EXCLUSIVE: Nektar Therapeutics, University of Texas MD Anderson Cancer Center Team Up on Phase 1/2 Trial of NKTR-214
Published: Jun 02, 2015
June 2, 2015
By Riley McDermid, BioSpace.com Breaking News Sr. Editor
Booming Nektar Therapeutics had some good news Tuesday, announcing it had inked a deal to team up with The University of Texas MD Anderson Cancer Center to initiate a Phase 1/2 clinical study to evaluate the its experimental drug NKTR-214, the company’s chief scientific officer told BioSpace .
"We’re excited to partner with MD Anderson on NKTR-214, which has the potential to become part of the next generation of cancer immunotherapies," Steve Doberstein, Nektar’s CSO, told BioSpace. “While the current crop of checkpoint inhibitors focus on inhibiting the regulation of the immune system, or releasing the brakes in order to allow one's own body to fight cancer, NKTR-214 is a next generation immuno-stimulatory drug that instead serves as an accelerator for the body's immune system to fight cancer.
That therapy is a CD122-biased cytokine designed to preferentially stimulate production of CD8-positive T cells, which are tumor killing cells found naturally in the body.
“It works by stimulating production and proliferation of the body's own CD8 positive tumor-killing T-cells within the tumor micro-environment itself,” said Doberstein. “So far, we’ve observed long and durable complete responses in preclinical tumor models in different types of cancer and we look forward to advancing it into human studies in different cancers as well.”
The partnership with MD Anderson will encompass a Phase 1/2 study to evaluate NKTR-214 in a variety of tumor types as a monotherapy and in combination with other therapies, including PD-1 pathway inhibitors. The company said it expects to initiate the first dose-escalation clinical study later this year, and that the two will conduct translational research to identify predictive biomarkers that can be used in the future development of NKTR-214.
The news is likely welcome: Nektar had mixed headlines in March after it reported solid topline results from its Phase III trial of its experimental breast cancer drug NKTR-102, saying it improved survival in patients studied by a little over two months. But the study missed its primary endpoint, throwing into doubt just how solid those results could be in the long term.
The drug showed an even higher rate of survival in a subgroup of patients whose breast cancer had spread to the brain and liver, improving survival by more than five months and two months, respectively. In 2012, the U.S. Food and Drug Administration (FDA) designated NKTR-102 as a Fast Track development program for the treatment of patients with locally recurrent or metastatic breast cancer progressing after treatment with anthracycline, taxane and capecitabine (ATC).
But based on a stratified log-rank analysis, the primary endpoint measuring the Hazard Ratio (HR) for survival in the NKTR-102 group compared to the active control arm was 0.87 with a p-value of 0.08, which did not achieve statistical significance. Because of some encouraging early data from prior trials, and the fast track designation, all eyes have been on Nektar.
The company (and a few Wall Street analysts) have remained wary, though some do feel the stock is undervalued.
“The Street remains skeptical regarding Nektar's ability to realize value from its Movantik partnership and its proprietary pipeline,” wrote Stephen Simpson over at Seeking Alpha on May 20. “BEACON results were disappointing, but there may yet be a path forward for NKTR-102 that can support multiple hundreds of millions of dollars in revenue. I estimate a fair value of $17.50, but Nektar seems like a classic "it's always something" stock that never gets much benefit of the doubt.”
March’s results were not disappointing in terms of progression and survival, but they did not come quite up to snuff.
Nektar’s BEACON study followed single-agent NKTR-102 in 852 patients with advanced breast cancer, comparing the dug to an active control arm comprised of a single chemotherapy agent of physician’s choice (TPC) in patients who were heavily pre-treated with a median of three prior therapies for metastatic disease.
Overall, NKTR-102 provided a 2.1 month improvement in median overall survival (OS) for 852 patients over TPC (12.4 months for patients receiving NKTR-102 compared to 10.3 months for patients receiving TPC).
In a pre-specified subgroup of patients with a history of brain metastases, NKTR-102 showed a statistically significant improvement of 5.2 months in median OS. The proportion of patients with brain metastases with 12-month survival was 44.4 percent in the NKTR-102 arm as compared to 19.4 percent in the control arm.
When treating liver cancer, NKTR-102 showed a statistically significant improvement of 2.6 months in median OS. In patients with baseline liver metastases, the proportion of patients with 12-month survival was 46.9 percent in the NKTR-102 arm as compared to 33.3 percent in the control arm.
Edith Perez, deputy director of the Mayo Clinic Cancer Center, and Javier Cortes, Director of the Breast Cancer Program at Vall d'Hebron University Hospital in Spain, served as co-principal investigators. BEACON enrolled 852 patients with advanced breast cancer.
“In BEACON, NKTR-102 provided a clinically meaningful benefit with a greater than two month survival advantage in these late-stage breast cancer patients, many who were refractory to existing therapies,” said Cortes. “NKTR-102 exhibited a lower rate of high grade adverse events including a reduced rate of neutropenia as compared to active control, which dramatically decreased the need for growth factor support in the NKTR-102 arm of the study.”
Secondary endpoints in the BEACON study included overall response rate (ORR) and progression-free survival (PFS), which did not achieve statistical significance in the study.
Will PfizerKline Become the Next Pharma Player?
The speculation surrounding a possible bid from Pfizer Inc. for struggling GlaxoSmithKline is heating up, after one closely-watched biotech analyst said in a note last week that Pfizer buying the company would “unlock access to its balance sheet and improve its tax situation.”
Gregg Gilbert, a biotech analyst at Deutsche Bank, wrote in a note to investors “Introducing PfizerKline” that he thinks a deal would be “materially accretive” for both companies. Gilbert estimated that a bid priced at $29.86 a share, via half stock and half cash, which would push up Pfizer’s earnings per share by 10 percent to 16 percent beginning in 2016.
“We believe that the company has a sense of urgency to create value by leveraging the power of its balance sheet to do needle-moving deals,” Gilbert wrote. “Since media reports in the past have pointed to the potential for a Pfizer/GSK combination, we are revisiting that theme.”
We want to know, dear readers, if you agree? Should Glaxo continue going it alone, or might Pfizer buy it and create one of the world’s largest pharma players in history?