6 Potential Practice-Changers Top Kantar's ASCO List

Stephanie Hawthorne, PhD

Research into 6 drugs scheduled to be presented during the upcoming 2016 ASCO Annual Meeting stand out as the most noteworthy abstracts on the docket this year because of their potential to influence clinical practice in the near future, according to Kantar Health, a leading healthcare and pharmaceutical industry advisory firm.

The list includes a novel chemotherapy compound for acute myeloid leukemia (AML), a first-in-class targeted agent for melanoma, and expanded findings about 2 checkpoint blockade immunotherapy drugs that have gained FDA approvals during the past 2 years.

More than 5200 abstracts have been selected for inclusion in the program for the annual meeting, which will be held June 3 to 7 in Chicago. Kantar Health’s “Top Presentations of Interest” were discussed by 3 experts who participated in an ASCO 2016 Preview webinar that the oncology information service OBR hosted last week. Other categories of interest were emerging research and later-stage disappointments.

“Our main driver to select this short list are those that are going to be able to have a near-term impact in the clinic,” said Stephanie Hawthorne, PhD, vice president of Clinical & Scientific Assessment at Kantar Health, during the OBR webinar. “That was a primary method—results with pivotal data that are going to lead either to a new market approval for a drug that’s not yet on that market or to a label expansion.”

Although most of the abstracts that will be presented are now available on the ASCO website, the findings reported in those documents represent older data gathered before the submission deadline in February, Michael King, managing director and senior biotechnology analyst at JMP Securities, noted during the OBR webinar. He cautioned that full data would be needed to reach conclusions about the research.

Listening to the full presentations to learn the “nuances” of the research being released is important for oncology specialists who look to the conference for practice-changing studies, agreed Lee S. Schwartzberg, MD, FACP, who offered a clinician’s view of the abstracts during the webinar. Schwartzberg is chief of Hematology Oncology at The University of Tennessee Health Science Center.

Here is a look at Kantar’s top 6 abstracts:

• CPX-351 (Vyxeos)—This chemotherapy agent is a liposomal formulation of cytarabine and daunorubicin that was tested among newly diagnosed, elderly patients (aged 60-75 years) with high-risk AML. The drug, developed by Celator Pharmaceuticals, is being evaluated for this patient population under the FDA’s breakthrough therapy program. In a phase III trial, CPX-351 demonstrated median overall survival (OS) of nearly 9.6 months compared with 5.6 months for a cytarabine/anthracycline combination, for a 31% reduction in the risk of death (HR, 0.69; P = .005), according to the ASCO abstract. The analysts will be looking for more details about the toxicity profile and outcomes among patient subsets. Abstract 7000.
• Binimetinib (MEK162)—This oral small molecule is a MEK inhibitor being developed for patients with melanoma harboring an NRAS mutation, an aberration for which there currently are no targeted therapies. Array Biopharma plans to submit findings from the phase III NEMO trial to the FDA for approval in NRAS-positive melanoma this year. In the study, binimetinib reached its primary endpoint of showing an improvement in progression-free survival (PFS), with a 2.8-month PFS for the novel compound in the intent-to-treat population compared with 1.5 months for dacarbazine (HR, 0.62; P <.001). Analysts will be looking for updated OS data. Abstract 9500.
• Daratumumab (Darzalex)—The CD38—targeting monoclonal antibody was granted an accelerated approval by the FDA in November 2015 for patients with multiple myeloma who have undergone ≥3 prior therapies. Results from the CASTOR study, one of the confirmatory trials required for full approval, are scheduled to be reported at ASCO. The phase III randomized trial evaluated daratumumab in combination with the standard regimen of bortezomib (Velcade) plus dexathemasone among patients who had received at least 1 prior line of therapy. Janssen, which is developing daratumumab in collaboration with Genmab, announced in March that the study would be stopped early after meeting its primary endpoint for PFS (P <.0001). Abstract LBA4.
• Nivolumab (Opdivo)—The PD-1 inhibitor, approved thus far in 4 tumor types, is being evaluated under a breakthrough therapy designation in patients with squamous cell carcinoma of the head and neck (SCCHN). Updated results from the phase III CheckMate-141 trial will be presented at ASCO. In the trial, 361 patients with cancer of the oral cavity, pharynx, or larynx were randomized in a 2:1 ratio to receive nivolumab (n = 240) or investigator's choice of cetuximab (Erbitux), methotrexate, or docetaxel (n = 121). Data reported earlier this year demonstrated median OS with nivolumab of 7.5 months compared with 5.1 months with investigator's choice of therapy (HR, 0.70; 95% CI, 0.51-0.96; P = .0101). Subgroup analysis by PD-L1 expression status is anticipated at ASCO. Abstract 6009.
• Pembrolizumab (Keytruda)—In another potential milestone in SCCHN, updated pembrolizumab data from the KEYNOTE-012 study will be presented. The FDA is evaluating the PD-1 inhibitor for patients with recurrent or metastatic SCCHN whose disease has progressed after platinum-containing chemotherapy, with a decision expected by August 9, 2016. The abstract indicates an ORR of 17.7% for pooled data from 192 patients, with responses varying based on whether participants harbor HPV. The ORR was 21.9% among HPV-positive patients and 15.9% among those with HPV-negative disease. Median OS is 8.5 months. Preliminary results from the KEYNOTE-055 study in patients who have progressed after platinum and cetuximab therapy also will be presented. Abstracts 6010-6012.
• Palbociclib (Ibrance)—The combination of palbociclib with letrozole has quickly become a first-line standard for postmenopausal women with ER—positive/HER2-negative advanced breast cancer following the FDA’s approval of the first-in-class CD4/6 inhibitor in February 2015. Updated primary data from the confirmatory phase III PALOMA-2 trial indicate that the median PFS with the palbociclib combination was 24.8 months compared with 14.5 months for letrozole plus placebo (HR, 0.58 [0.46—0.72]; P <.000001), according to the abstract. The combination demonstrated an ORR of 42.1% and a clinical benefit rate of 84.9%, compared with 34.7% and 70.3%, respectively, for the letrozole arm. Abstract 507.

