Arndt Vogel, MD

Arndt Vogel, MD, the managing senior consultant and professor in the department of Gastroenterology, Hepatology, and Endocrinology, at the Hannover Medical School, discusses the study results of the IMMUTACE (NCT03572582) study in hepatocellular carcinoma (HCC).

Within the single-arm, open-label phase 2 IMMUTACE study, investigators examined the 

efficacy of the combination of nivolumab (Opdivo) plus transarterial chemoembolization (TACE)

as a first-line treatment option in 49 patients with multinodular, intermediate-stage HCC. Those enrolled were administered TACE along with 240 mg of nivolumab administered intravenously every 2 weeks after 2 to 3 days. TACE was then repeated after 8 weeks.

The primary end point of the trial was overall response rate (ORR) with secondary end points of progression-free survival (PFS), time to progression, overall survival (OS), duration of response, objective of response, time to failure of strategy, quality of life, and incidence of treatment-emergent adverse events.

At the early readout of the study, findings revealed that the primary end point of ORR was met with a rate of more than 50%. Results for PFS, OS, and the other secondary end points remain early. While secondary end point data has not yet been reached, Vogel explains that the signals look promising.

 I think this was an early readout. The study met its primary end point. We observed a very high overall response rate of more than 50%. PFS and overall survival is still early. Specifically, patients were allowed to continue nivolumab after the first progression.


 I think we have to wait for more major data in respect to the very important secondary end points like overall survival. Although I think the combination looks very promising in respect to maybe some synergistic, at least additive activity, I think it's a promising signal for the currently ongoing and phase 3 studies which compare TACE alone to TACE with various combinations.

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Arndt Vogel, MD, discusses the study results of the IMMUTACE study in hepatocellular carcinoma.


Findings of the IMMUTACE Trial in Hepatocellular Carcinoma 

Arndt Vogel, MD, managing senior consultant and professor in the Department of Gastroenterology, Hepatology, and Endocrinology at Hannover Medical School, discusses the IMMUTACE (NCT03572582) study investigating the efficacy of transarterial chemoembolization (TACE) with nivolumab (Opdivo) in patients with intermediate-stage hepatocellular carcinoma (HCC).

IMMUTACE is a phase 2 single-arm, open label study of TACE in combination with nivolumab. TACE is the most common first-line treatment for HCC, and nivolumab is an anti–PD-1 agent. The trial was designed to evaluate if the combination improved the effect of TACE on tumors. According to Vogel, TACE could target and damage tumors while priming the immune system to receive nivolumab more effectively.

In the study, 49 patients were administered TACE, and after 2 to 3 days, 240 mg of nivolumab was administered intravenously every 2 weeks. TACE was repeated after 8 weeks. The primary end point was overall response rate (ORR). The investigators were looking at whether the combination showed efficacy of over 55% ORR. Vogel explains that the patients were able to achieve an ORR of over 70%, reaching the primary end point.

These results are preliminary, and other secondary end points such as overall survival, have not yet been reached. The study will continue for a maximum of 42 months. While this is a single-arm study, other ongoing studies will compare TACE alone with various combinations, and more data will be collected in future phase 3 studies.

 We tried to combine basically the best of both treatment approaches, specifically in patients with liver-limited disease. The idea was to use TACE to get control of the tumor. Maybe also destroy the tumor a little bit, which should lead to an antigen release [and] could prime the immune system to the checkpoint inhibitor, which we applied after the first TACE. Patients were allowed to receive that second TACE when it was considered reasonable by the investigator and then nivolumab was continued. And the idea was really to combine immunotherapy with local therapies to get a better disease control.

Since this was a proof-of-concept study, we used ORR as a primary end point, and we assumed a response rate of more than 55% as clinically meaningful. In the end, we were able to achieve a response rate of over 70%, indicating that the study met it primary end point. Based on the data we have seen so far, I think it looks like a very promising combination which should be pursued in subsequent and also phase 3 studies.

Arndt Vogel, MD, discusses the goals of the IMMUTACE study investigating the efficacy of transarterial chemoembolization with nivolumab in patients with intermediate-stage hepatocellular carcinoma.

Arndt Vogel, MD | Authors

Articles

Findings of the IMMUTACE Trial in Hepatocellular Carcinoma

Goals for TACE and Immunotherapy Trial in Intermediate-Stage HCC