ASCO Highlights Include Phase III Findings in Multiple Tumor Types

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Findings from large, late-stage clinical trials in melanoma, nonâ€“small cell lung cancer, and several hematologic malignances are expected to rank among the most clinically significant research findings presented at the 2015 American Society of Clinical Oncology Annual Meeting.

Findings from large, late-stage clinical trials in melanoma, non—small cell lung cancer (NSCLC), and several hematologic malignances are expected to rank among the most clinically significant research findings presented at the 2015 American Society of Clinical Oncology (ASCO) Annual Meeting, according to industry analysts.

In keeping with the trend over the past several years, immunotherapies will attract much interest at this year’s conference, which opens Friday in Chicago. The checkpoint inhibitors nivolumab (Opdivo) and ipilimumab (Yervoy) are generating the most attention in this class of therapy but emerging monoclonal antibodies with immunogenic qualities also register among the highlights.

With more than 5000 abstracts presented during the conference, pharmaceutical industry analysts have been combing the data for clues that will affect the financial fortunes of the companies developing the drugs. One biotech saw its stock plunge after ASCO took the wraps off the abstracts in mid-May and other companies are likely to find their market positions enhanced or damaged when the data are fully presented. For late-breaking abstracts, data will be released shortly before the presentation.

Kantar’s Top Abstracts List

Experts from Kantar Health, a market research firm based in New York City, have identified 10 abstracts involving nine different agents for its Top Presentations of Interest to be presented at this year’s conference (https://goo.gl/eLXPja). All of the entries on the list concern phase III clinical trial data. Here is a snapshot of that research, with the corresponding abstract numbers:

Nivolumab and Ipilimumab—Researchers will report survival data from two phase III trials involving the PD-1—targeting immunotherapy agent in NSCLC and another study in which the drug was combined with ipilimumab in melanoma. Nivolumab already is approved in both those tumor types; the new data are expected to provide a more extensive picture of its efficacy in NSCLC and the potential to improve outcomes in melanoma by pairing the drug with the CTLA-4-targeting ipilimumab. CheckMate-017 compared nivolumab with docetaxel as second-line therapy among 272 patients with squamous cell NSCLC (Abstract 8009), while CheckMate-057 evaluated the agent as second-line therapy in advanced nonsquamous NSCLC (Abstract LBA109). Positive results are anticipated from both trials, particularly CheckMate-057, which developer Bristol-Myers Squibb said was halted early after meeting its primary overall survival endpoint. In the CheckMate-067 trial, initial efficacy and safety data will be presented for the combination of nivolumab plus ipilimumab as a first-line treatment for patients with advanced melanoma (Abstract LBA1). The phase III trial was launched after the combination achieved promising results in an earlier clinical trial.
Ibrutinib (Imbruvica)—The Bruton tyrosine kinase inhibitor has garnered FDA approvals for four indications in hematologic malignancies since its initial approval in November 2013, including as second-line therapy in chronic lymphocytic leukemia (CLL) and as a first-line option for patients with CLL that harbors a chromosomal 17p deletion. In the phase III HELIOS trial, the combination of ibrutinib with the standard-of-care rituximab (Rituxan) plus bendamustine (Treanda) is being compared with placebo plus rituximab/bendamustine in 578 patients with relapsed/refractory CLL and with small lymphocytic leukemia. Janssen Research & Development, which developed the drug along with Pharmacyclics, announced in March that the ibrutinib-containing regimen met its primary endpoint of improving progression-free survival (PFS). Full topline results are expected to be disclosed at ASCO (Abstract LBA7005).
Pemetrexed (Alimta)—The phase III PROCLAIM trial evaluated whether the addition of pemetrexed to standard chemoradiotherapy improves overall survival in patients with stage III unresectable nonsquamous NSCLC. Results will be reported for 555 patients randomized to receive pemetrexed plus cisplatin and radiotherapy followed by consolidation pemetrexed versus etoposide plus cisplatin and radiotherapy followed by physician’s choice consolidation chemotherapy (Abstract 7506).
Palbociclib (Ibrance)—Less than 4 months ago, the first-in-class CDK4/6 inhibitor was approved in combination with letrozole for the treatment of postmenopausal women with estrogen receptor—positive, HER2-negative metastatic breast cancer as initial endocrine-based therapy. In the phase III PALOMA-3 trial, palbociclib combined with fulvestrant (Faslodex) was compared with fulvestrant alone among 521 enrolled patients with hormone receptor–positive, HER2-negative disease that progressed after prior endocrine therapy (Abstract LBA502). In April, Pfizer disclosed that PALOMA-3 was stopped early because the study met its primary endpoint of statistically improving PFS.
Obinutuzumab (Gazyva)—The anti-CD20 IgG1 monoclonal antibody is being groomed as a successor to rituximab, a bedrock therapy in several hematologic malignancies. In the phase III GADOLIN trial, 413 patients with rituximab-refractory indolent non-Hodgkin lymphoma were randomized to receive obinutuzumab plus bendamustine versus bendamustine alone (Abstract LBA8502). Genentech, a Roche Group member that is developing the drug, said in February that the trial was stopped early because it had met its PFS endpoint and that the data would be submitted to the FDA to support a new indication. The drug currently is approved in combination with chlorambucil for patients with CLL.
Carfilzomib (Kyprolis)—The phase III ENDEAVOR trial pits the second-generation proteasome inhibitor carfilzomib against bortezomib (Velcade), the first agent in this class, in 929 patients with relapsed multiple myeloma (Abstract 8509). Patients were randomized to receive either drug in combination with dexamethasone, with PFS as the primary endpoint. Carfilzomib was approved in 2012 as a third-line therapy for patients with progressive multiple myeloma, and results of the ENDEAVOR trial may help move the drug forward in the treatment timeline, Kantar analysts noted. Amgen, which acquired Onyx Pharmaceuticals, is developing the agent.
Elotuzumab—The addition of the investigational SLAMF7 monoclonal antibody to a regimen of lenalidomide (Revlimid) plus dexamethasone is emerging as a new treatment option for patients with relapsed/refractory multiple myeloma as a result of the phase III ELOQUENT-2 trial, researchers said in discussing the findings in an ASCO-sponsored premeeting press conference (Abstract 8508). The study randomized 646 patients to the elotuzumab-containing regimen or lenalidomide plus dexamethasone alone. The elotuzumab arm demonstrated a 30% reduction in the risk of disease progression, investigators said. The FDA has designated this agent as a breakthrough therapy and, if approved, elotuzumab would be the first monoclonal antibody available in multiple myeloma. Bristol-Myers Squibb and AbbVie are collaborating on developing the drug.
Neratinib—Hopes had been high that neratinib, a tyrosine kinase inhibitor that targets EGFR and HER2, would provide a new adjuvant therapy option after chemotherapy and trastuzumab (Herceptin) in patients with early-stage HER2-postive breast cancer. In the phase III ExteNET trial, 2821 patients were randomized to receive either neratinib or placebo as follow-up to adjuvant trastuzumab. The 2-year data in the ASCO abstract released in mid-May (Abstract 508) showed an advantage for neratinib, but the difference in invasive disease-free survival was smaller than investors had anticipated and drug developer Puma Biotechnology saw its stock plummet nearly 20% overnight. The stock has since regained much of that ground to close at $198.52 per share Tuesday on the New York Stock Exchange.

