Advanced solid tumors for whom life-prolonging therapies do not exist or available therapies are intolerable or no longer effective. Single-agent XB002 will be evaluated up to 10 tumor types, and combination treatment will also be evaluated with nivolumab in NSCLC, SCCHN, and esophageal SCC. MedDRA version: 23.0 Level: PT Classification code 10083234 Term: Hormone receptor positive breast cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: XB002
Product Code: XB002
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: antibody-drug conjugate (ADC) XB002
Current Sponsor code: XB002
Concentration unit: mg/ml milli
Sponsors
Exelixis, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Cytologically or histologically and radiologically confirmed solid tumor that is inoperable, locally advanced, metastatic, or recurrent. 2. Subjects in the Cohort-Expansion Stage must have measurable disease per RECIST 1.1 as determined by the investigator. Note: Measurable disease is not required for subjects in the Dose-Escalation Stage. 3. Available archival tumor tissue collected approximately 2 years prior to consent. If archival tumor tissue is not available, a fresh tumor biopsy may be collected from subjects enrolled in the Dose-Escalation Stage and must be collected from subjects in the Cohort-Expansion Stage, at least 7 days (and up to 60 days) prior to first dose. Specific requirements for tumor tissue samples are provided in the Laboratory Manual. 4. Recovery to baseline or = Grade 1 severity (Common Terminology Criteria for Adverse Events version 5 [CTCAE v5]) from AEs, unless AEs are clinically nonsignificant (eg, alopecia) or stable (eg, Grade 1 peripheral neuropathy). 5. Age 18 years or older on the day of consent. 6. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1. 7. Adequate organ and marrow function, based upon meeting all of the following laboratory criteria within 10 days before first dose of study treatment: a. Absolute neutrophil count (ANC) = 1500/mm3 (= 1.5 GI/L) without granulocyte colony-stimulating factor (G-CSF) support within 2 weeks prior to screening laboratory sample collection. b. Platelets = 100,000/mm3 (= 100 GI/L)] without transfusion within 2 weeks prior to screening laboratory sample collection. c. Hemoglobin = 9 g/dL (= 90 g/L) without transfusion within 2 weeks prior to screening laboratory sample collection. d. Prothrombin time (PT) or activated partial thromboplastin time (aPTT) = 1.2 × upper limit of normal (ULN) or International Normalized Ratio (INR) = 1.3 without anticoagulation therapy (INR = 3 if on stable oral coumarin-based anticoagulant). e. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) = 3 × ULN. f. Total bilirubin = 1.5 × ULN (for subjects with known Gilbert’s disease, total bilirubin = 3 × ULN). g. Serum creatinine = 1.5 × ULN or calculated creatinine clearance = 45 mL/min (= 0.75 mL/sec) using the Cockcroft-Gault equation 8. Capable of understanding and complying with the protocol requirements and must have signed the informed consent document. 9. Sexually active fertile subjects and their partners must agree to highly effective methods of contraception (defined in Appendix E) during the course of the study and for the following durations after the last dose of treatment (whichever is later): • 4 months after the last dose of XB002 for women of childbearing potential (WOCBP) and men, or • 5 months after the last dose of nivolumab for women An additional contraceptive method, such as a barrier method (eg, condom), is recommended. 10. Female subjects of childbearing potential must not be pregnant at screening. Female subjects are considered to be of childbearing potential unless one of the following criteria is met: permanent sterilization (hysterectomy, bilateral salpingectomy, or bilateral oophorectomy) or documented postmenopausal status Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 180 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 271
Exclusion criteria
Exclusion criteria: Receipt of any tissue factor-targeting antibody drug conjugate or auristatin derivate based antibody drug conjugate. 2. Receipt of any chemotherapy or anticancer antibody (eg, anti-VEGF mAb, antibody-drug conjugate, or PD-1/PD-L1 mAb) within 21 days (nitrosoureas or mitomycin within 42 days) before first dose of study treatment. 3. Receipt of any type of small molecule kinase inhibitor (including investigational kinase inhibitors) within 2 weeks before first dose of study treatment. 4. Receipt of any anticancer hormonal therapy within 2 weeks or within 5 half-lives of the agent, whichever is shorter, before first dose of study treatment. Note: Concomitant use of a luteinizing hormone-releasing hormone (LHRH) agonist (eg, leuprolide, goserelin) or antagonist (eg, relugolix) is permitted. 