Stay Up
to Date
Stay Up
to Date
Breaking News,
Updates, & More
Breaking News,
Updates, & More
Click Here to
Subscribe
Click Here to
Subscribe

Adding Indoximod to Pembrolizumab Boosts Immune Response in Melanoma

TOP - August 2017, Vol 10, No 3 - Melanoma, Immunotherapy
Phoebe Starr

Washington, DC—Adding the investigational drug indoximod, an indoleamine 2,3-dioxygenase (IDO) pathway inhibitor, to the checkpoint inhibitor pembrolizumab led to higher response rates in patients with advanced melanoma than what is reported with pembrolizumab monotherapy, said lead investigator Yousef Zakharia, MD, Clinical Assistant Professor of Internal Medicine, Division of Hema­tology, Oncology and Blood and Marrow Transplantation, University of Iowa, Iowa City, at the 2017 American Association for Cancer Research meeting.

The IDO pathway is a key player in cancerogenesis. Dr Zakharia presented the results of an interim analysis of a phase 2 clinical trial.

Previously, in the pivotal phase 3 KEYNOTE-006 clinical trial, the overall response rate (ORR) to first-line pembroliz­umab in advanced melanoma was 33%. By contrast, the ORR was 52% in the phase 2 study with the novel combination of indoximod plus pembrolizumab.

“These results justify moving the combination of indoximod plus pembrolizumab forward to a phase 3 trial,” said Dr Zakharia. “Several IDO inhibitors in development are being studied in multiple solid tumors and hematologic malignancies,” he said.

Study Details

The phase 2, open-label, single-arm study enrolled 102 patients with stage III (13%) or stage IV (87%) advanced, unresectable melanoma who received indoximod plus pembrolizu­mab until disease progression. Of these patients, 40 (87%) had cutaneous melanoma, 9 (15%) had ocular melanoma (a type of melanoma that has very poor response to any therapy), and 11 (18%) had nonocular melanoma.

Patients could switch to a second checkpoint inhibitor (primarily ipilimumab) at disease progression and continue receiving indoximod.

Of the 60 patients who were evaluable for response, 31 (52%) achieved ORR; 6 achieved a complete response (CR) and 25 achieved a partial response. Of the 51 patients with cutaneous or nonocular melanoma, 30 (59%) achieved ORR; 6 achieved a CR and 24 achieved a partial response. The disease control rate (ie, response plus stable disease) was 73% in the overall patient population and 80% in the group with cutaneous or nonocular melanoma.

“This is the largest publicly available data set on IDO inhibitors plus checkpoint inhibitors,” Dr Zakharia noted.

In this study, as in other studies of different therapies, patients with ocular melanoma had a poor response to the combination therapy.

“We had impressive responses in nonocular melanoma, with many patients near CR,” said Dr Zakharia. The majority of the responses occurred within the first months of treatment.

The indoximod combination was well-tolerated. The majority of adverse events were as expected, with few grade 3 adverse events and no grade 4 adverse events. Serious adverse events potentially related to indoximod therapy were reported in 4 patients (ie, grade 3 arthritis, gastritis, and hearing impairment; and grade 2 interstitial nephritis), and 3 of these patients discontinued treatment. No treatment-related deaths were reported.

Priming the Immune Response

Dr Zakharia and colleagues were not able to identify biomarkers for response in the patients studied to date, although there was a suggestion for an improved response with elevated PD ligand 1 (PD-L1) expression.

“One could arguably say that the combination appears to get a better response with higher PD-L1 expression, but this needs to be interpreted with caution,” he said.

The press conference moderator, Louis M. Weiner, MD, Director, Georgetown Lombardi Comprehensive Cancer Center, Washington, DC, called these results “exciting,” and, if validated, “would represent a real advance.”

“It’s too soon to tell, but the approach of priming the immune response with novel strategies looks promising,” said Dr Weiner. “It will be a vigorous competition among ways to manipulate checkpoint inhibitors, but we don’t know who will win,” he added.

Related Items
First Positive Showing for Mesothelin-Directed CAR T-Cell Therapy in Solid Tumors
Wayne Kuznar
TON - June 2019, Vol 12, No 3 published on June 17, 2019 in Immunotherapy
Osimertinib plus Savolitinib Promising for Non–Small-Cell Lung Cancer with MET-Driven Resistance
Phoebe Starr
TON - June 2019, Vol 12, No 3 published on June 17, 2019 in Lung Cancer
High Tumor Mutation Burden Predictive Biomarker for Survival in Metastatic Non–Small-Cell Lung Cancer
Phoebe Starr
TON - June 2019, Vol 12, No 3 published on June 17, 2019 in Lung Cancer
Gilteritinib a New Standard of Care for Relapsed or Refractory AML with FLT3 Mutation
Phoebe Starr
TON - June 2019, Vol 12, No 3 published on June 17, 2019 in Leukemia
Infigratinib a Novel, Potent Selective TKI Targeting FGFR Fusions in Different Tumor Types
Phoebe Starr
TON - June 2019, Vol 12, No 3 published on June 17, 2019 in Emerging Therapies
Umbralisib Shows Encouraging Results in Relapsed or Refractory Marginal-Zone Lymphoma
Phoebe Starr
TON - June 2019, Vol 12, No 3 published on June 17, 2019 in Lymphoma
Braftovi (Encorafenib) plus Mektovi (Binimetinib) Third BRAF/MEK Inhibition Combination Approved for Metastatic Melanoma with BRAF Mutation
Lisa A. Raedler, PhD, RPh, Medical Writer
2019 Fourth Annual Oncology Guide to New FDA Approvals published on June 5, 2019 in FDA Approvals, Melanoma
Checkpoint Inhibition Consolidation Therapy Promising in High-Risk Hematologic Malignancies
Charles Bankhead
TON - April 2019, Vol 12, No 2 published on April 22, 2019 in Immunotherapy
Explosive Development of BCMA CAR T-Cell Therapies for Multiple Myeloma
Phoebe Starr
TON - April 2019, Vol 12, No 2 published on April 22, 2019 in Immunotherapy
5 mg Tamoxifen as Effective as 20 mg Daily in Early Localized Breast Cancer
Phoebe Starr
TON - February 2019, Vol 12, No 1 published on March 1, 2019 in Breast Cancer
Last modified: August 2, 2017