Advanced or metastatic solid tumors (excluding lymphoma) MedDRA version: 20.0 Level: LLT Classification code 10065252 Term: Solid tumor System Organ Class: 100000020962
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 Note: preferentially squamous non-small cell lung cancer, larynx carcinoma, ER positive breast cancer and soft tissue sarcomas 3. Formalin-fixed paraffin-embedded (FFPE) archived tumor tissue block available (cohorts A1 and A2) for retrospective assessment of IGF-1R status 4. ECOG performance status 0 or 1 5. Adequate bone marrow at screening and at baseline i. Absolute neutrophil count (ANC) = 1,500/mm3 ii. Platelet count = 150,000/mm3 iii. Hemoglobin = 9g/dL(6.2 mmol/L) Note: Any blood product transfusion is prohibited within 2 weeks before the first study treatment administration. 6. Adequate liver function at screening and at baseline i. Total Bilirubin = 1.5 mg/dL (=26µmol/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 and at baseline 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. Serum calcium potassium and magnesium within normal ranges as per local lab values at screening and at baseline. Note: Subjects with electrolyte (calcium potassium and magnesium) grade 1 alterations considered as not clinically significant as per the investigator assessment may be eligible for the study. 9. Subject must have recovered from all toxicities from previous cancer therapies toxicity to at least grade 1 (except alopecia) 10. Subject must have measurable disease as per RECIST v1.1 criteria 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, for at least 2 months before the first study treatment administration, and agreement to go on using it during the whole duration of the study and up to 3 month after the last dose of the study treatment Note: a female subject of child-bearing potential is a woman who is not permanently sterilized or not postmenopausal (post-menopausal is defined as 12 months with no menses without an alternative medical cause). 12. Adequate method of contraception for fertile male with a child-bearing potential partner. Note: Use of double barrier contraception method (use of condom for male and effective contraception method for the partner) from the entire duration of the study to 3 months after the last dose of the study treatment. 13. Having signed his/her written informed consent, prior to any screening procedure 14. Affiliated or beneficiary of a social security system, (if applicable in the national regulation) + Expansion cohorts phase (II) The same inclusion criteria listed above apply for expansion cohort phase, except for inclusion criteria 2 and 3, which are replaced by: 2. Subjects with histologically or cytologically confirmed advanced or metastatic specific solid tumor 3. Su
Exclusion criteria
Exclusion criteria: 1. 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 (except treatment for prostatic and breast cancer), immunotherapy, any conventional cytotoxic chemotherapy or other anti-cancer treatments 2. Known active or uncontrolled infections (bacterial, fungal, viral including HBV and HCV infections) 3. Symptomatic brain metastases, CNS tumors 4. Symptomatic motor or sensory peripheral neuropathy (= grade 2) 5. Subjects having ophthalmologic abnormalities 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. 6. Active serious systemic disease (infection,organic or dysmetabolic desease) 7. 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 8. Type 1 diabetes or type 2 diabetes that is poorly controlled according to the investigator’s judgment 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 9. Serum albumin 470 msec on screening ECG or congenital long QT syndrome 15. 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 study treatment administration or that may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for the study 16. Prior anti IGF-1R therapy 17. Subject liable not to comply with protocol instructions in the investigator’s opinion 18. Subject linguistically or mentally unable to understand the nature, objectives and possible consequences of the trial, or refusing to subject himself/herself to its constraints 19. Subject family member or work associate (secretary, nurse, techni
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Dose escalation phase : To determine the Maximum Tolerated Dose and schedule (MTDS) and to characterize the dose-limiting toxicities (DLTs), following administration of W0101 given as monotherapy intravenous infusion. Dose expansion phase: To evaluate the efficacy by Overall Response Rate [ORR%] in subjects with specific tumor types selected through high expression of IGF-1R;Secondary Objective: Dose escalation phase : To evaluate the safety and tolerability of W0101 To evaluate preliminary antitumor activity To characterize the pharmacokinetics (PK) To describe the immunogenicity To determine the Recommended Dose for Expansion (RDE) cohorts Dose 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 selected through high expression of IGF-1R To characterize the pharmacokinetics (PK) 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
France, Spain
Contacts
Public ContactDr Karim KEDDAD
PIERRE FABRE MEDICAMENT
Outcome results
None listed