5. Radiation therapy within 2 weeks before first dose of study treatment. Subjects with clinically relevant ongoing complications (eg, radiation induced esophagitis or pneumonitis) from prior radiation therapy are not eligible. 6. Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery (including radiosurgery) and stable for at least 4 weeks before first dose of study treatment. Note: Eligible subjects must be neurologically asymptomatic and without corticosteroid treatment at the time of first dose of study treatment. 7. The subject has uncontrolled, significant intercurrent or recent illness 8. Major surgery (eg, GI surgery, removal or biopsy of brain metastasis) within 4 weeks before first dose of study treatment. Minor surgery (eg, simple excision, tooth extraction, biopsies) within 7 days before first dose. Complete wound healing from surgery must have occurred before first dose. Subjects with clinically relevant ongoing complications from prior surgery are not eligible. 9. Corrected QT interval calculated by the Fridericia formula (QTcF) > 480 ms per electrocardiogram (ECG) within 4 weeks before first dose of study treatment (see Section 5.6.6 for Fridericia formula). Note: If a single ECG shows a QTcF with an absolute value > 480 ms, two additional ECGs at intervals of approximately 3 minutes must be performed within 30 minutes after the initial ECG, and the average of the three consecutive results for QTcF must be = 480 ms for the subject to be eligible. 10. History of psychiatric illness likely to interfere with ability to comply with protocol requirements or give informed consent. 11. Pregnant or lactating females. 12. Previously identified allergy or hypersensitivity to components of the study treatment formulations or history of severe infusion-related reactions (IRRs) to monoclonal antibodies. 13. Diagnosis of another malignancy within 2 years before first dose of study treatment, except for superficial skin cancers, or localized, low grade tumors deemed cured and not treated with systemic therapy.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Cohort-Expansion Stage (Single-Agent and Combination Therapy Cohorts): Primary: •To evaluate the preliminary efficacy of XB002 when administered alone and in combination therapy by estimating the ORR per RECIST 1.1 as assessed by the Investigator;Secondary Objective: •To evaluate the safety and tolerability of XB002 when administered alone and in combination therapy •To further evaluate the PK of XB002 (antibody conjugated to payload), total antibody (unconjugated and conjugated antibody), and free payload following IV administration alone and in combination therapy •To assess the immunogenicity of XB002 •To evaluate the anti-tumor activity of XB002 alone and in combination therapy as measured by DOR and PFS per RECIST 1.1 as assessed by the Investigator •To evaluate the anti-tumor activity of XB002 alone and in combination therapy as measured by ORR, DOR, and PFS per RECIST 1.1 as assessed by a Blinded Independent Radiology Committee (BIRC) for selected cohorts •To evaluate overall survival •To evaluate changes in tumor markers from baseline for selected tumor indications ;Primary end point(s): Cohort-Expansion Stage (Single-Agent and Combination Therapy Cohorts): To evaluate preliminary efficacy of XB002 when administered alone and in combination therapy by estimating the ORR per RECIST 1.1 as assessed by the Investigator;Timepoint(s) of evaluation of this end point: The confirmation must have occurred on a subsequent visit that was = 28 days after the response was first observed. Point estimates and 90% exact CIs for ORR will be evaluated independently within each of the dose escalation and expansion cohorts. Please refer to protocol. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • To evaluate the safety and tolerability of XB002 when administered alone and in combination therapy • To further evaluate the PK of XB002 (antibody conjugated to payload), total antibody (unconjugated and conjugated antibody), and free payload following IV administration alone and in combination therapy • To assess the immunogenicity of XB002 • To evaluate the anti-tumor activity of XB002 alone and in combination therapy as measured by DOR and PFS per RECIST 1.1 as assessed by the Investigator • To evaluate the anti-tumor activity of XB002 alone and in combination therapy as measured by ORR, DOR, and PFS per RECIST 1.1 as assessed by a BIRC for selected cohorts • To evaluate overall survival • To evaluate changes in tumor markers from baseline for selected tumor indications ;Timepoint(s) of evaluation of this end point: Please refer to protocol | — |
Countries
Australia, Belgium, France, Germany, Italy, Netherlands, Spain, United Kingdom, United States
Contacts
Public ContactExelixis Medical Affairs
Exelixis, Inc.
Outcome results
None listed