Lauren M. Green, OncLive

Study assesses the safety and tolerability of TH-302 in combination with dexamethasone.

The addition of the investigational hypoxia-targeted drug TH-302 to dexamethasone has demonstrated beneficial activity and a manageable adverse event profile in the treatment of patients with relapsed/refractory multiple myeloma, according to findings of a phase I/II multicenter study presented at the 2014 ASCO Annual Meeting.

TH-302 is activated under tumor hypoxic conditions, a hallmark of many cancers including hematologic malignancies, representing a new therapeutic target for multiple myeloma where the bone marrow of patients has been shown in some cases to be severely devoid of oxygen.

The agent is a member of the class of alkylating drugs with “a half-century, proven track record in multiple myeloma,” noted lead trial investigator Jacob Laubach, MD, but “what’s unique about TH-302 is that it is essentially a smart alkylator, in this case targeting cells that reside in a hypoxic environment.”

Laubach is clinical director of the Jerome Lipper Multiple Myeloma Center at the Dana Farber Cancer Institute. He spoke with OncLive following an ASCO poster highlights session where the trial’s phase I dose-escalation and ongoing phase II dose-expansion findings were presented. Patients with relapsed/refractory myeloma and an ECOG performance status of 0-2 who had received at least two prior therapies were eligible for the study.

Findings presented at ASCO were from 24 patients with a median age of 62.5 years who had received a median of 6.5 prior therapies (range: 3-13). Four of the 24 patients remained in treatment at the May 19 cutoff. The study’s primary objectives were to assess the safety and tolerability of TH-302 in combination with dexamethasone, identify any dose-limiting toxicities, and determine the maximum tolerated dose (MTD). 

A dose of 340 mg/m2 emerged from the study as the MTD for TH-302, which is administered intravenously biweekly in combination with 40 mg of oral dexamethasone. The clinical benefit rate (based on partial response [PR] + minimal response [MR]) was 31%, with three patients experiencing PR and two, MR. Objective responses were also observed in patients who had failed multiple immunomodulatory therapies including pomalidomide or multiple proteasome inhibitor therapies, including carfilzomib. 

Click here to read the full article on OncLive and for full coverage of ASCO 2014

Articles

â€˜Smart' Alkylator TH-302 Shows Clinical Benefit in Early Multiple Myeloma Trial 

The Affordable Care Act will expand coverage and may open the door to elevated roles for pharmacists, former Health and Human Services Secretary Donna Shalala argued in a speech at the Miami Breast Cancer Conference.

Physicians wondering how the Affordable Care Act (ACA) will impact their practices heard a robust defense of the new law from Donna E. Shalala, PhD, on Saturday, who contended the law’s essential focus on expanding coverage for all Americans will be both a source of new energy and new funding for America’s health care system, while also offering some longer-term approaches for grappling with the rising costs of care.

Acknowledging that the debate over the ACA, often referred to as “Obamacare,” has been a contentious one, Shalala, who for eight years served as President Bill Clinton’s Secretary of Health and Human Services and is now president and a professor of political science at the University of Miami, noted that such debates over health care have been going on since the 1930s, when President Franklin D. Roosevelt had hoped to include health care protections for the elderly in the Social Security Act.

It took another 30 years for Roosevelt’s vision to be realized when President Lyndon B. Johnson, whom Shalala described as a “master politician,” was able to push through the Medicare and Medicaid legislation. Shalala noted that just like today’s debate over the federal government’s role in health care, Johnson’s process was, “messy, too, but his was carried out in smoky backrooms”—and with a lot of arm-twisting. Getting the 1965 law passed wasn’t easy, either, and it was contingent on significant Medicaid dollars going to the South and meeting the American Medical Association’s insistence that physician participation be voluntary. To secure passage, Medicare also needed to be set up so that private insurance contractors would administer the program, a system that has been retained to this day.

Medicare is now firmly intertwined into the fabric of American life, said Shalala, and she stressed that the program does not just benefit the elderly. Middle-class workers and families depend on the financial security these benefits provide for themselves and their elderly family members: “If you or your employees had to go into the marketplace and buy health insurance for your elderly relative, you couldn’t do it,” she noted. Forty million Americans lack health insurance today, and that is the gap she said Obamacare is intended to bridge, stressing that most of these individuals are Americans who are working but often employed in multiple low-paying jobs that don’t offer health insurance or with firms that don’t provide it. Or, even if their employers do offer insurance, many workers’ salaries are too low to afford the premiums. “Under the new plan, it’s these working Americans who now have access to health insurance,” she said.

The law’s impact on slowing the growth in health care costs will be seen more in the longer term, said Shalala. “In essence, it’s a coverage program. We haven’t in a serious way gotten to the affordability issue; we’re nicking around the edges,” although she pointed out that increased investment in prevention and primary care would lead to more early diagnoses and fewer visits to the emergency department which are expected to yield cost benefits over time. “Charity care was being absorbed into the system,” she said, ratcheting up costs across the board. In addition, the law’s emphasis on coordinated health care delivery systems should provide patients with more seamless access to specialists and allow them to get to the doctor sooner.

The law also doesn’t settle the issue of drug pricing, nor solve the administrative burden insurance paperwork places on busy practices. “Those are later initiatives that both the insurance companies and the government have been working on,” she said. Tort reform also needs to be addressed, she said, although that is primarily an issue for the states. Rising health care costs also have been cutting into the ability of academic centers to invest in their research, she added. Another concern is whether there will be enough health care professionals to deliver care, as previously uninsured individuals start seeking it, those with pre-existing conditions are no longer excluded, and the number of older Americans needing medical care climbs due to demographic shifts. Here, Shalala would like to see the scope of practice expand to allow elevated roles for nurse practitioners, physicians’ assistants, and pharmacists, for example. “Let people work up to their training and not just to an artificial license,” she said.

What worried providers may not realize, Shalala emphasized, is that the ACA is going to provide a cushion of approximately $1 trillion in funding overall for the health care system during the transition, but “we’re going to do it without substantially changing the way we deliver care.”

“This law,” she said, “is a giant step,” but it’s the discussion over the next five years that will be more difficult, as the focus moves to organizing the health care system so that it’s more affordable. She said a lot of these decisions are going to be made at the practice level in such areas as better coordination of care and leveraging the skills of other health care professionals, challenging her audience: “You can either sit in the back or lead.”

Finally, she said that Americans themselves also need to take more responsibility for their health care through making healthier lifestyle choices and being more informed consumers on the spending side. “We have an American public that wants the best health care in the world, but they don’t want to pay for it,” she said

The Affordable Care Act will expand coverage and may open the door to elevated roles for pharmacists, former Health and Human Services Secretary Donna Shalala argued in a speech at the Miami Breast Cancer Conference. 

It's All About Coverage

Finally, she said that Americans themselves also need to take more responsibility for their health care through making healthier lifestyle choices and being more informed consumers on the spending side. “We have an American public that wants the best health care in the world, but they don’t want to pay for it,” she said.