E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Metastatic or locally advanced unresectable solid tumors in following indications: breast carcinoma (BC), castration-resistant prostate carcinoma, non-small cell lung carcinoma (NSCLC), epithelial ovarian carcinoma (EOC), endometrial carcinoma, head and neck squamous cell carcinoma (HNSCC), or cholangiocarcinoma |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10065147 |
E.1.2 | Term | Malignant solid tumor |
E.1.2 | System Organ Class | 100000004864 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective of Part A is to determine the safety profile of CX-2009, the maximum tolerated dose (MTD) / Recommended Phase 2 Dose (RP2D), and the dose-limiting toxicities (DLTs) of CX-2009, when administered intravenously (IV) every 21 days as monotherapy to subjects with selected advanced or recurrent solid tumors. The primary objectives of Part A2 are to: •Characterize the protease activity and measure the cleavage of CX-2009 in tumor biopsies and peripheral blood in subjects with demonstrated high tumor expression of CD166 by immunohistochemistry (IHC); and •Obtain additional characterization of the safety of CX-2009 when administered as monotherapy at dose levels evaluated in Part A.
The primary objective of Part B is to evaluate the efficacy of CX-2009 when administered IV as monotherapy at the MTD/RP2D (as defined in consideration of available data from Part A and Part A2) in subjects with selected advanced or recurrent solid tumors.
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E.2.2 | Secondary objectives of the trial |
Evaluate preliminary efficacy in subjects treated with CX-2009 as monotherapy; Characterize the pharmacokinetics (PK) of CX-2009; Assess the incidence of anti-drug antibody (ADA) formation to CX-2009; Obtain additional characterization of the safety of CX-2009 at the MTD/RP2D; Evaluate efficacy in subjects treated with CX-2009 as monotherapy.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Histologically confirmed diagnosis of active metastatic or locally advanced unresectable solid tumor in Subjects who have disease progression after treatment with available therapies that are known to confer clinical benefit, or who are intolerant to treatment in following indications: - For Part A and Part B: breast carcinoma, castration-resistant prostate cancer, non-small cell lung cancer (incl adenocarcinoma and squamous cell subtypes), overian carcinoma, endometrial carcinoma, head and neck squamous cell carcinoma, cholangiocarcinoma - For Part A2 only: breast carcinoma, Non-small cell lung cancer, ovarian carcinoma, head and neck squamous cell carcinoma and endometrial carcinoma 2. Agrees to provide tumor tissue, archival, new or recent acquisition confirmed to be available prior to initiation of study drug for performance of correlative tissue and cellular studies from a tumor site not previously irradiated 3. Evaluable or measurable disease for dose escalation part A and measurable disease required for dose expansion cohorts part B 4. Subjects with treated brain metastases are eligible if brain metastases are stable and subject does not require radiation therapy or steroids. Active screening for brain metastases is not required. 5. At least 18 y of age 6. Eastern Cooperative Oncology Group performance status of 0 or 1 7. Anticipated life expectancy of at least 3 months 8. screening lab values must meet following criteria: absolute neutrophil count >=1500µl; platelet count >= 100 x 10³/µl (must not have been transfused within prev. 10 days); hemoglobin >=9.0 g/dL (may have been transfused); serum creatinine <= 1.5 x institution upper limit of normal (ULN); aspartate aminotransferase (AST) <= 2.5xinstitution's ULN; alanine aminotransferase (ALT) <= 2.5x institution's ULN (AST, ALT <5 x ULN for subjects with CCC and liver metastases); and serum total bilirubin <= 1.5x institutional ULN (total bilirubin must be <=3x institution's ULN in subjects with Gilbert's syndrome). Serum total bilirubin <= 3.0 x institutional ULN for subjects with CCC and liver metastasis 9. Women of childbearing potential (defined as women who have experienced menarche and who are not permanently sterile or postmenopausal; postmenopausal is defined as 12 consecutive months with no menses without an alternative medical cause), and males must agree to use a highly effective method of contraception prior to study entry, while on study drug and for a period of 50 days following the last treatment; highly effective methods of contraception which result in a low failure rate (ie <1 % per year) when used consistently and correctly include implants, injectables, combined hormonal contraceptives, some IUD's, sexual abstinence or a vasectomized partner - True abstinence, when in line with the preferred and usual lifestyme of the subjects is considered a highly effective method only if defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatments. (periodic abstinence and withdrawal are not acceptable methods of contraception) 10. The ability to understand and the willingness to sign a written informed consent document and adhere to study schedule and prohibitions |
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E.4 | Principal exclusion criteria |
