Study of XB002 in Subjects With Solid Tumors (JEWEL-101)
- Conditions
- Endometrial CancerEsophageal SCCEpithelial Ovarian CancerNon Small Cell Lung CancerPancreatic CancerCervical CancerSCCHNTriple Negative Breast CancerHormone Receptor-positive Breast CancerTissue Factor-Expressing Solid Tumors
- Interventions
- Drug: XB002Drug: Nivolumab
- Registration Number
- NCT04925284
- Lead Sponsor
- Exelixis
- Brief Summary
This is a Phase 1, open-label, multicenter, dose-escalation and expansion study evaluating the safety, tolerability, PK, pharmacodynamics, and clinical antitumor activity of XB002 administered IV q3w alone and in combination with nivolumab to subjects with advanced solid tumors.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 573
- Cytologically or histologically and radiologically confirmed solid tumor that is inoperable, locally advanced, metastatic, or recurrent.
- Dose-Escalation Stage Cohorts A and AN: The subject has received atleast one systemic standard life-prolonging therapy unless it does not exist, or available therapies are intolerable or no longer effective.
- Cohort-Expansion Stage (Cohorts B - M, BN, FN and HN): The subject has received standard life-prolonging therapies unless they do not exist, or available therapies are intolerable or no longer effective.
- Cohort-Expansion Stage Cohort B and BN (Non-small Cell Lung Cancer): Subjects with Stage IV NSCLC who have documented radiographic disease progression during or following their last systemic anticancer therapy.
- Cohort-Expansion Stage Cohort D (Epithelial Ovarian Cancer): Subjects with high-grade serous ovarian cancer, including primary peritoneal cancer (PPC) and fallopian tube cancer (FTC) who have platinum-resistant disease following treatment with platinum-containing chemotherapy.
- Cohort-Expansion Stage Cohort E (Cervical Cancer): Subjects with persistent, recurrent, or metastatic carcinoma of the uterine cervix who have documented radiographic disease progression during or following their last systemic anticancer therapy.
- Cohorts F and FN (SCCHN): Subjects with head and neck cancer (squamous cell histology) who have documented radiographic disease progression during or following their last systemic anticancer therapy. Allowed primary tumor locations are oral cavity, oropharynx, hypopharynx, glottic larynx. Note: Excluded are subjects with primary tumor site of the nasopharynx.
- Cohort G (Pancreatic Cancer): Subjects with pancreatic cancer (adenocarcinoma histology) who have documented radiographic disease progression during or following their last systemic anticancer therapy.
- Cohorts H and HN (Esophageal SCC): Subjects with esophageal cancer (squamous cell histology) who have documented radiographic disease progression during or following their last systemic anticancer therapy. Note: subjects with esophageal adenocarcinoma and adenocarcinoma of gastroesophageal junction (GEJ) are excluded.
- Cohort I (mCRPC): Subjects with metastatic, castration resistant adenocarcinoma of the prostate. Note: Neuroendocrine differentiation and other histological features are permitted if adenocarcinoma is the primary histology.
- Cohort J (TNBC): Subjects with triple-negative (estrogen receptor negative [ER-]/progesterone receptor negative [PR-]/ human epidermal growth factor receptor 2 negative [HER-2-]) breast cancer who have documented radiographic disease progression during or following their last systemic anticancer therapy for inoperable locally advanced or metastatic disease.
- Cohort K (HR + BC): Subjects with breast cancer that is hormone receptor-positive (ER+ and/or PR+) and HER-2-) and who have documented radiographic disease progression during or following their last systemic anticancer therapy for inoperable locally advanced or metastatic disease.
- Cohort L (Endometrial Cancer): Subjects with locally advanced, recurrent or metastatic endometrial cancer who have documented radiographic disease progression during or following their last systemic anticancer therapy.
- Cohort M (Tumor-Agnostic Tissue Factor-Expressing Solid Tumors): Subjects with solid tumors other than those designated in Cohorts B-L and those which express tissue factor. Participation in this cohort will be at selected sites and countries based on site feasibility assessment.
- Expansion Cohorts: Subjects must have measurable disease per RECIST 1.1 as determined by the Investigator, except for subjects with prostate cancer without soft tissue disease and subjects with primary brain tumors.
- Tumor tissue material 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.
- Recovery to baseline or ≤ Grade 1 severity (Common Terminology Criteria for Adverse Events version 5 [CTCAE v5]) from AEs.
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1.
