46O - Preliminary results from a phase IA trial of selective FGFR1-3 inhibitor CPL304110 in patients with FGFR-deregulated advanced solid malignancies

Background

Deregulation of fibroblast growth factor receptors (FGFRs) is related to the initiation and progression of multiple cancers. CPL304110 is a new tyrosine kinase inhibitor of FGFR 1–3 administered orally in phase I clinical study, aimed to evaluate safety, tolerability, and determination of the recommended phase II dose (RP2D), the dose-response relationship for efficacy, and pharmacokinetics of CPL304110.

Methods

Patients with advanced solid malignancies, received escalating doses of CPL304110, ranging from 12.5mg to 100mg qd in cohorts 1-4 (patients without screening for the presence of FGFR aberrations) and 175mg qd or bid in cohorts 5-6 (patients with FGFR aberrations), on 28-day cycle during phase IA of the trial.

Results

Twenty-one patients were enrolled during phase IA. The most common treatment-related adverse events (AE) included anemia (19%), ocular toxicity (19%, at median time of 48 dosing days), and dry eye (14.3%). Only one patient (4.8%) experienced ≥grade 3 drug-related AE, and no patients experienced dose-limiting toxicity so far. Using computed tomography-based RECIST 1.1 performed at baseline and at 22-day of every even cycle intervals from the start of treatment, 3 patients achieved partial responses (squamous lung cancer, basal cell carcinoma, cholangiocarcinoma) and 11 others had stable disease as the best response. The objective response rate (ORR; 3 partial responses) for cohorts 1-6 was 14.3% however, referring to the group of patients with FGFR aberration (cohorts 5-6), the ORR was 37.5%. Preliminary results of the study suggest low potential for CPL304110 accumulation and linear pharmacokinetics, however, these results need to be confirmed by data from more patients.

Conclusions

The above early study observations suggest that CPL304110 administration is associated with acceptable toxicity and encouraging response rate in heavily pretreated patients with FGFR-aberrant advanced solid malignancies. The final selection of RP2D will take place after the end of phase IB.

Clinical trial identification

CPL304110, NCT04149691.

Editorial acknowledgement

Legal entity responsible for the study

Celon Pharma SA.

Funding

This study was supported within the “CELONKO” project (STRATEGMED2/266776/17/NCBR/2015), co-financed by the Polish National Center of Research and Development, and the pharmaceutical company CelonPharma S.A.

Disclosure

I. Lugowska: Financial Interests, Personal, Invited Speaker, The reports of clinical trials: Roche, BMS, Macrogenics, Amgen; Financial Interests, Institutional, Other, Research grants: Roche, Agenus; Financial Interests, Personal and Institutional, Invited Speaker: Agenus, Roche, BMS, Janssen, Astra, Incyte, Macrogenics, Checkpoint Inhibitors, Celon, Pfizer, MSD, Debio; Non-Financial Interests, Personal, Project Lead: MSCI; Non-Financial Interests, Personal, Advisory Role, Board Member: EORTC. K. Roszkowski: Financial Interests, Personal and Institutional, Principal Investigator: National Institute of Tuberculosis and Lung Diseases. R. Dziadziuszko: Financial Interests, Personal, Advisory Board: AstraZeneca, Roche, Foundation Medicine, Amgen, Bristol-Myers Squibb, MSD, Novartis, Pfizer. L. Bodnar: Financial Interests, Personal, Advisory Board: GSK, AstraZeneca; Financial Interests, Personal, Other, personal fees: AstraZeneca, Roche, GSK; Financial Interests, Personal, Other, research funding and support: AstraZeneca, Rochem Novartis, MSD, Lilly, OncoQuest, Regeneron, Pharmaceutical, Gilead, Amgen, Exelixis. Inc. D. Popiel, M.M. Skupinska, A. Judycka, P. Rudzki: Financial Interests, Personal, Full or part-time Employment: Celon Pharma. J. Pieczykolan: Financial Interests, Personal, Stocks/Shares: Celon Pharma. M. Wieczorek: Financial Interests, Personal, Ownership Interest: Celon Pharma. All other authors have declared no conflicts of interest.