Clinical trial NCT04925284: Study of XB002 in Subjects With Solid Tumors (JEWEL-101)
Official title: A Dose-Escalation and Expansion Study of the Safety and Pharmacokinetics of XB002 as Single-Agent and Combination Therapy in Subjects With Inoperable Locally Advanced or Metastatic Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Non Small Cell Lung Cancer
Cervical Cancer
SCCHN
Pancreatic Cancer
Esophageal SCC
Metastatic Castration-resistant Prostate Cancer
Triple Negative Breast Cancer
Hormone Receptor-positive Breast Cancer
Epithelial Ovarian Cancer
Endometrial Cancer
Tissue Factor-Expressing Solid Tumors
Keywords: ADC
Antibody drug conjugate
Tissue Factor
Auristatin
Nivolumab
bevacizumab
Lead sponsor: Exelixis
Sponsor class: INDUSTRY
First posted: 2021-06-14
Enrollment: 269
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Dose-escalation followed by cohort-expansion in tumor-specific expansion cohorts
Primary purpose: TREATMENT

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 or bevacizumab to subjects with advanced solid tumors.


Eligibility criteria: Inclusion Criteria:

* Cytologically or histologically and radiologically confirmed solid tumor that is inoperable, locally advanced, metastatic, or recurrent.
* Dose-Escalation Stage Cohorts A, AB, and AN: The subject has received at least 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.
* Cohort H (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.

