Advanced or metastatic solid tumors (excluding lymphoma) MedDRA version: 21.1 Level: LLT Classification code 10065252 Term: Solid tumor System Organ Class: 100000004864
Conditions
Sponsors
PIERRE FABRE MEDICAMENT
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female subjects age = 18 years 2. Subjects with histologically or cytologically confirmed advanced or metastatic solid tumors (excluding lymphoma), unresponsive to standard treatment or for whom no standard treatment is available or appropriate i. In Cohort A1: Preferentially squamous non-small cell lung cancer, larynx carcinoma, ER positive breast cancer and soft tissue sarcomas ii. In Cohort A2 (inclusion criteria 37b): i. squamous Non-Small Cell Lung Cancer, squamous Head and Neck Carcinoma and Breast cancer (hormone receptor-positive, HER2-negative). ii. Others advanced solid tumor types with documented overexpression or genomic amplification of IGF-1R or that are deemed by the investigator to have a high probability of overexpressing IGF-1R. iii. In cohort A3 (inclusion criteria 2b): i. Subjects with histologically confirmed advanced or metastatic breast cancer ER+ HER2 negative ii. Prior treatment in the metastatic setting with a. CDK4/6 inhibitors b. At least one hormonal therapy c. One line of chemotherapy 3. Formalin-fixed paraffin-embedded (FFPE) archived tumor tissue block or representative slides for retrospective assessment of IGF-1R status after inclusion in the study i. In cohort A3 (inclusion criteria 3c): Evidence of IGF-1R expression evaluated centrally on a tumor biopsy obtained either at baseline or within 6 months prior to study entry defined as =50% of tumor cells showing high membranous IGF-1R expression scored 3+ by IHC. 4. ECOG performance status 0 or 1 5. Adequate bone marrow at screening i. Absolute neutrophil count (ANC) =1,500/mm3. ii. Platelet count =150,000/mm3. iii. Hemoglobin = 9 g/dL (6.2 mmol/L) Note: Any blood product transfusion is prohibited within 2 weeks before the first study treatment administration (Cohorts A1, and A2 only). 6. Adequate liver function at screening i. Total Bilirubin = 1.5 mg/dL (=26 µmol/L, SI unit equivalent) ii. AST and ALT = 3 upper limit of normal (ULN), ULN = 5 in case of liver metastasis iii. For subjects with Gilbert's syndrome: total bilirubin <2.5 ULN 7. Adequate renal function at screening Note: Serum creatinine = 1.5 normal institutional limits or calculated (Cockroft- Gault) creatinine clearance = 60 mL/min for subjects with creatinine levels above 1.5 normal institutional limits. 8. Adequate electrolyte profile, defined as absence of clinically significant alterations requiring intravenous corrective measures. Note: Subjects with electrolyte (calcium, potassium and magnesium) alterations considered as not clinically significant as per the investigator assessment may be eligible for the study. 9. Subject must have recovered from all non-haematological toxicities from previous cancer therapies to at least grade 1 (except alopecia) 10. Subject must have measurable disease as per RECIST v1.1 criteria. In Cohort A3, subjects with bone-only metastatic cancer could be eligible provided that they have a lytic or mixed lytic-blastic lesion that can be accurately assessed by CT-scan or MRI. Subjects with blastic bone-only metastasis are not eligible. 11. Non pregnant and adequate method of contraception for female subject of child-bearing potential: i. Negative serum beta human chorionic gonadotropin (ß-HCG) test or negative urine pregnancy test within 72h prior first study treatment administration. ii. Use of an effective method of contraception (hormonal contraception or intra-uterine device) assessed by the investigator, before the first study treatment admini
Exclusion criteria
