Early Data from Immunotherapy Studies in Advanced Cancer Patient Show Promise, Parker Institute Reports

Early Data from Immunotherapy Studies in Advanced Cancer Patient Show Promise, Parker Institute Reports
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clinical IO trials

Researchers at the Parker Institute for Cancer Immunotherapy have shown that the combination of Imfinzi (durvalumab) and tremelimumab, two immune checkpoint inhibitors, has a manageable safety profile and promising evidence of clinical activity in patients with advanced solid tumors.

In another study, researchers at this institute showed that adding the IDO-1 inhibitor epacadostat to Opdivo (nivolumab) also holds promise for advanced solid tumors, particularly in melanoma and squamous cell carcinoma of the head and neck.

These were two of the six selected abstracts from the Parker Institute, with results concerning the most recent advances in the area of immunotherapy, to be presented at the recent 2017 American Society Of Clinical Oncology (ASCO) Annual Meeting, that took place June 2-6 in Chicago.

The first presentation, titled “Phase 1 study to evaluate the safety and tolerability of MEDI4736 (durvalumab, DUR) + tremelimumab (TRE) in patients with advanced solid tumors,” covered data from an ongoing Phase 1 trial (NCT01975831) set to determine the safety and tolerability of the anti-PD-L1 Imfinzi (durvalumab) plus the CTLA-4 inhibitor tremelimumab in advanced solid tumors.

These antibodies target the key immune checkpoints that help tumor cells evade detection by the immune system.

In the trial, researchers have been testing the combination in patients with renal cell carcinoma, cervical cancer, colorectal cancer, non-triple-negative breast cancer, ovarian cancer, non-small cell lung cancer, or head and neck cancer.

The study’s primary goals are safety and tolerability, and identifying the maximum dose tolerated by patients. Secondary objectives include tumor response, deemed as the proportion of patients whose tumors shrank with the treatment, progression-free survival or the time to disease progression, and overall survival.

As of December 2016, 105 cancer patients were treated. The results showed that four patients experienced dose-limiting toxicities, which included diarrhea, colitis, abnormal liver function tests, and low levels of sodium in the blood.

The majority of treatment-related adverse effects were mild (grade 1 or 2). Grade 3 or higher  effects were reported in 12 patients and the majority included diarrhea/colitis (n = 5) and abnormal liver function tests (n = 4). There was one adverse effect of Grade 5, multi-organ failure.

Preliminary efficacy data also revealed a disease control rate (DCR), deemed as the proportion of patients experiencing at least disease stabilization, of 82% among renal cell carcinoma patients. For ovarian cancer and colorectal patients, the DCR was 48% and 46.2%, respectively.

Overall, these results suggest that the combination of Imfinzi plus tremelimumab “has a manageable safety profile, with preliminary evidence of clinical activity,” the researchers concluded. “These data support continued study of the combination therapy; the study is ongoing.”

In the second presentation, “Epacadostat plus nivolumab in patients with advanced solid tumors: Preliminary phase I/II results of ECHO-204,” researchers discussed another ongoing study, the Phase 1/2 ECHO-204 trial (NCT02327078), which is actively recruiting patients.

Here, researchers tested epacadostat, a first-in-class IDO1 inhibitor, combined with the PD-1 inhibitor Opdivo, in subjects with select advanced solid tumors and lymphomas. Eligible patients had melanoma, non-small cell lung cancer, colorectal cancer, head and neck squamous cell carcinoma, ovarian cancer, B-cell non-Hodgkin lymphoma (NHL), or Hodgkin lymphoma (HL).

In the Phase 1 part of the trial, patients received increasing doses of twice-daily epacadostat, combined with Opdivo (3 mg/kg every two weeks). In the Phase 2 part, patients received 100 mg or 300 mg epacadostat twice a day, together with Opdivo (240 mg every two weeks).

Results for overall safety and tolerability outcomes showed that the most common treatment-related adverse events were rash, fatigue, and nausea. Rash was the most common Grade 3 adverse event in patients treated with either 100 mg or 300 mg epacadostat.

Among the 23 patients with head and neck squamous cell carcinoma treated with 300 mg ecapadostat in the Phase 2 part, the disease control rate was 70%.

All eight melanoma patients treated with 100 mg ecapadostat had at least stable disease, and 75 percent had either a partial or a complete response. Treatment with 300 mg ecapadostat induced a lower disease control rate — 64%.

Eighteen ovarian cancer patients received 100 mg ecapadostat, and 11 received 300 mg ecapadostat. Overall response rate was 11% and 18%, and disease control rate was 28% and 36%, respectively.

Finally, the 25 colorectal cancer patients, all treated with 100 mg ecapadostat, showed an overall response rate of 4% and a disease control rate of only 24%.

The preliminary data showed that combining epacadostat with Opdivo “was generally well tolerated up to the maximum E 300-mg dose. [Phase 2] objective response rate/disease control rate outcomes are promising, particularly in [head and neck squamous cell carcinoma] and [melanoma patients],” the study concluded.

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