Holden Comprehensive Cancer Center researcher Yousef Zakharia, MD, has presented promising data at a national meeting about combining a new investigational immunotherapy drug with an FDA-approved immunotherapy drug to treat patients with advanced melanoma.
The two drugs, indoximod and pembrolizumab, are both immunotherapy treatments which help activate the patient’s immune system to better fight cancer. Pembrolizumab (Keytruda) is an FDA-approved treatment for patients with advanced melanoma. In phase 3 clinical trial, this drug on its own produced partial or complete shrinking of tumors in 33 percent of patients involved in the trial.
“We set out to investigate whether we could improve upon this response rate by adding an inhibitor of the IDO pathway to pembrolizumab treatment,” says Zakharia, clinical assistant professor of internal medicine with University of Iowa Health Care.
Zakharia presented the preliminary findings at the American Association of Cancer Research annual meeting April 4 in Washington, D.C.
“We are excited to share interim results from the phase 2 portion of this clinical trial, because the data show that 52 percent of patients treated with a combination of pembrolizumab and the IDO-pathway inhibitor indoximod had a partial or complete response without significant added toxicities,” says Zakharia, who is also coleader of the early phase clinical trials program at Holden Comprehensive Cancer Center at the University of Iowa.
Furthermore, he notes, the current trial did not exclude patients with ocular melanoma, a more aggressive form of the cancer, which has been shown to be less responsive to available systemic treatment.
“Most comparable trials do not allow patients with ocular melanoma,” Zakharia says. “When the results are considered without the ocular melanoma patients (9 out of 60), the response rate in cutaneous and nonocular melanoma is higher 59 percent. These robust data are very promising, but we need to confirm the clinical benefit in a larger, randomized trial.”
Previously reported results from the phase 1b portion of the clinical trial showed that the combination of indoximod and another FDA-approved immune checkpoint inhibitor called ipilimumab (Yervoy) was well tolerated and caused no increase in toxicity compared with the immune checkpoint inhibitor used alone.
In the phase 2 portion of the clinical trial, patients received indoximod and an FDA-approved immune checkpoint inhibitor drug of the treating physician’s choice, either pembrolizumab, nivolumab (Opdivo) or ipilimumab. Most patients received indoximod (1200 mg orally twice every day) with pembrolizumab, which was infused at the standard dose of 3 mg/kg every 21 days.
The new data being reported were obtained with a January 2017 cutoff data. After a median follow up of 10.5 months, six of 60 patients had a complete response and 25 had a partial response, giving an overall response rate of 52 percent. The most common adverse events were fatigue, diarrhea, and nausea.
“The trial is still accruing patients and we are continuing to monitor all of the patients enrolled so far,” Zakharia says. “This interim analysis represents the largest reported number of melanoma patients treated with the combination of an IDO-pathway inhibitor and standard checkpoint inhibitors to date.”
According to Zakharia, the main limitation of the study is that the clinical trial had no control arm, which means that a large-scale, placebo-controlled randomized clinical is needed to confirm the current results.
This study was funded by NewLink Genetics. Zakharia has received scientific conference travel support from NewLink Genetics.
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