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PD-L1 targeted antibody induced tumor shrinkage in several cancer types
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The investigational drug MPDL3280A, an engineered PD-L1 targeted antibody, significantly improved tumor shrinkage rates in patients with locally advanced or metastatic solid tumors that progressed despite prior treatments, according to study results.
The PD-L1 protein acts as a disguise, hiding cancer cells from the immune system. However, when the MPDL3280A (Genentech) antibody attaches to this protein, the cancer cells are no longer hidden and the body is able to fight the cancer.
Compared with prior PD-L1 targets, this new antibody enhances the safety and efficacy of treatment in patients with cancer, according to researchers.
Results of a phase 1 expansion study were presented during a press conference that highlighted select research that will be presented during the ASCO Annual Meeting.
Roy S. Herbst, MD, PhD, Ensign professor of medicine at Yale Cancer Center and chief of medical oncology at Smilow Cancer Hospital at Yale-New Haven, and colleagues assessed the efficacy of MPDL3280A in 140 patients with previously treated disease. Treatment was administered intravenously every 3 weeks and response was assessed by CT scan every 6 weeks.
MPDL3280A appeared safe, with most patients reporting improvements in cancer-associated symptoms.
Tumor shrinkage was observed in 21% of patients with non–small cell lung cancer, melanoma, renal cell carcinoma, colorectal cancer and gastric cancer. Therapy responses were still ongoing in 26 patients.
Herbst and colleagues then used a diagnostic test to assess the archived tumor tissue of 103 patients. Tumor shrinkage occurred in 36% of PD-L1–positive tumors and in 13% of PD-L1–negative tumors. However, the researchers said this test is still evolving; therefore, a negative result may mean a tumor has less PD-L1 than the test is able to detect.
“This drug is generally well tolerated, with no significant side effects,” Herbst said during the press conference. “The tumor PD-L1 expression appears to be associated with response to the agent, and further studies of monotherapy and other combination studies are planned.”
For more information:
Herbst RS. Abstract #3000. Scheduled for presentation at: ASCO Annual Meeting; May 31-June 4, 2013; Chicago.
Disclosure: The research was supported by Genentech.
Perspective
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Alex A. Adjei, MD, PhD
For decades, immunologists have tried to inhibit mechanisms of immune escape, which allows cancer cells to avoid killing by the host’s immune surveillance system, including cytotoxic T-cells. Anti-PD-L1 antibodies block a protein on cancer cells thought to be involved in immune escape, leading to the cells being susceptible to attack by the host’s defenses. These agents are broadly active and promise to lead a new era of immunotherapy.
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Clifford A. Hudis, MD
This is the first presentation of phase 1 data for this investigational drug. Clear indications of activity were seen in patients with non–small cell lung cancer and melanoma, and also importantly in patients who had tumors that tested positive for the PD-L1 marker. This suggests that, in the near future, we'll be able to develop a biomarker that identifies tumors that are more responsive to this particular approach. This is the beginning of an exciting new chapter in the treatment of cancer.
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