January 2016 Edition Vol.11, Issue 1

Phase 3 Hits and Misses of 2015

Phase 3 Hits and Misses of 2015

Based on OBR’s news archives, we’ve put together a recap of some of the more high profile phase 3 clinical trial results – both winners and losers – that were announced in 2015. Be advised that our list is by no means all inclusive, and is only meant to jog your memory as to what some of the highlighted late-stage trials were from the past year.  So read on.


1) In the pivotal KEYNOTE-010 phase 2/3 study, Merck’s anti-PD-1 (programmed death receptor-1) therapy Keytruda® (pembrolizumab) significantly improved overall survival (OS) compared with chemotherapy in patients with any level of PD-L1 expression, as defined by a tumor proportion score of 1% or more.  It was the first study of its kind to evaluate the potential of an immunotherapy compared with chemotherapy, based on prospective measurement of PD-L1 expression in patients with advanced non-small cell lung cancer (NSCLC). (Dec. 19, 2015)

2) In top-line results reported from the NEMO trial, patients with advanced NRAS-mutant melanoma treated with binimetinib (Array BioPharma) lived for a median of 2.8 months before their disease worsened, compared with 1.5 months for patients treated with dacarbazine. The trial met its primary endpoint of improving progression-free survival (PFS). (Dec. 16, 2015)

3) In the BELLE-2 trial, women with metastatic hormone receptor-positive breast cancer resistant to hormone therapy who had mutated PIK3CA detected in their blood benefited from a combination of the PI3K inhibitor buparlisib and fulvestrant. Women had 7 months of PFS in the combination arm compared with only 3.2 months for those receiving fulvestrant plus a placebo. (SABCS, Dec. 11, 2015)

4) In the RAY trial of mantle cell lymphoma (MCL), Imbruvica significantly improved PFS versus Pfizer’s Torisel® (temsirolimus).  Janssen’s therapy was associated with a 57% reduction in the risk of disease progression or death with a median follow-up of 20 months. (ASH, Dec. 8, 2015)

5) In STUDY 115, conducted with patients with previously treated chronic lymphocytic leukemia (CLL), a triplet of Gilead’s Zydelig® (idelalisib) in combination with bendamustine and rituximab (BR) proved superior to bendamustine/rituximab alone, increasing both PFS and OS, with a 67% reduction in the risk of progression or death and a 45% reduction in death.  The trial was stopped early due to “overwhelming efficacy.” (ASH, Dec. 8, 2015)

6) Results from the TOURMALINE-MM1 trial in relapsed and/or refractory multiple myeloma showed that an oral triplet combination of Takeda’s Ninlaro® (ixazomib), lenalidomide, and dexamethasone significantly improved PFS, compared with the doublet of lenalidomide and dexamethasone. Median PFS was 20.6 months with the triplet versus 14.7 months in the control group. Ninlaro, the first available oral proteasome inhibitor, offered patients with multiple myeloma the option of taking an all-oral treatment regimen. (ASH, Dec. 7, 2015)

7) The PROTECT 2 study of Novartis’s pegfilgrastim, a biosimilar of Amgen’s Neulasta® (pegfilgrastim)‎, met the trial’s primary endpoints and demonstrated similar safety and efficacy to the original product for the prevention of neutropenia in patients with breast cancer. (Dec. 7, 2015)

8) The RESONATE study showed that some elderly patients with treatment-naive chronic lymphocytic leukemia (CLL) fared much better on Janssen’s Imbruvica® (ibrutinib) compared with those who were given standard chemotherapy (chlorambucil). At 24 months, patients taking ibrutinib achieved a 98% OS rate, a key secondary endpoint of the trial, versus 85% for chlorambucil. Ibrutinib also significantly prolonged PFS, reducing the risk of progression or death by 84%, the primary endpoint of the trial, versus chlorambucil. (ASH, Dec. 6, 2015)

9) In the RATIFY (CALGB 10603) study, Novartis’s experimental drug PKC412 (midostaurin), added to standard chemotherapy, became the first targeted treatment to improve survival for a high-risk, genetically defined subgroup of patients – OS improved by 23% for patients with FLT3-mutated acute myeloid leukemia (AML). (ASH, Dec. 6, 2015)

10) In the coBRIM trial, Roche/Exelixis’s Cotellic (cobimetinib) used in combination with vemurafenib helped people with previously untreated BRAF V600 mutation-positive advanced melanoma live significantly longer compared with vemurafenib alone. The median OS was 22.3 months for the combination versus 17.4 months for vemurafenib alone, or a 30% reduction in the rate of death for the combination compared with vemurafenib alone. (Nov. 21, 2015)

11) Novartis announced results of the RADIANT-4 study showing that Afinitor® (everolimus) reduced the risk of disease progression by 52% versus placebo in patients with advanced, progressive, nonfunctional neuroendocrine tumors (NET) of gastrointestinal (GI) or lung origin. (ECC, Sept. 27, 2015)

12) Treatment with Exelixis’s Cometriq® (cabozantinib) reduced the rate of disease progression or death (progression free survival) by 42% compared with Afinitor in the METEOR trial, which compared cabozantinib with everolimus in patients with advanced clear-cell renal cell carcinoma (RCC) previously treated with at least one VEGF-targeted drug.  (ECC, Sept. 26, 2015; Jul. 20, 2015)

13) The results from the CHECKMATE -025 trial marked the first time that an immuno-oncology drug, in this case Bristol-Myers Squibb's Opdivo® (nivolumab), demonstrated the ability to help patients live longer. Patients with previously treated advanced renal cell carcinoma (RCC) taking Opdivo had a median OS of 25 months, or more than two years, as compared with 19.6 months for those on everolimus, a current standard of care for kidney cancer. The trial was stopped early since it met its endpoint.  (ECC, Sept. 25, 2015; Jul. 20, 2015)

14) Amgen’s investigational virus-based immunotherapy, Imlygic (talimogene laherparepvec), significantly increased the durable response rate in patients with metastatic melanoma compared with granulocyte-macrophage colony-stimulating factor (GM-CSF) in the OPTiM trial.  The trial was the first for an oncolytic virus to show a benefit in patients with cancer. (Jul. 21, 2015)

15) Data from the COMPLEMENT 2 study in relapsed chronic lymphocytic leukemia showed that a combination of Novartis’s Arzerra® (ofatumumab), fludarabine, and cyclophosphamide boosted PFS by 54% compared with therapy with the latter two drugs alone (28.9 months versus 18.8 months, respectively). (EHA, Jun. 18, 2015) 

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