in our post-conference white paper.
The ongoing development of PD-1 and PD-L1 inhibitors
The presentation of the results from the Phase II study of MK-3475 (Merck) in the treatment advanced melanoma is likely to be of significant interest at ASCO 2014 (Abstract #LBA9000). The results of this trial formed the basis of MK-3475’s Biologics License Application for advanced melanoma (accepted by the FDA on May 6, 2014) and are likely to give an insight in to the commercial potential of MK-3475 in the melanoma market.
Also of interest will be a number of presentations discussing the activity of nivolumab (Bristol-Myers Squibb) in non-small cell lung cancer (NSCLC), renal cell cancer (RCC) and melanoma. In particular, the Phase I study of nivolumab in combination with Yervoy (ipilimumab; Bristol-Myers Squibb) for the treatment of metastatic RCC is likely to generate a lot of interest (Abstract #4504). Previous studies investigating combinations of immunotherapies have highlighted the potential clinical benefits of this treatment approach. It will be interesting to see how the results of this study in RCC compare with previous investigations into the activity of this combination therapy for the treatment of melanoma.
Close attention will also be paid to two presentations discussing the activity of MEDI-4736 (AstraZeneca) in a range of solid tumors (Abstracts #3001 and #3002). Despite the relatively small patient populations involved in the trials, these oral presentations are likely to give additional information about the commercial potential of MEDI-4736 should the Pfizer acquisition of AstraZeneca go ahead.
Imbruvica’s RESONATE results in chronic lymphocytic leukemia
Imbruvica (ibrutinib; Pharmacyclics) was granted accelerated approval in the US for treatment of relapsed or refractory chronic lymphocytic leukemia (CLL) in February 2014. The approval was based on the impressive overall response rate witnessed in patients in a Phase Ib/II study. Pharmacyclics are now looking to add the more comprehensive dataset from the Phase III RESONATE trial to Imbruvica’s label. On Tuesday at ASCO 2014, Pharmacyclics will present data from RESONATE for the first time (Abstract #LBA7008), and this is expected to be extremely positive. The data will give some insight into what potential competitors idelalisib (Gilead) and ABT-199 (AbbVie) need to show to be able to compete with Imbruvica, and help to provide a glimpse of what the future CLL treatment algorithm might look like.
Phase II data for blinatumomab in acute lymphocytic leukemia
Blinatumomab (Amgen) is a bispecific T-cell engaging (BiTE) antibody that directs cytotoxic T-cells to CD-19-expressing target cells. It is currently in Phase III development for relapsed/refractory Philadelphia chromosome- negative (Ph-) B-precursor acute lymphocytic leukemia (ALL). There are currently no targeted therapies for Ph- ALL, and uptake of cytotoxics at second-line is low due to high toxicities. On Tuesday at ASCO 2014, Amgen will present Phase II data that confirms blinatumomab has significant clinical activity in relapsed/refractory Ph- ALL patients (Abstract #7005). In this Phase II study, 43% of patients had a complete response to blinatumomab, showing it could become an important therapy option for this difficult-to-treat patient population.
Phase II data for Roche’s new antibody-drug conjugates in Non-Hodgkin’s lymphoma
An oral presentation on Saturday, May 31, will discuss the results of the Phase II ROMULUS trial that investigated polatuzumab vedotin (PoV) (Genentech/Roche/Seattle Genetics) and pinatuzumab vedotin (PiV) (Genentech/Roche/Seattle Genetics) in combination with Rituxan (rituximab; Genentech/Biogen Idec/Roche/Chugai) for the treatment of patients with relapsed and refractory non-Hodgkin lymphoma (NHL) (Abstract #8519). Both antibody-drug conjugates demonstrated acceptable clinical activity and tolerability in patients with diffuse large B-cell lymphoma (DLBCL), with patients receiving PoV and Rituxan demonstrating an overall response rate (ORR) of 51% and patients receiving PiV and Rituxan demonstrating an ORR of 54%. In patients with advanced follicular lymphoma (FL), PoV was found to be superior to PiV, with 30% of patients receiving PoV and Rituxan demonstrating a complete response.
With two antibody-drug conjugates currently marketed for the treatment of cancer, physician confidence in using this novel class of drugs is growing. The positive results demonstrated by PoV in the treatment of DLBCL and FL are likely to generate further interest in this class of drugs and their potential for the treatment of hematological malignancies.