Exclusion criteria: 15. History of anti-cancer therapies within 4 weeks (or = 5 half lives for targeted agents) of initiating study treatment Note: Anti-cancer therapies are defined as: major surgery, radiotherapy (palliative setting is allowed), hormone therapy, immunotherapy, any conventional cytotoxic chemotherapy or other anti-cancer treatments. For cohorts A1 and A2 only, treatment with hormonal therapy for patients with breast or prostate cancer is allowed during the 4 week window. 16. Known active or uncontrolled infections (bacterial, fungal, viral including HBV and HCV infections) 17. Symptomatic brain metastases, CNS tumors a. In Cohort A3 (exclusion criteria 17a): ii. Subjects with evidence (or history) of brain metastasis could be included provided that they were successfully treated and have been stable for more than 6 months. 18. Symptomatic motor or sensory peripheral neuropathy (= grade 2) (cohorts A1 and A2 only) 19. Subjects having ophthalmologic abnormalities (cohorts A1 and A2 only) Note: Ophthalmologic abnormalities are defined as subjects with monocular vision or having media opacities or any other condition that precludes monitoring of the retina or the fundus or having a history or current ophthalmology exam with retina or cornea abnormalities, especially central serous retinopathy, age related macular degeneration, retina degradation, corneal ulcers, cornea dystrophies or other pathology at the discretion of the ophthalmologist/investigator. 19.a In cohort A3 only : Subjects having rapid progressive ophthalmologic abnormalities will be excuded. 20. Active serious systemic disease (infection, organic or dysmetabolic disease) 21. Subjects with uncontrolled high blood pressure Note: systolic blood pressure, SBP >150 mmHg and/or diastolic blood pressure, DBP > 95 mmHg despite treatment on 2 out of 3 determinations done in case that the first one meets the criterion for exclusion 22. Subjects with Type 1 or 2 diabetes mellitus considered as poorly controlled according to the investigator's judgment (exclusion criteria 22a for cohort A3). Note (cohorts A1 and A2 only): i. Hb A1C = 7% ii. Diabetes mellitus requiring insulin treatment iii. Diabetes mellitus with clinical signs iv. Fasting Plasma Glucose (FPG) = 140 mg/dL / 7.8 mmol/L 23. Serum albumin 470 msec on screening ECG or congenital long QT syndrome (cohorts A1 and A2 only) 29. Subjects who have any medical condition that would, in the investigator's judgment, prevent the subject's participation in the clinical study due to safety concerns or compliance with clinical study procedures. Note: Any severe, acute, or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Phase I : To determine the Maximum Tolerated Dose and schedule (MTDS) and to characterize the dose-limiting toxicities (DLTs), following administration of W0101 given as monotherapy Phase II ( expansion phase): To evaluate the efficacy by Overall Response Rate [ORR%] in subjects with specific tumor types showing IGF-1R overexpression.;Secondary Objective: Phase I : • To evaluate the safety and tolerability of W0101 • To determine the Recommended Dose for Expansion (RDE) cohorts • To evaluate preliminary antitumor activity • To characterize the pharmacokinetics (PK) of tADC, tmAb, cysteine drug linker (F558565) and naked cytotoxic drug (F554443) • To describe the immunogenicity Phase II (expansion phase) : • To evaluate the safety and tolerability profile • To characterize the preliminary antitumor activity by evaluation of progression free survival [PFS] and duration of response [DoR] in subjects with specific tumor types with an overexpression of IGF-1R. • To characterize the pharmacokinetics (PK) of tADC, tmAb, cysteine drug linker (F558565) and naked cytotoxic drug (F554443). • To evaluate the immunogenicity.;Primary end point(s): Dose escalation phase : Dose-limiting toxicities (DLTs) Dose expansion phase : Overall Response Rate ORR [Complete Response + Partial Response] as determined by RECIST v1.1;Timepoint(s) of evaluation of this end point: Dose escalation phase : Will be assesed during the DLT evaluation periods Dose expansion phase : Will be assessed every 6 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Dose escalation phase : - Safety and tolerability profile caracterized by type frequency, severity, intensity (graded by NCI CTCAE version 4.03) - ORR [CR+PR] as determined by RECIST v1.1 - PK parameters - HAHA levels Dose expansion phase : - Safety and tolerability profile caracterized by type frequency, severity, intensity (graded by NCI CTCAE version 4.03) - Progression Free Survival (PFS) - Duration of Response (DoR) - PK parameters - HAHA levels;Timepoint(s) of evaluation of this end point: Along the study | — |
Countries
Belgium, France, Spain
Contacts
Public ContactDr Hatem AZIM
PIERRE FABRE MEDICAMENT
Outcome results
None listed