1. Neuropathie > grade 1 2. Active chronic corneal disorder, including but not limited to the following: sjogren's syndrome, Fuchs corneal dystropathy (requiring treatment), history of corneal transplantation, active herpetic keratitis, and also active ocular conditions requiring ongoing treatment/monitoring such as wet age-related macular degeneration requiring intravitreal injections, active diabetic retinopathy with macular edema, presensce of papilledema and acquired monocular vision 3. Serious concurrent illness, including, but not limited to following: - clinically relevant active infection including known active hepatitis B or C. HIV infection or CMV infection or any other known concurrent infectious disease requiring IV antibiotics within 2 weeks of study enrollment - history of or current active autoimmune diseases, including but not limited to inflammatory bowel diseases, RA, autoimmune thyroiditis which is not a sequela of prior immune checkpoint therapy, autoimmune hepatitis, systemic sclerosis, systemic lupus erythematosus, autoimmune vasculitis, autoimmune neuropathies or type 1 insuline dependent diabetes mellitus - significant cardiac disease such as recent MI (<= 6 months prior to day 1), unstable angina pectoris, uncontrolled congestive heart failure (NY Heart association >class II), uncontrolled hypertension (NCI CTCAE v.4.03 grade 3 or higher), uncontrolled cardiac arrythmias, severe aortic stenosis or >= grade 3 cardiac toxicity following prior chemotherapy - History of multiple sclerosis or other demyelinating disease, Eaton-Lambert syndrome (para-neoplastic syndrome), history of hemorrhagic or ischemic stroke within the last 6 months, or alcoholic liver disease - Non-healing wound(s) or ulcer(s) except for ulcerative lesions caused by the underlying neoplasm - Psychiatric illness/social situations that would limit compliance with study requirements - Interstitial lung disease irrespective of etiology 4. Advanced or metastatic Stage IV NSCLC subjects with epidermal growth factor receptor or anaplastic lymphoma kinase genomic alterations unless they have progressed on treatment with appropriate targeted therapy, including osimertinib for T790M mutation-positive NSCLC 5. Any other anti-cancer treatment such as chemotherapy, immunotherapy, biochemotherapy, radiotherapy, investigative therapy, or high-dose steroids within 30 days of receiving study drug. Low-dose steroids, luteinizing hormone-releasing hormone, aromatase inhibitors (eg, anastrozole), at doses that have been stable for 30 days are permitted for subjects with CRPC 6. History of severe allergic or anaphylactic reactions to previous monoclonal antibody therapy 7. Prior treatment with maytansinoid-containing drug conjugates 8. Subjects with a previously documented absence of thiol-S-purine methyltransferase activity 9. Unresolved acute toxicity NCI CTCAE v4.03 Grade >1 (or baseline, whichever is greater) from prior anti-cancer therapy. Alopecia and other non-acute toxicities are acceptable 10. History of malignancy that is active within the previous 2 years except for localized cancers that are not related to the current cancer being treated, are considered to have been cured and in the opinion of the Investigator, present a low risk for recurrence, including basal or squamous cell skin cancer, superficial bladder cancer or carcinoma in situ of the prostate, cervix or breast 11. Currently receiving anticoagulation therapy with warfarin 12. The subject has undergone major surgery (requiring general anesthesia) within 3 months prior to dosing. Subjects who have undergone major surgery within this time period may be enrolled, if, in the Investigator’s judgment, wound healing has largely resolved 13. Subjects who have received a live vaccine 28 days prior to the planned first dose of CX-2009, while on study drug, will be excluded, and for 90 days after the last dose of CX-2009. 14. Participating in an ongoing clinical study involving treatment with medications, radiation, or surgery 15. Women who are pregnant or breast feeding 16. Subjects who are >20% below their ideal body weight |
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E.5 End points |
E.5.1 | Primary end point(s) |
Dose-limiting toxicities Study-drug related AEs and AEs leading to discontinuation Changes from baseline in clinical laboratory results and vital signs |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Administrative interim analyses on safety and efficacy or on PK, immunogenicity, and selected biomarkers may be performed at several times prior to completion of the study in order to facilitate program decisions and to support study presentations or publications
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E.5.2 | Secondary end point(s) |
Secondary objectives: Part A & A2: - Evaluate preliminary efficacy in subjects treated with CX-2009 based on ORR, TTR, DOR, PFS & OS. - Characterize PK of CX-2009 with respect to following analytes: Intact CX-2009, Total CX-2009, Total CX-2009 conjugated DM4, Free DM4 and S-Methyl DM4 (DM4-Me) - Assess incidence of ADA formation to CX-2009 Part B: - Obtain additional characterization of safety of CX-2009 at the MTD/RP2D - Evaluate efficacy on the basis of DOR, PFS & OS - Characterize PK of CX-2009 - Assess the incidence of ADA formation to CX-2009 |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Administrative interim analyses on safety and efficacy or on PK, immunogenicity, and selected biomarkers may be performed at several times prior to completion of the study in order to facilitate program decisions and to support study presentations or publications
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | Yes |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 16 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Germany |
Netherlands |
Spain |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 6 |