Combining Five Prime Therapeutics‘ investigational therapy cabiralizumab with Opdivo (nivolumab) — with and without chemotherapy — failed to halt disease progression in people with advanced pancreatic cancer, compared with standard chemotherapy, findings from a Phase 2 trial show.
“Pancreatic cancer is a difficult disease to treat, and unfortunately the combination of cabiralizumab and Opdivo with and without chemotherapy did not show any meaningful benefit over standard of care chemotherapy in this randomized, controlled Phase 2 trial,” Helen Collins, MD, Five Prime Therapeutics’ executive vice president and chief medical officer, said in a press release.
The company received this information from Bristol-Myers Squibb, the trial sponsor and owner of cabiralizumab’s development and commercialization rights since October 2015, under an exclusive worldwide license and collaboration agreement.
Cabiralizumab, formerly known as FPA008, is an antibody that blocks the activation of the colony-stimulating factor 1 receptor (CSF1R), found at the surface of immune cells known as tumor-associated macrophages (TAMs).
TAMs contribute to tumor progression by suppressing the ability of immune T-cells to kill cancer cells; high numbers of TAMs are often linked with poor prognosis.
Studies in animal models of several cancers showed that blocking CSF1R activity in TAMS reduced the number of TAMS in the tumor microenvironment, while promoting T-cell infiltration and anti-cancer responses.
Thus, combining cabiralizumab with other therapies that boost the immune system, such as the immunotherapy Opdivo (by Bristol-Myers Squibb), could potentially result in greater therapeutic benefits in cancer patients.
Preliminary data from a previous Phase 1a/1b trial (NCT02526017) assessing the safety and effectiveness of cabiralizumab plus Opdivo in a number of advanced cancers suggested durable clinical benefits in heavily treated pancreatic cancer patients.
Thus, an international Phase 2 clinical trial (NCT03336216), launched by Bristol-Myers Squibb, evaluated the effectiveness of the combination — with or without chemotherapy — in 160 people with locally advanced or metastatic pancreatic cancer that progressed during or after one line of chemotherapy.
Participants, recruited across 11 countries in America, Europe, and Asia, were randomly assigned to receive one of four treatment regimens.
In group A, patients received one of two standard of care chemotherapies — Onivyde (ironotecan liposome injection) plus gemcitabine or Abraxane (nab-paclitaxel) plus 5-fluorouracil and leucovorin — based on the investigator’s decision, while those in group B were treated with cabiralizumab plus Opdivo (combo therapy). Participants assigned to group C were given the combo therapy plus the Onivyde-based chemo and those in group D received the combo therapy with the Abraxane-based chemo.
The trial’s primary goal was to assess whether the combination therapy, with or without chemotherapy, could extend the time a patient lived without signs of disease progression (a measured called progression-free survival), compared with standard chemotherapy.
Secondary goals included the proportion of patients who achieved partial or complete responses to treatment, duration of responses, overall survival, safety measures, and clinically significant changes in disease biomarkers.
According to the recent announcement, the trial did not meet its primary goal, meaning that the cabiralizumab plus Opdivo combo did not improve progression-free survival in these patients. Bristol-Myers Squibb also reported that no new adverse events were observed in the trial.
“We are disappointed by this outcome and appreciate the participation of the investigators, staff, patients, caregivers, and our development partner who all contributed to the conduct and completion of this Phase 2 clinical trial,” said Collins.
Based on the data, Bristol-Myers Squibb will not pursue additional sponsored development of cabiralizumab, but will continue to support the evaluation of cabiralizumab in select, ongoing investigator-sponsored trials. The company also suggested that future development opportunities for cabiralizumab may be explored.
Cabiralizumab, alone or in combination with other therapies, is currently being evaluated in trials for selected advanced cancers, biliary tract cancer, pigmented villonodular synovitis, melanoma, non-small cell lung cancer, and renal cell carcinoma.
