ASCO Highlights Include Phase III Findings in Multiple Tumor Types

Anita T. Shaffer @Shaffer1
Published: Wednesday, May 27, 2015

  • 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).
  • Pemetrexed, which Eli Lilly developed, already is approved in several settings in locally advanced or metastatic nonsquamous NSCLC, and the PROCLAIM trial will shed light on whether it offers clinical benefits over standard therapeutic choices.
  • 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.

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