Emerging Agents Showcased

While Puma Biotechnology’s experience provides a dramatic example of the ways in which ASCO abstracts can affect a company’s prospects in the marketplace, the conference offers an opportunity for pharmaceutical developers throughout the world to shine a spotlight on their research programs.

In addition to the late-stage clinical trial findings that Kantar cited, there are many studies that are expected to help physicians determine optimal uses for established and emerging compounds. Here are some of the agents that oncology thought leaders, analysts, and the companies themselves consider noteworthy:

MEDI4736—Safety and efficacy data will be reported from a clinical trial in which the PD-1 inhibitor is paired with tremelimumab, which targets CTLA-4, in patients with NSCLC (Abstract 3014). AstraZeneca, which is developing the drug through its MedImmune research arm, has obtained a fast-track designation from the FDA for MEDI4736 as monotherapy for patients with advanced NSCLC.
Daratumumab—Results from the phase II Sirius study of daratumumab monotherapy in patients with multiple myeloma who have received ≥3 lines of prior therapy or whose disease is double refractory to a proteasome inhibitor and an immunomodulatory drug will be presented in a late-breaking abstract (Abstract LBA8512). Johnson & Johnson, which is partnering with Genmab through its Janssen Biotech division to develop the drug, has told investors that the findings would support a new drug application in the United States and Europe this year, according to FirstWord Pharma. The FDA has designated daratumumab as a breakthrough therapy in this setting.
Pembrolizumab (Keytruda)—Findings about Merck’s PD-1 inhibitor will be reported across a broad range of tumor types in approximately a dozen abstracts, with notable results expected in advanced squamous cell carcinoma of the head and neck (LBA6008) and in the potential for the use of mismatch repair deficiency as a biomarker for response to the therapy in multiple tumor types (LBA100).
Avelumab—Updates on early clinical trial data will be provided for this PD-L1 inhibitor in metastatic or locally advanced solid tumors, recurrent ovarian cancer, and NSCLC (Abstracts 3044, 5509, and 8034). Merck Serona and Pfizer are collaborating on the development of this agent.
Afatinib (Gilotrif)—The overall survival analysis of the LUX-Lung 8 phase III trial of this EGFR inhibitor versus erlotinib (Tarceva) as second-line therapy for patients with advanced squamous cell carcinoma will be presented, along with data about patient-reported outcomes (Abstracts 8002 and 8100). The EGFR inhibitor, which Boehringer Ingelheim is developing, is approved for patients with metastatic NSCLC with EGFR exon 19 deletions or exon 21 mutations.
Trabectedin (Yondelis)—Findings from the phase III SAR-3007 trial comparing trabectedin with dacarbazine in patients with advanced liposarcoma or leiomyosarcoma will be presented (Abstract 10503). The FDA is evaluating trabectedin in this clinical setting under its priority review program, according to Janssen, which is developing the drug in the United States.