- Adequate organ and marrow function.
- Sexually active fertile subjects and their partners must agree to use medically accepted methods of contraception.
- Female subjects of childbearing potential must not be pregnant at screening.
- Receipt of prior therapies as defined in study protocol
- 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.
- Uncontrolled, significant intercurrent or recent illness.
- Major surgery within 4 weeks before first dose of study treatment
- Corrected QT interval calculated by the Fridericia formula (QTcF) > 480 ms per electrocardiogram (ECG).
- Pregnant or lactating females
- Previously identified allergy or hypersensitivity to components of study treatment formulations or history of severe infusion-related reactions to monoclonal antibodies.
- Another unresolved malignancy or a malignancy that is considered to be cured within 2 years before first dose of study treatment. Note: Subjects with superficial non-melanoma skin cancers, or localized, low grade tumors deemed cured and not treated with systemic therapy within 2 years before first dose of study treatment are eligible.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description XB002 Single-Agent Dose-Escalation Cohorts XB002 Subjects (Cohort A) will accrue in cohorts of 3-12 subjects in a modified i3+3 design. XB002 + Nivolumab Dose Escalation Cohorts Nivolumab Subjects (Cohort AN) will accrue in cohorts of 3-12 subjects in a modified i3+3 design. XB002 + Nivolumab Dose Escalation Cohorts XB002 Subjects (Cohort AN) will accrue in cohorts of 3-12 subjects in a modified i3+3 design. XB002 + Nivolumab Dose Expansion Cohorts XB002 The MTD or recommended dose from the dose-escalation stage may be further explored in subjects with non-small cell lung cancer \[NSCLC\] (Cohort BN), SCCHN (Cohort FN), Esophageal SCC (Cohort HN). XB002 Single-Agent Expansion Cohorts XB002 The MTD or recommended dose from the dose-escalation stage may be further explored in subjects with non-small cell lung cancer \[NSCLC\] (Cohort B), epithelial ovarian cancer (Cohort D), cervical cancer (Cohort E), SCCHN (Cohort F), pancreatic cancer (Cohort G), Esophageal SCC (Cohort H), metastatic castration-resistant prostate cancer (Cohort I), triple-negative breast cancer (Cohort J), hormone-receptor positive breast cancer (Cohort K), endometrial cancer (Cohort L) and tumor agnostic tissue factor-expressing solid tumors (Cohort M). XB002 + Nivolumab Dose Expansion Cohorts Nivolumab The MTD or recommended dose from the dose-escalation stage may be further explored in subjects with non-small cell lung cancer \[NSCLC\] (Cohort BN), SCCHN (Cohort FN), Esophageal SCC (Cohort HN).
- Primary Outcome Measures
Name Time Method Dose-Escalation Stage: MTD/recommended dose for XB002 18 months To determine the MTD and/or RD for further evaluation of IV administration of XB002 alone and in combination therapy in subjects with advanced malignancies
Cohort-Expansion Stage: Objective Response Rate (ORR) 12 months 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 Outcome Measures
Name Time Method Immunogenicity of XB002 30 months To assess the immunogenicity of XB002 as measured by anti-drug antibody (ADA) analysis
Tolerability of XB002 as evaluated by the duration of exposure for the study 30 months To evaluate the tolerability of XB002 through the evaluation of duration of exposure for the study treatment
Tolerability of XB002 as evaluated dose intensity of the study treatment 30 months To evaluate the tolerability of XB002 through the evaluation of dose intensity of the study treatment
Safety of XB002: Adverse Events 30 months To evaluate the safety of XB002 through the evaluation of incidence and severity of nonserious adverse events (AEs) and serious adverse events (SAEs)
Anti-tumor activity of XB002: Objective Response Rate (ORR) 30 months To evaluate the anti-tumor activity of XB002, as measured by ORR, per RECIST 1.1 (or other applicable response criteria eg. RANO or PCWG3 criteria) as assessed by the Investigator (dose escalation stage) or by a BIRC for selected cohorts (cohort expansion stage).
