CESTAFOUR

CESTAFOUR

CESTAFOUR was a phase I/II clinical trial evaluating nadunolimab in combination with chemotherapy: first-line cisplatin and gemcitabine, third-line FOLFOX, and second- or third-line docetaxel.

The primary objective in the dose escalation phase of the study was to evaluate the safety of nadunolimab in combination with each of the three chemotherapy regimens. Secondary objectives included effect on biomarkers and anti-tumor activity.

The recruitment to CESTAFOUR was terminated prematurely due to strategic prioritization in October 2022 and did not proceed further into the expansion phase. A total of 36 patients were enrolled in the three treatment arms; nadunolimab combined with cisplatin and gemcitabine (14 patients, including 8 with bile duct cancer), FOLFOX (14 patients, including 5 with colon cancer) and docetaxel (8 patients, all with NSCLC).

The first arm of CESTAFOUR investigated the combination of gemcitabine/cisplatin in 14 patients and generated the strongest efficacy signal. In five severely pretreated (2-11 prior lines of therapy) patients with non-small cell lung cancer (NSCLC), 40% had a confirmed response according to RECIST 1.1 and progression-free survival (PFS) was measured at 10.2 months. The eight patients with bile duct cancer, predominantly second-line treatment, also showed promising results with a 13% confirmed response and PFS in 6.4 months.

The second arm of CESTAFOUR studied combination therapy with FOLFOX in 14 patients with 8 different cancers and varying treatment histories. Interestingly, three patients had a confirmed partial response, a fourth-line colorectal cancer, a first-line gastric cancer, and one who received third-line testicular cancer treatment. PFS in this heterogeneous patient group was 4.6 months.

The third arm of CESTAFOUR investigated combination with docetaxel and included eight, second- or third-line, patients with NSCLC. The protocol was designed to allow frequent dose reductions during the initial phase and therefore the efficacy results are not conclusive.

In line with data from the CANFOUR study, an association was observed in CESTAFOUR between higher doses of nadunolimab and lower incidence and later onset of CIPN, providing further support for nadunolimab's potential neuroprotective role.

Read more about CESTAFOUR on ClinicalTrials.gov (NCT05116891).