ASCO 2017 is nearly upon us, so here is the second of our blogs covering key data that will be released, this time in the latter part of the conference. As before, don’t forget to use our handy guides below on how to get around to these presentations while you’re there.
Results of adjuvant Perjeta (with Herceptin and chemotherapy) in HER2-positive breast cancer from the APHINITY trial. Abstract LBA500
APHINITY will be one of the biggest presentations to come out of ASCO 2017, not only in terms of the paradigm shift in treatment practice it may cause and the potentially huge number of patients it could impact, but also in terms of market impact and eventual revenues for the drug concerned, Perjeta. Back in March Roche announced the APHINITY trial had met its primary endpoint of invasive DFS, so the data are hotly anticipated. Perjeta's rapid uptake for metastatic HER2-positive breast cancer as well as its neoadjuvant approval has meant the agents sales reached almost $2 billion in 2016 globally; considering the bulk of Herceptin's $7 billion sales are derived from the adjuvant HER2-positive breast cancer setting, if the data from APHINITY supports regulatory approval of Perjeta in this population it could prove a big win for Roche. Making the data even more interesting is the recent 12-4 ODAC vote that another drug, Puma Biotech’s neratinib, has a risk-benefit profile sufficient to support its use as an extended adjuvant therapy following adjuvant treatment with the current standard of care, Herceptin.
Results from the ALEX trial of Alecensa vs. Xalkori in advanced first-line ALK-positive NSCLC. Abstract LBA9008
Results from the ALEX trial were widely anticipated after Roche's announcement in April that Alecensa met its primary endpoint of PFS. The trial evaluates Alecensa head-to-head against the standard of care Xalkori in the first-line setting, and is therefore hugely significant for the management of ALK+ NSCLC patients. Back in February 2016, Alecensa had also demonstrated superiority over Xalkori in the smaller, Japanese J-ALEX trial. The results from the ALEX study are expected to support the first-line label expansion of Alecensa for ALK+ NSCLC. Based on the positive data, Alecensa is well-poised to largely displace Xalkori in the first-line setting and will thus generate significant sales for Roche exceeding $1.5 billion.
Data on Keytruda in bladder cancer. Abstract 4501, 4502, 4530
Earlier this month, the FDA granted approval to Keytruda for platinum pre-treated advanced/metastatic bladder cancer, and simultaneously granted accelerated approval for Keytruda as a first-line therapy in the disease. Approval in the recurrent setting is based on KEYNOTE-045, and two presentations from this trial at ASCO (one on OS analysis and another on quality of life), could prove key in giving Keytruda the edge it needs to get ahead of other immune checkpoint inhibitors already approved in this setting. Keytruda’s accelerated approval in first-line bladder cancer, based on the phase II KEYNOTE-052 trial, has made it the second agent of its class to enter this setting after Tecentriq. However, confidence in Tecentriq has taken a knock after it failed to confirm its efficacy benefits in a Phase III trial in the recurrent population, meaning the presentation of Keytruda’s KEYNOTE-052 data at ASCO give it the opportunity to rally support and confidence among prescribers.
Data from ZUMA-3 of the CAR T-cell therapy, KTE-C19 in high-burden relapsed/refractory ALL. Abstract 3024
Kite's ZUMA-3 and 4 trials continue development of their lead CAR T-cell candidate, KTE-C19, in relapsed or refractory ALL. Initial efficacy results from ZUMA-3 were previously announced in December 2016 and proved encouraging, with over 80% of this difficult to treat population responding to treatment. However, there are ongoing safety concerns following announcement of the death of one ZUMA-3 trial participant from cerebral edema. This has drawn ongoing comparisons to Juno's ill-fated JCAR-015, which was shelved last year due to similar problems with patient safety. Thus far, KTE-C19's safety profile has not been as problematic as that for JCAR-015, but stakeholders will be keen to know how the efficacy and safety profiles hold up in a larger trial population. If these updated results from ZUMA-3 confirm KTE-C19's efficacy, it could eventually lead to approval in ALL and impact CAR T-cell development methodology going forward.
If you’re interested in learning more about CAR T-cell therapy, check out our free Executive Briefing on the topic, here.
Data on epacadostat plus Keytruda in solid tumors from ECHO-202/KEYNOTE-037. Abstract 4503, 4515, 4503, 6010, 9014
Combination regimens involving immune checkpoint inhibitors are a very active area of oncology drug development. Among these, the combination of PD-1 inhibitor Keytruda and IDO inhibitor epacadostat has shown promising data in early phase trials in malignant melanoma. The results of the ECHO-202/KEYNOTE-037 are highly anticipated as an indicator of the combination's potential in other tumor types, including NSCLC, renal cell carcinoma, bladder cancer, SCCHN, triple-negative breast cancer, and ovarian cancer. Earlier this month 2017 Incyte published a press release indicating that the combination has encouraging activity in NSCLC (ORR 35%), SCCHN (ORR 31%), bladder cancer (ORR 35%) and renal cell carcinoma (ORR 30%), and that the combination was well-tolerated. Improving response rates in these indications is highly desirable and will bring significant commercial rewards. The safety and efficacy profile of the combination is even more important to watch after the recent approval of the first immune checkpoint inhibitor plus chemotherapy combination in NSCLC (Keytruda + Alimta + carboplatin). Further updated data from the ECHO-202/KEYNOTE-037 trial for the multiple tumors are to be presented at ASCO 2017, and pivotal trials for the Keytruda and epacadostat combination are expected to be announced soon.
Enasidenib in mutant-IDH2 relapsed or refractory AML. Abstract 7004
Enasidenib (AG-221), a selective inhibitor of mutated IDH2 protein which occurs in 8-15% of AML patients, is being evalauted in a phase I/II AG221-C-001 study, based on which Agios Pharma have filed for FDA approval for treatment of IDH2 mutated relapsed/refractory AML patients. First results from this trial were presented at ASH 2015, data from which helped the agent receive Priority Review; enasidanib’s PDUFA date is set for August 30, 2017. The latest data from this trial which will be presented at ASCO 2017 show an improvement in response rates (ORR of 40%, including CR of 19%), albeit for a short duration (mDoR of 5.8 months). AML patients who have relapsed or are refractory to first-line treatment are notoriously difficult to treat, and there is no standard of care in this setting, meaning these updated data and the looming PDUFA date are keenly anticipated.
Data on Bosulif as a first-line therapy in CML. Abstract 7002
In December 2016 Pfizer and Avillion announced top-line positive results from the BFORE trial, a Phase III study of Bosulif in first-line philadelphia chromosome (Ph+) positive CML. Bosulif already holds approval as a therapy in the U.S. and Europe for Ph+ patients who previously received a TKI, and the results of BFORE could lead to a label expansion for Bosulif into a new treatment setting. Bosulif met the primary endpoint of this trial, MMR at one year, an endpoint which has supported first-line approval of Tasigna and Sprycel in this setting. Bosulif lead to higher rates of some toxicities over imatinib treatment, so it will be interesting to see the discussion of these data, and whether Bosulif's they are strong enough to support a move into first-line CML.
Decision Resources Group will be at ASCO 2017 at booth #22115 in the Exhibitors Hall, we look forward to seeing you there!