Grant Announcement for Study Using NK Cells to Treat Ovarian Cancer at Dana-Farber Cancer Institute
Ovarian Cancer (EOC) is the 5th leading cause of cancer deaths in women, and most are diagnosed when disease is advanced. For these women, the 5-year survival rate is under 30%. Initial standard therapy is comprised of platinum-based chemotherapy and surgery. Most patients relapse soon after treatment with tumors that are resistant to existing therapies, so novel treatments are urgently needed. PHASE ONE’s most recent grant funds a new trial that specifically examines a new regimen comprised of a cellular therapy and two novel agents used in combination, for treatment of relapsed and drug-resistant ovarian cancer.
Natural Killer (NK) cells are a type of immune cell that can recognize and kill cancer cells if present in sufficient numbers and properly stimulated. NK cells have shown great promise in preclinical experiments, but their success in killing tumor cells in human subjects is hampered by short-lived existence. NK cells can be made more persistent and potent by pre-activation with interleukins to form cytokine induced memory-like NK cells (CIML NK cells). Additional agents can then be used to enhance their activity and durability in humans.
This study, led by Dr. Rebecca Porter at Dana-Farber Cancer Institute, examines a novel combination of three synergistic agents: a cellular agent with in vivo durability (pre-activated autologous CIML NK cells), an immunologic agent to enhance biological activity of those NK cells (IL-15 super-agonist), and a novel PD-1 Inhibitor agent to confer greater longevity for therapeutic NK cells (Spartalizumab). IL-15 super-agonists have already been proven to enhance NK cell cytotoxicity (effectiveness in destroying cancer cells) in in vivo studies on ovarian cancer. PD-1 inhibitors have shown efficacy in ex vivo models of ovarian cancer and in current in vivo clinical trials for therapy of other tumor types. The three agents used in this trial show promising results in other cancer types, but until now, they have remained unexplored in ovarian cancer and the combination is novel.
Dr. Porter says, “While immune-based therapies have been revolutionizing the treatment of some cancers, standard immunotherapies have not been beneficial yet for patients with platinum resistant ovarian cancer - a disease that has few effective treatment options – and novel combination strategies are critically needed.”
The trial will initially determine safety and tolerability of the regimen of these three agents. Ultimately, it will measure objective response rates through progression-free survival and duration of response in patients with platinum-resistant recurrent high-grade ovarian carcinoma. Dr. Porter’s Phase Ib trial is the critical first step in translating this novel use of these three synergistic agents to treatment of recurrent ovarian cancer, with the goal of improving outcomes in a population with very limited treatment options.
Dr. Porter is looking forward to getting this trial underway, saying “We are excited to test the safety and initial activity of NK cells combined with immunotherapy in women with recurrent platinum resistant ovarian cancer, and grateful for the support from PHASE ONE which is making this innovative clinical trial possible.”