CANFOUR

CANFOUR

CANFOUR, the first clinical trial for nadunolimab (CAN04), is a combined phase I/IIa study. In the initial phase, the aim was to study the safety of CAN04 to determine an appropriate dose for the subsequent phase which evaluates the efficacy and safety of CAN04 in combination with chemotherapy.

Read more about CANFOUR on ClinicalTrials.gov (NCT03267316).

Phase I: Dose escalation and safety evaluation - Completed

• Included 22 patients with pancreatic cancer (PDAC), non-small cell lung cancer (NSCLC) and colorectal cancer.
• The results showed that CAN04 has a high level of safety, and positive effects on biomarkers linked to cancer were observed:
  • Good safety profile up to 10 mg/kg
  • Decrease of the biomarkers IL-6 and CRP
  • Stable disease in 43% of patients
• The results from the phase I part were published in British Journal of Cancer in December 2021 and can be found here.

Phase IIa: Evaluation of therapeutic effects - Ongoing; recruitment completed

• Evaluates CAN04 in combination with chemotherapy in patients with PDAC (first line with gemcitabine/nab-paclitaxel), NSCLC (first or second line with cisplatin/gemcitabine) or non-squamous NSCLC (first or second line with carboplatin/pemetrexed).
• A total of 76 PDAC patients were enrolled (36 in a primary cohort, 40 in an expansion cohort).
• A total of 43 NSCLC patients were enrolled (33 with the cisplatin/gemcitabine combination, 10 with the carboplatin/pemetrexed combination).

Positive interim phase IIa data for combination therapy in PDAC patients - Presented at AACR 2023

• The overall survival of the 73 PDAC patients treated with CAN04 and gemcitabine/nab-paclitaxel was 12.9 months, well above that achieved by chemotherapy alone [1].
• Even stronger efficacy was observed in patients with high tumor levels of IL1RAP, the target of CAN04, including significantly prolonged median overall survival, compared to patients with low IL1RAP levels (14.2 vs 10.6 months; p=0.017).

Tumor responses according to iRECIST (left); overall survival for the 46 PDAC patients from which tumor biopsies were collected and patients subgrouped based on tumor levels of IL1RAP (high, n=27; low, n=19) (right).

Efficacy parameters for the total PDAC patient cohort, the two IL1RAP level subgroups, and historical control data.

• The safety profile of the gemcitabine/nab-paclitaxel combination was similar to that of chemotherapy alone:
  • Neutropenia and febrile neutropenia were more frequent than expected from the chemotherapy alone primarily during the first cycle.
  • With G-CSF prophylaxis, only 14% of patients developed grade 3-4 neutropenia, compared to 78% without prophylactic G-CSF.
  • The incidence of grade 3-4 neuropathy was only 1%, compared to 17% previously reported for chemotherapy alone [1].

Positive interim phase IIa data for combination therapy in NSCLC patients - Presented at ASCO 2023

• The 30 NSCLC patients treated with CAN04 and cisplatin/gemcitabine had an ORR of 53%, with median overall survival and progression-free survival of 13.7 months and 7.0 months, respectively. These data are stronger than historical data for chemotherapy only [2-4].
• The strongest clinical benefit was observed in the 16 patients with non-squamous NSCLC, including 15.9 months median overall survival.

Tumor responses according to RECIST (left); overall survival (OS) and progression-free survival (PFS) for the total 30 NSCLC patients (right).

Efficacy parameters for the total NSCLC patients, the non-squamous subgroup, and historical control data.

• Among the 16 non-squamous NSCLC patients, two had complete response; both were previously progressed on Keytruda® and had no detectable PD-L1 on their tumor cells.
• One of the complete responses was achieved after almost 9 months of CAN04 monotherapy, given after termination of chemotherapy, while the other had a rapid response to the combination therapy that has been maintained for over 3 years.

• The safety profile of the combination was acceptable and readily managed:
  
  • Neutropenia and febrile neutropenia were more frequent primarily during the first cycle compared to historical data for chemotherapy alone [2].
    
  • Only 33% of patients treated prophylactically with G-CSF developed grade 3-4 neutropenia, a level similar to chemotherapy alone, compared to 71% without prophylactic G-CSF.

References

[1] von Hoff et al, N Engl J Med 2013; 369:1691-1703

[2] Schiller et al, N Engl J Med 2002; 346:92–98

[3] Scagliotti et al, J Clin Oncol 2008; 26:3543–3551

[4] Gandhi et al, N Engl J Med 2018; 378:2078-2092