Immuno-Oncology Treatments Finding Success with Combination Therapies
With oncology drugs clocking a disheartening 3.4% success rate, some good news in the field is always appreciated.
Bristol Myers Squibb combined approved Opdivo with anti-LAG-3 antibody relatlimab in RELATIVITY-047, a Phase II/III trial. The trial compared the combo to use of Opdivo alone in metastatic melanoma patients. The drug mashup met its primary goal for progression-free survival.
Opdivo was first approved in 2015 for melanoma patients. An anti-PD1 monoclonal antibody therapy, it rode the wave of immuno-oncology treatments hitting the market at the time. While cutting-edge, many patients didn’t respond or developed a resistance to these types of treatments along the way. Combination therapies have become the next answer to effectively targeting tumors.
“The results of this study suggest that targeting the LAG-3 pathway in combination with PD-1 inhibition may be a key strategy to enhance the immune response and help improve outcomes for these patients,” said Jonathan Cheng, senior vice president and head of oncology development for BMS.
Relatlimab binds to and inhibits LAG-3, releasing the brakes tumors have put on T-cells to avoid being attacked. With LAG-3 inhibited, the immune system is able to work as intended against the cancer. According to a previous interview, the response rate then triples in LAG-3 positive tumor cells.
BMS is also trialing Opdivo with four other compounds in the fight against melanoma tumors. This month the company also announced a collaboration with AVEO Oncology, testing the combination of Opdivo and AVEO’s Fotivda against IO relapsed renal cell carcinoma.
Follow-up for the secondary endpoint of the RELATIVITY-047 trial, overall survival, is ongoing. The combo was well-tolerated with no new safety signals reported in either trial arm.
Pfizer also had some good news on a real-world evaluation of its Ibrance therapy in combination with letrozole in women with HR+, HER2- metastatic breast cancer when compared with letrozole alone. Around the two-year mark, median progression-free survival was 20 months in patients with Ibrance plus letrozole, versus less than 12 months with letrozole alone.
The combination treatment showed a 42% reduction in the risk of progression and a 34% reduction in risk of death.
“Real-world evidence is woven into the fabric of how we innovate and advance care for patients with breast cancer, supporting our randomized clinical trials,” said Chris Boshoff, M.D., Ph.D., Chief Development Officer, Oncology, Pfizer Global Product Development. “With more than six years of patient experience, a positive benefit-risk profile, strong clinical data and robust real-world data, the totality of evidence solidifies the role of IBRANCE plus endocrine therapy as a treatment for patients with HR+, HER2- metastatic breast cancer.”
Ibrance is currently in a Phase III trial as an addition to patient’s current anti-HER2 therapy and endocrine therapy, versus patients with anti-HER2 therapy alone. The expectation is the addition of Ibrance will delay therapeutic resistance and prolong overall survival for metastatic breast cancer patients.