Trough Concentration (Ctrough) 30 months To evaluate the Ctrough of XB002, total antibody, and free payload at scheduled visits over time
Anti-tumor activity of XB002: Duration of Response (DOR) 30 months To evaluate the anti-tumor activity of XB002, as measured by DOR, per RECIST 1.1 (or other applicable response criteria eg. RANO or PCWG3 criteria) as assessed by the Investigator (dose escalation stage) or by a BIRC for selected cohorts (cohort expansion stage)
Anti-tumor activity of XB002: Progression Free Survival (PFS) 30 months To evaluate the anti-tumor activity of XB002, as measured by PFS, per RECIST 1.1 (or other applicable response criteria eg. RANO or PCWG3 criteria) as assessed by the Investigator (dose escalation stage) or by a BIRC for selected cohorts (cohort expansion stage)
Cohort-Expansion Stage: overall survival 12 months To evaluate overall survival
Maximum Plasma Concentration (Cmax) 30 months To evaluate the Cmax for XB002, total antibody, and free payload at scheduled visits over time
Trial Locations
- Locations (95)
Exelixis Clinical Site #29
🇺🇸Cleveland, Ohio, United States
Exelixis Clinical Site #20
🇺🇸Tucson, Arizona, United States
Exelixis Clinical Site#58
🇺🇸Little Rock, Arkansas, United States
Exelixis Clinical Site#59
🇺🇸Fountain Valley, California, United States
Exelixis Clinical Site#95
🇺🇸Tucson, Arizona, United States
Exelixis Clinical Site #21
🇺🇸Los Angeles, California, United States
Exelixis Clinical Site #26
🇺🇸Los Angeles, California, United States
Exelixis Clinical Site #22
🇺🇸Washington, District of Columbia, United States
Exelixis Clinical Site #16
🇺🇸New Haven, Connecticut, United States
Exelixis Clinical Site #6
🇺🇸Baltimore, Maryland, United States
Exelixis Clinical Site #18
🇺🇸Columbia, Maryland, United States
Exelixis Clinical Site#93
🇺🇸Chicago, Illinois, United States
Exelixis Clinical Site #25
🇺🇸Boston, Massachusetts, United States
Exelixis Clinical Site #5
🇺🇸Saint Louis, Missouri, United States
Exelixis Clinical Site #8
🇺🇸East Brunswick, New Jersey, United States
Exelixis Clinical Site #23
🇺🇸Albany, New York, United States
Exelixis Clinical Site #7
🇺🇸New Brunswick, New Jersey, United States
Exelixis Clinical Site#67
🇺🇸Lake Success, New York, United States
Exelixis Clinical Site #12
🇺🇸New York, New York, United States
Exelixis Clinical Site #15
🇺🇸Cleveland, Ohio, United States
Exelixis Clinical Site #24
🇺🇸Austin, Texas, United States
Exelixis Clinical Site #49
🇺🇸Hilliard, Ohio, United States
Exelixis Clinical Site #1
🇺🇸Austin, Texas, United States
Exelixis Clinical Site #32
🇺🇸Dallas, Texas, United States
Exelixis Clinical Site #14
🇺🇸Dallas, Texas, United States
Exelixis Clinical Site#75
🇦🇺Miranda, New South Wales, Australia
Exelixis Clinical Site #9
🇺🇸Charlottesville, Virginia, United States
Exelixis Clinical Site #35
🇦🇺Saint Leonards, Australia
Exelixis Clinical Site #37
🇦🇺Darlinghurst, Australia
Exelixis Clinical Site #44
🇦🇺Liverpool, Australia
Exelixis Clinical Site#71
🇧🇪Charleroi, Hainaut, Belgium
Exelixis Clinical Site#66
🇧🇪Liège, Liege, Belgium
Exelixis Clinical Site#69
🇫🇷Lyon, Rhone-Alpes, France
Exelixis Clinical Site #45
🇫🇷Bordeaux, France
Exelixis Clinical Site #50
🇫🇷Rennes, France
Exelixis Clinical Site #41
🇫🇷Pierre Benite, France
Exelixis Clinical Site#68
🇫🇷Poitiers, France
