DUBLIN – Immunicum AB found itself at odds with its shareholders on the interpretation of top-line data for its immunostimulatory allogeneic dendritic cell (DC) therapy ilixadencel, which has completed a phase II trial in 88 patients with metastatic renal cell carcinoma (RCC).

The Stockholm, Sweden-based firm touted the outcome as a "positive" result, based on an 11% complete response rate (CRR) among 45 evaluable patients in the treatment arm – which comprised ilixadencel plus the tyrosine kinase inhibitor (TKI) Sutent (sunitinib) – versus a 4% CRR for 25 evaluable patients in the control arm, who received Sutent only.

Shares in the company (STOCKHOLM:IMMU) dropped by as much as 26% during early trading Thursday, however, as investors digested the available – though still incomplete – survival data.

There was no difference between either arms in progression-free survival (PFS), in 18-month survival (63% for the combo vs. 66% for the control treatment) or in time to progression. Overall survival data are not yet mature, but Immunicum's chief medical officer Peter Suenaert told BioWorld that the trial was, in any case, an exploratory study designed to pick up efficacy signals. "It has not been powered for 18-month survival, overall survival or any other survival endpoint," he said.

At the same time, the company is standing over the CRR result, as a statistical analysis indicated that this outcome had only a 0.2% probability of being a chance finding. "That's why we strongly believe this is a true finding," Suenaert said. The OS outcome is still anybody's guess, given the high level of survival in each study arm.

"When you see a certain level of response, in combination with duration of response, that can translate into survival," he said.

One recent precedent, Suenaert observed, was the phase III trial comparing the programmed cell death protein 1 (PD-1) inhibitor Opdivo (nivolumab) with everolimus, a mammalian target of rapamycin (mTor) inhibitor, in second-line metastatic RCC. There was no significant difference in terms of median PFS (4.6 months for nivolumab vs. 4.4 months for everolimus) yet there was a meaningful difference in median OS (25.0 months for nivolumab vs. 19.6 months for everolimus).

Immunicum received the data Monday and is still crunching through the numbers. For now, its main conclusion is that the safety and efficacy data warrant continued development of intratumorally administered ilixadencel, which is designed to heat up cold tumors by releasing cytokines associated with a T1 helper response, which in turn recruit immune effector cells, including natural killer cells and immature dendritic cells, to the site of the tumor, leading to the processing and immune presentation of tumor-associated antigens, including neo-antigens.

The company also recently reported partial responses in two of six patients with gastrointestinal stromal tumors who had progressed during second, third or fourth-line TKI therapy.

Given the therapy's mode of action, a combination of ilixadencel and an immune checkpoint inhibitor may have a stronger scientific rationale than that of the combination tested in the present study. Such a study got underway in February. The so-called Iliad trial is testing ilixadencel in combination with the PD-1 inhibitor Keytruda (pembrolizumab) in a phase Ib/II trial in 150 patients with head-and-neck cancer, non-small-cell lung cancer or gastric cancer. It will take several years to complete.

In the meantime, Immunicum plans to complete the follow-up and data analysis for the present study and then consult with regulators and evaluate the competitive landscape before deciding on a path forward. A key question will be to analyze those patients who experienced complete responses, to see if they share any common characteristics. A pivotal trial could then follow, Suenaert said.

Immunicum's stock regained some of the lost ground to end the day at SEK8.86 ($0.91), down 14% on its previous close.

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