Inoperable Locally Advanced or Metastatic Solid Tumors advanced cancer metastatic cancer
Conditions
Interventions
XB002 Injection Drug Product will be administered IV over approximately 30
minutes (see Table 11) every three weeks (q3w). Dosing of XB002 will be based
on actual body weight (mg/kg). For subjects w
Sponsors
Exelixis, Inc., Kanika Asija
Eligibility
Age
18 Years to 99 Years
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 at screening is not required for the following subjects: a. Subjects in the Dose-Escalation Stage. b. Subjects with prostate cancer (Cohort I) without soft tissue disease (RECIST 1.1 assessments are not required for these subjects). c. Subjects with primary brain tumors, such as glioblastoma (RECIST assessments are not required for these subjects). 3. Available archival tumor tissue collected no more than 3 years prior to consent, if possible. If archival tumor tissue is not available, a fresh tumor biopsy may be collected from subjects enrolled in the Dose-Escalation Stage and should be collected from subjects in the Cohort-Expansion Stage. Fresh tumor biopsy during the screening period should not be performed for the TA TF+ cohort. Specific requirements for tumor tissue samples are provided in the Laboratory Manual. 4. Recovery to baseline or = 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. Activated partial thromboplastin time (aPTT) × 3 ULN may be allowed at the discretion of the Investigator. f. Total bilirubin = 45 mL/min (>= 0.75 mL/sec) using the Cockcroft-Gault equation h. Urine protein creatinine ratio (UPCR) <= 1.0. 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). • 7
Exclusion criteria
Exclusion criteria: 1. 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. See inclusion criteria #4 for relevant details. 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, port placement) within 7 days before first dose unless discussed with and approved by the Sponsor. Complete wound healing from surgery must have occurred and any surgery related AEs must have resolved before the 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 5.7.7 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Cohort-Expansion Stage (Single-Agent and Combination Therapy Cohorts): To evaluate preliminary efficacy of XB002 when administered alone and in combination therapy by determining the ORR per RECIST 1.1 (or other applicable response criteria, eg, RANO or PCWG3 criteria) as assessed by the Investigator. | — |
Secondary
| Measure | Time frame |
|---|---|
| • 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 (or other applicable response criteria, eg, RANO or PCWG3 criteria) 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 (or other applicable response criteria, eg, RANO or PCWG3 criteria) as assessed by a BIRC for selected cohorts • To evaluate overall survival • To evaluate changes in tumor markers from baseline for selected tumor indications | — |
Countries
Netherlands
Outcome results
None listed