Exelixis Clinical Site#63
🇫🇷Strasbourg, France
Exelixis Clinical Site#84
🇮🇹Milan, Italy
Exelixis Clinical Site#62
🇮🇹Milano, MI, Italy
Exelixis Clinical Site#53
🇫🇷Villejuif, France
Exelixis Clinical Site #54
🇮🇹Ancona, Italy
Exelixis Clinical Site#60
🇮🇹Firenze, Italy
Exelixis Clinical Site #40
🇮🇹Roma, Italy
Exelixis Clinical Site#90
🇮🇹Roma, Italy
Exelixis Clinical Site #34
🇮🇹Rozzano, Italy
Exelixis Clinical Site#61
🇮🇹Siena, Italy
Exelixis Clinical Site#80
🇰🇷Seongnam-si, Gyeonggi-Do, Korea, Republic of
Exelixis Clinical Site#79
🇰🇷Anyang-si, Gyeonggi-do, Korea, Republic of
Exelixis Clinical Site#74
🇰🇷Seongnam-si, Gyeonggido [Kyonggi-do], Korea, Republic of
Exelixis Clinical Site#94
🇰🇷Seoul, Seoul Teugbyeolsi [Seoul-T'ukpyolshi], Korea, Republic of
Exelixis Clinical Site#83
🇰🇷Suwon, Gyeonggido [Kyonggi-do], Korea, Republic of
Exelixis Clinical Site#78
🇰🇷Hwasun, Jeonranamdo [Chollanam-do], Korea, Republic of
Exelixis Clinical Site#81
🇰🇷Seoul, Seoul Teugbyeolsi [Seoul-T'ukpyolshi], Korea, Republic of
Exelixis Clinical Site#73
🇳🇱Amsterdam, Noord-Holland, Netherlands
Exelixis Clinical Site#85
🇰🇷Seoul, Seoul Teugbyeolsi [Seoul-T'ukpyolshi], Korea, Republic of
Exelixis Clinical Site #27
🇪🇸Barcelona, Spain
Exelixis Clinical Site#76
🇳🇱Rotterdam, Zuid-Holland, Netherlands
Exelixis Clinical Site#65
🇳🇱Groningen, Netherlands
Exelixis Clinical Site #36
🇪🇸Barcelona, Spain
Exelixis Clinical Site#55
🇪🇸Barcelona, Spain
Exelixis Clinical Site#64
🇪🇸Madrid, Spain
Exelixis Clinical Site#82
🇪🇸Barcelona, Spain
Exelixis Clinical Site #31
🇪🇸Lleida, Spain
Exelixis Clinical Site #33
🇪🇸Madrid, Spain
Exelixis Clinical Site #17
🇪🇸Madrid, Spain
Exelixis Clinical Site #42
🇪🇸Madrid, Spain
Exelixis Clinical Site #46
🇪🇸Málaga, Spain
Exelixis Clinical Site #13
🇪🇸Madrid, Spain
Exelixis Clinical Site #43
🇪🇸Valencia, Spain
Exelixis Clinical Site #51
🇪🇸Valencia, Spain
Exelixis Clinical Site#89
🇬🇧London, England, United Kingdom
Exelixis Clinical Site#88
🇬🇧Leicester, England, United Kingdom
Exelixis Clinical Site#72
🇪🇸Zaragoza, Spain
Exelixis Clinical Site #52
🇬🇧Glasgow, United Kingdom
Exelixis Clinical Site#91
🇬🇧Cardiff, Wales, United Kingdom
Exelixis Clinical Site #28
🇬🇧Newcastle Upon Tyne, United Kingdom
Exelixis Clinical Site#57
🇬🇧London, United Kingdom
Exelixis Clinical Site #3
🇺🇸Nashville, Tennessee, United States
Exelixis Clinical Site#92
🇺🇸Houston, Texas, United States
Exelixis Clinical Site #2
🇺🇸San Antonio, Texas, United States
Exelixis Clinical Site#70
🇦🇺Nedlands, Western Australia, Australia
Exelixis Clinical Site #30
🇧🇪Brussels, Belgium
Exelixis Clinical Site #47
🇧🇪Edegem, Belgium
Exelixis Clinical Site#56
🇧🇪Brussels, Belgium
Exelixis Clinical Site #38
🇧🇪Gent, Belgium
Exelixis Clinical Site #39
🇳🇱Maastricht, Netherlands
Exelixis Clinical Site #19
🇺🇸Detroit, Michigan, United States
Exelixis Clinical Site #10
🇺🇸Detroit, Michigan, United States
Exelixis Clinical Site #4
🇺🇸Oklahoma City, Oklahoma, United States
Exelixis Clinical Site#87
🇫🇷Paris, Ile-de-France, France
Exelixis Clinical Site #48
🇺🇸Birmingham, Alabama, United States
Exelixis Clinical Site #11
🇺🇸Omaha, Nebraska, United States
Exelixis Clinical Site#86
🇰🇷Busan, Gyeongsangnam-do, Korea, Republic of
Exelixis Clinical Site#77
🇰🇷Seoul, Seoul Teugbyeolsi [Seoul-T'ukpyolshi], Korea, Republic of