Although the emphasis on the Kantar list was on the potential practice-changing abstracts, the conference also will feature interesting early data on emerging drugs with novel mechanisms of action, noted Hawthorne. These include research into these 8 drugs:

• Isatuximab (SAR650984)—An anti-CD38 monoclonal antibody in relapsed/refractory multiple myeloma (Abstract 8005)
• Sacituzumab govitecan (IMMU-132)—A Trop-2 antibody—drug conjugate in metastatic triple-negative breast cancer and metastatic non–small cell lung cancer (LBA509, Abstract 9011)
• Abemaciclib—A CDK4/6 inhibitor in hormone receptor—positive, HER2-negative breast cancer (Abstract 510)
• MOXR0916—An OX40 immune checkpoint agonist in advanced solid tumors (Abstract 101)
• PF-05082566—A monoclonal antibody targeting 4-1BB (CD137) protein receptor on T cells in advanced solid tumors (Abstract 3002);
• Rovalpituzumab tesirine (Rova-T)—A antibody—drug conjugate targeting DLL3 in recurrent or refractory small cell lung cancer (LBA8505)
• IMAB362—An antibody targeting the tight junction protein Claudin-18.2 in gastric and gastroesophageal junction cancer (LBA4001)
• ABT-165—A dual variable domain immunoglobulin molecule targeting DLL4 in the Notch pathway and VEGF in ovarian cancer (Abstract 2507)

Additionally, a number of clinical trials that were expected to produce pivotal findings failed to meet the hopes and expectations of the clinical trial sponsors. Kantar’s list of findings in this category include these 6 abstracts:

• Everolimus (Afinitor)—Adjuvant therapy in poor-risk diffuse large B-cell lymphoma (Abstract 7506)
• Sorafenib (Nexavar)—Combined with transarterial chemoembolization in localized, unresectable hepatocellular carcinoma (Abstract 4018)
• Cabazitaxel (Jevtana)—First-line metastatic castration-resistant prostate cancer (Abstract 5006)
• Trastuzumab emtansine (T-DM1; Kadcyla) plus pertuzumab (Perjeta)—Neoadjuvant, HER2-positive breast cancer (Abstract 500)
• Tremelimumab—Second- or third-line therapy for unresectable malignant mesothelioma (Abstract 8502)
• ADI-PEG20—A novel arginine deiminase (ADI) with polyethylene glycol as second-line therapy for hepatocellular carcinoma (Abstract 4017)

For more information about Kantar Health’s top ASCO picks, visit the OBR website at www.obroncology.com. Full abstracts are available on ASCO’s site at www.am.asco.org.