A Phase II basket study of the oral selective pan-FGFR inhibitor Debio 1347 in subjects with solid tumors harboring a fusion of FGFR1, FGFR2 or FGFR3
- Conditions
- Solid Tumorscancer
- Registration Number
- NL-OMON48084
- Lead Sponsor
- Debiopharm
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 2
1. Written informed consent given according to ICH/GCP guidelines and local
regulations.
2. Cytologically or histologically confirmed advanced solid tumor.
3. Radiographic progression on prior systemic therapy; prior localized therapy
(i.e., radiation, ablation, embolization) is allowed provided radiographic
progression out-of-field or in the treatment field is shown.
4. Male or female *18 years of age.
5. Locally-advanced (unresectable) or metastatic disease harboring an FGFR1-3
gene fusion/rearrangement potentially leading to a functional FGFR aberrant
protein, identified through local and/or central molecular assay.
6. At least one prior standard therapy appropriate for tumor type and stage of
disease. In particular:
a. Biliary tract cancer subjects must have progressed on/after
gemcitabine-based chemotherapy (including subjects who progressed within 6
months of gemtabicine-based adjuvant chemotherapy).
Subjects can have received additional chemotherapy after documented intolerance
to gemcitabine.
b. Urothelial cancer subjects must have progressed on/after cisplatinbased or
carboplatinbased chemotherapy either given for advanced disease or within 12
months from completion if given as neoadjuvant or adjuvant therapy and
anti-PD1/PDL1 therapy (unless not available,
contraindicated for some reasons or refused by the patient).
c. NSCLC subjects must have progressed on chemotherapy and anti PD1/PDL1
therapy (unless contraindicated for some reasons). Subjects with known EGFR
mutations, ALK rearrangement or BRAF V600E mutation must have received the
relevant target therapy (unless not
available).
d. For all other tumor types, subjects must have progressed on/after
appropriate SOC therapy (evidence-based level 1). Subjects who harbor genomic
aberrations for which approved target therapy is available must have received
such therapy. HER2+ or ER/PR+ breast cancer subjects
should have received at least one line of HER2-targeted or ER-targeted,
respectively.
7. Measurable disease according to RECIST criteria version 1.1.
For further Inclusion Criteria please refer to the Protocol.
1. History of hypersensitivity to any of the excipients in the Debio 1347
formulation.
2. Prior treatment with a FGFR1-3 selective inhibitor.
3. History and/or current evidence of ectopic mineralization/calcification,
including but not limited to soft tissue, kidneys, intestine, myocardia, or
lung, excepting calcified lymph nodes, lung nodules and asymptomatic vascular
or cartilage/tendon calcifications.
4. Current evidence of clinically significant corneal or retinal disorder
confirmed by ophthalmologic examination.
5. Chemotherapy or radiotherapy within 2 weeks prior to initial dosing with
Debio 1347.
6. Administration of any investigational agent within 2 weeks prior to initial
dosing with Debio 1347 (3 weeks for immune checkpoint inhibitors).
7. Surgery requiring general anesthesia, except diagnostic biopsy or local
procedure, within 3 weeks prior to initial dosing with Debio 1347 and/or if the
subject has not fully recovered from the surgery.
8. Grade > 1 NCI-CTCAE v5.0 AEs or toxicities from previous treatments except:
a. Albumin (* 2.5 g/dL is allowed).
b. AST and ALT in subjects with liver metastases.
c. ALP in subjects with bone metastases .
d. Any grade of alopecia is allowed.
e. Other Grade 1-2 clinically insignificant laboratory abnormalities are
allowed.
For further Exclusion Criteria please refer to the Protocol.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>ORR (defined as the proportion of subjects with a BOR of partial or complete<br /><br>response) as centrally measured by RECIST 1.1 criteria.</p><br>
- Secondary Outcome Measures
Name Time Method <p>1. DoR (defined as the time from the date of the initial partial or complete<br /><br>response to date of the first documented progression or death due to any cause).<br /><br>2. DCR (defined as the proportion of subjects with a BOR of CR or PR or SD).<br /><br>3. PFS (defined as the time from the start date of treatment to date of the<br /><br>first documented progression or death due to any cause).<br /><br>4. OS (defined as the time from the start date of treatment to date of death<br /><br>due to any cause).<br /><br>5. Proportion of subjects with TEAEs assessed by NCI-CTCAE v5.0 and SAEs.<br /><br>6. Debio 1347 plasma exposure (Ctrough, AUC and any other PK parameters as<br /><br>deemed appropriate) and relationships with efficacy and safety endpoints; Debio<br /><br>1347 plasma concentration (C)-QTcF relationship based on ECG and PK matching<br /><br>time-points.</p><br>