Asco preview – Proven approaches have their day
Immunotherapy has sparked most of the excitement surrounding the world’s biggest oncology conference for three years running, but 2016 is shaping up to be a year for more familiar agents.
It is not as though checkpoint inhibitors and modified T cell therapies are not in active and urgent study – it is that the next wave of data is in an array of combinations for the former, and in some key mid-stage readouts for the latter. As such, kinase inhibitors, targeted antibodies and mainstay chemotherapies will be receiving a great deal of the attention when Asco convenes later this week in Chicago.
As a sign, look no further than news last week that a phase III study of Roche’s CD-20 targeting cytotoxic antibody Gazyva in indolent non-Hodgkin lymphoma had been stopped early because of clear superiority to Rituxan. This should help the Swiss group hold its own against Rituxan biosimilars and help Gazyva achieve peak sales in the $3-4bn range, according to analysts from Berenberg.
While that set of Gazyva data from the Gallium trial will not be featured, the design of the Oasis trial that combines it with Imbruvica and Venclexta will be discussed, along with data on a combination of Venclexta, Rituxan or Gazyva, and the three-drug chemotherapy protocol called Chop.
Small molecule advances
The cyclin-dependent kinase (CDK) 4 & 6 inhibitor class will have a place of honour in this year’s Asco presentations, with breast cancer data from the three main contenders – Pfizer’s Ibrance, Eli Lilly’s abemaciclib, and Novartis’s ribociclib – making waves.
The Paloma-2 trial data, part of an oral abstract session on Monday, will show off the improvements in progression free survival offered by the Pfizer drug, while abemaciclib’s phase II monotherapy trial Monarch 1 is a late breaking abstract discussed in a clinical science symposium on Friday (Asco preview – Two directions for novel small-molecule classes, May 19, 2016).
Leerink analyst Seamus Fernandez described the Monarch 1 results – yielding an objective response rate of 17.4% – as “good, but not great” and said the response rate “falls below FDA's threshold for accelerated approval.”
The biggest presentation on ribociclib, formerly known as LEE011, will outline a trial's design rather than results. The front-line Monaleesa-3 trial in combination with fulvestrant could read out by year’s end. The first-line Monaleesa-2 trial, results of which came too late for Asco, showed combining with letrozole could extend progression free survival compared with letrozole alone, so Monaleesa-3 has a decent chance of also succeeding (Novartis first to make pre-Asco splash, May 18, 2016).
Parp inhibitors will reinforce their place as a treatment for ovarian cancer, but not much beyond that, as disappointing results were seen outside this space. In ovarian disease, however, the parp inhibition thesis looks strong, as AstraZeneca has disclosed overall survival data when Lynparza is used after platinum therapy – overall survival was significantly improved over placebo for all patients, and in patients with a BRCA mutation the effect was more pronounced.
Immuno-oncology and more
Recent editions of this conference have shown the progress of the immuno-oncology approach, and with all the attention being paid, it is inevitable that some of these agents will take the spotlight this year too. Three-year survival data for patients treated with the PD-1 antibody Keytruda in advanced melanoma have already been released pre-conference, with researchers concluding, as has been previously shown, that a small subset of patients has durable response.
Roche’s Tecentriq, which similarly works on the programmed death-1 pathway, will also have a prime presentation place when results from a cohort of bladder cancer patients in the IMVigor 210 trial are disclosed. The Swiss group revealed a broad swathe of data from this trial at the 2015 European Cancer Congress (ECC – Roche puts the atezo pieces together, September 28, 2015).
Similarly, the antibody-drug conjugate rovalpituzumab tesirine (rova-T), for which AbbVie paid $5.8bn in late April, will have its US debut after premiering on the European stage at ECC, with late-breaking data in small-cell lung cancer (AbbVie caps week of cancer deals with huge Stemcentrx takeout, April 29, 2016). AbbVie investors, of course, will look closely at the data for signs as to whether the Illinois-based company’s spending spree is getting value for money.
And speaking of private groups with high-profile data readouts, Ganymed Pharmaceutical will have its anti-claudin 18.2 antibody IMAB362, or claudiximab, as a late-breaking study in gastroesophageal junction adenocarcinoma. Should these data be as compelling as rova-T’s, the sector could see a similar billion-plus-dollar takeout of the German group.
Finally, it would not be a cancer congress of late if some data from trials of adoptive T cell therapies were not in the spotlight. Kite Pharma and the National Cancer Institute’s cooperative phase I study of anti-CD19 CAR-T cell therapy will feature as a late-breaking study in advanced diffuse large B-cell lymphoma.
While the sector awaits the next wave of immuno-oncology advances, late-stage progress with targeted small molecule agents and even refinements in old-fashioned chemotherapies are being seen. This serves as a reminder that older approaches have not lost their relevance, and do much of the hard work in cancer treatment.
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