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Dose-Escalation Stage: MTD/recommended dose for XB002
timeFrame: 18 months
measure: Cohort-Expansion Stage: Objective Response Rate (ORR)
timeFrame: 12 months
Secondary outcomes:
measure: Safety of XB002: Adverse Events
timeFrame: 30 months
measure: Tolerability of XB002 as evaluated by the duration of exposure for the study
timeFrame: 30 months
measure: Tolerability of XB002 as evaluated dose intensity of the study treatment
timeFrame: 30 months
measure: Maximum Plasma Concentration (Cmax)
timeFrame: 30 months
measure: Trough Concentration (Ctrough)
timeFrame: 30 months
measure: Immunogenicity of XB002
timeFrame: 30 months
measure: Anti-tumor activity of XB002: Objective Response Rate (ORR)
timeFrame: 30 months
measure: Anti-tumor activity of XB002: Duration of Response (DOR)
timeFrame: 30 months
measure: Anti-tumor activity of XB002: Progression Free Survival (PFS)
timeFrame: 30 months
measure: Cohort-Expansion Stage: overall survival
timeFrame: 12 months
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Exelixis Clinical Site #48
state: Alabama
city: Tucson
country: United States
facility: Exelixis Clinical Site #20
state: Arizona
city: Tucson
country: United States
facility: Exelixis Clinical Site#95
state: Arizona
city: Little Rock
country: United States
facility: Exelixis Clinical Site#58
state: Arkansas
city: Fountain Valley
country: United States
facility: Exelixis Clinical Site#59
state: California
city: Los Angeles
country: United States
facility: Exelixis Clinical Site #21
state: California
city: Los Angeles
country: United States
facility: Exelixis Clinical Site #26
state: California
city: New Haven
country: United States
facility: Exelixis Clinical Site #16
state: Connecticut
city: Washington
country: United States
facility: Exelixis Clinical Site #22
state: District of Columbia
city: Chicago
country: United States
facility: Exelixis Clinical Site#93
state: Illinois
city: Baltimore
country: United States
facility: Exelixis Clinical Site #6
state: Maryland
city: Columbia
country: United States
facility: Exelixis Clinical Site #18
state: Maryland
city: Boston
country: United States
facility: Exelixis Clinical Site #25
state: Massachusetts
city: Detroit
country: United States
facility: Exelixis Clinical Site #19
state: Michigan
city: Detroit
country: United States
facility: Exelixis Clinical Site #10
state: Michigan
city: Saint Louis
country: United States
facility: Exelixis Clinical Site #5
state: Missouri
city: Omaha
country: United States
facility: Exelixis Clinical Site #11
state: Nebraska
city: East Brunswick
country: United States
facility: Exelixis Clinical Site #8
state: New Jersey
city: New Brunswick
country: United States
facility: Exelixis Clinical Site #7
state: New Jersey
city: Albany
country: United States
facility: Exelixis Clinical Site #23
state: New York
city: Lake Success
country: United States
facility: Exelixis Clinical Site#67
state: New York
city: New York
country: United States
facility: Exelixis Clinical Site #12
state: New York
city: Cleveland
country: United States
facility: Exelixis Clinical Site #15
state: Ohio
city: Cleveland
country: United States
facility: Exelixis Clinical Site #29
state: Ohio
city: Hilliard
country: United States
facility: Exelixis Clinical Site #49
state: Ohio
city: Oklahoma City
country: United States
facility: Exelixis Clinical Site #4
state: Oklahoma
city: Nashville
country: United States
facility: Exelixis Clinical Site #3
state: Tennessee
city: Austin
country: United States
facility: Exelixis Clinical Site #24
state: Texas
city: Austin
country: United States
facility: Exelixis Clinical Site #1
state: Texas
city: Dallas
country: United States
facility: Exelixis Clinical Site #32
state: Texas
city: Dallas
country: United States
facility: Exelixis Clinical Site #14
state: Texas
city: Houston
country: United States
facility: Exelixis Clinical Site#92
state: Texas
city: San Antonio
country: United States
facility: Exelixis Clinical Site #2
state: Texas
city: Charlottesville
country: United States
facility: Exelixis Clinical Site #9
state: Virginia
city: Miranda
country: Australia
facility: Exelixis Clinical Site#75
state: New South Wales
city: Nedlands
country: Australia
facility: Exelixis Clinical Site#70
state: Western Australia
city: Darlinghurst
country: Australia
facility: Exelixis Clinical Site #37
city: Liverpool
country: Australia
facility: Exelixis Clinical Site #44
city: Saint Leonards
country: Australia
facility: Exelixis Clinical Site #35
city: Charleroi
country: Belgium
facility: Exelixis Clinical Site#71
state: Hainaut
city: Liège
country: Belgium
facility: Exelixis Clinical Site#66
state: Liege
city: Brussels
country: Belgium
facility: Exelixis Clinical Site#56
city: Brussels
country: Belgium
facility: Exelixis Clinical Site #30
city: Edegem
country: Belgium
facility: Exelixis Clinical Site #47
city: Gent
country: Belgium
facility: Exelixis Clinical Site #38
city: Paris
country: France
facility: Exelixis Clinical Site#87
state: Ile-de-France
city: Lyon
country: France
facility: Exelixis Clinical Site#69
state: Rhone-Alpes
city: Bordeaux
country: France
facility: Exelixis Clinical Site #45
city: Pierre Benite
country: France
facility: Exelixis Clinical Site #41
city: Poitiers
country: France
facility: Exelixis Clinical Site#68
city: Rennes
country: France
facility: Exelixis Clinical Site #50
city: Strasbourg
country: France
facility: Exelixis Clinical Site#63
city: Villejuif
country: France
facility: Exelixis Clinical Site#53
city: Milano
country: Italy
facility: Exelixis Clinical Site#62
state: MI
city: Ancona
country: Italy
facility: Exelixis Clinical Site #54
city: Firenze
country: Italy
facility: Exelixis Clinical Site#60
city: Milan
country: Italy
facility: Exelixis Clinical Site#84
city: Roma
country: Italy
facility: Exelixis Clinical Site #40
city: Roma
country: Italy
facility: Exelixis Clinical Site#90
city: Rozzano
country: Italy
facility: Exelixis Clinical Site #34
city: Siena
country: Italy
facility: Exelixis Clinical Site#61
city: Anyang-si
country: Korea, Republic of
facility: Exelixis Clinical Site#79
state: Gyeonggi-do
city: Seongnam-si
country: Korea, Republic of
facility: Exelixis Clinical Site#80
state: Gyeonggi-Do
city: Seongnam-si
country: Korea, Republic of
facility: Exelixis Clinical Site#74
state: Gyeonggido
city: Suwon
country: Korea, Republic of
facility: Exelixis Clinical Site#83
state: Gyeonggido
city: Busan
country: Korea, Republic of
facility: Exelixis Clinical Site#86
state: Gyeongsangnam-do
city: Hwasun
country: Korea, Republic of
facility: Exelixis Clinical Site#78
state: Jeonranamdo
city: Seoul
country: Korea, Republic of
facility: Exelixis Clinical Site#77
state: Seoul Teugbyeolsi
city: Seoul
country: Korea, Republic of
facility: Exelixis Clinical Site#94
state: Seoul Teugbyeolsi
city: Seoul
country: Korea, Republic of
facility: Exelixis Clinical Site#81
state: Seoul Teugbyeolsi
city: Seoul
country: Korea, Republic of
facility: Exelixis Clinical Site#85
state: Seoul Teugbyeolsi
city: Amsterdam
country: Netherlands
facility: Exelixis Clinical Site#73
state: Noord-Holland
city: Rotterdam
country: Netherlands
facility: Exelixis Clinical Site#76
state: Zuid-Holland
city: Groningen
country: Netherlands
facility: Exelixis Clinical Site#65
city: Maastricht
country: Netherlands
facility: Exelixis Clinical Site #39
city: Barcelona
country: Spain
facility: Exelixis Clinical Site #27
city: Barcelona
country: Spain
facility: Exelixis Clinical Site #36
city: Barcelona
country: Spain
facility: Exelixis Clinical Site#55
city: Barcelona
country: Spain
facility: Exelixis Clinical Site#82
city: Lleida
country: Spain
facility: Exelixis Clinical Site #31
city: Madrid
country: Spain
facility: Exelixis Clinical Site#64
city: Madrid
country: Spain
facility: Exelixis Clinical Site #17
city: Madrid
country: Spain
facility: Exelixis Clinical Site #33
city: Madrid
country: Spain
facility: Exelixis Clinical Site #42
city: Madrid
country: Spain
facility: Exelixis Clinical Site #13
city: Málaga
country: Spain
facility: Exelixis Clinical Site #46
city: Valencia
country: Spain
facility: Exelixis Clinical Site #43
city: Valencia
country: Spain
facility: Exelixis Clinical Site #51
city: Zaragoza
country: Spain
facility: Exelixis Clinical Site#72
city: Leicester
country: United Kingdom
facility: Exelixis Clinical Site#88
state: England
city: London
country: United Kingdom
facility: Exelixis Clinical Site#89
state: England
city: Cardiff
country: United Kingdom
facility: Exelixis Clinical Site#91
state: Wales
city: Glasgow
country: United Kingdom
facility: Exelixis Clinical Site #52
city: London
country: United Kingdom
facility: Exelixis Clinical Site#57
city: Newcastle Upon Tyne
country: United Kingdom
facility: Exelixis Clinical Site #28
Study officials:
References: