Study of XB002 in Subjects With Solid Tumors (JEWEL-101)

NCT04925284 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: XB002-101
• Study Type: interventional
• Target: 269
• Locations: 9 countries
• Sites: 95

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.

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

Outcome Measures

Primary Outcomes (2)

• Dose-Escalation Stage: MTD/recommended dose for XB002

  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

  18 months

• Cohort-Expansion Stage: Objective Response Rate (ORR)

  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

  12 months

Secondary Outcomes (10)

• Safety of XB002: Adverse Events

  30 months

• Tolerability of XB002 as evaluated by the duration of exposure for the study

  30 months

• Tolerability of XB002 as evaluated dose intensity of the study treatment

  30 months

• Maximum Plasma Concentration (Cmax)

  30 months

• Trough Concentration (Ctrough)

  30 months

Study Arms (5)

XB002 Single-Agent Dose-Escalation Cohorts

EXPERIMENTAL

Subjects (Cohort A) will accrue in cohorts of 3-12 subjects in a modified i3+3 design.

Drug: XB002

XB002 Single-Agent Expansion Cohorts

EXPERIMENTAL

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).

Drug: XB002

XB002 + Nivolumab Dose Escalation Cohorts

EXPERIMENTAL

Subjects (Cohort AN) will accrue in cohorts of 3-12 subjects in a modified i3+3 design.

Drug: XB002; Drug: Nivolumab

XB002 + Nivolumab Dose Expansion Cohorts

EXPERIMENTAL

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).

Drug: XB002; Drug: Nivolumab

Experimental: XB002 + Bevacizumab Dose Escalation Cohorts

EXPERIMENTAL

Subjects (Cohort AB) will accrue in cohorts of 3-12 subjects in a modified i3+3 design.

Drug: XB002; Drug: Bevacizumab

Interventions

XB002 DRUG

IV administration of XB002

Experimental: XB002 + Bevacizumab Dose Escalation Cohorts; XB002 + Nivolumab Dose Escalation Cohorts; XB002 + Nivolumab Dose Expansion Cohorts; XB002 Single-Agent Dose-Escalation Cohorts; XB002 Single-Agent Expansion Cohorts

Nivolumab DRUG

IV administration of Nivolumab

XB002 + Nivolumab Dose Escalation Cohorts; XB002 + Nivolumab Dose Expansion Cohorts

Bevacizumab DRUG

IV administration of bevacizumab

Experimental: XB002 + Bevacizumab Dose Escalation Cohorts

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Exelixis: lead

Study Sites (95)

Exelixis Clinical Site #48

Birmingham, Alabama, 35294, United States

Location

Exelixis Clinical Site #20

Tucson, Arizona, 85704, United States

Location

Exelixis Clinical Site#95

Tucson, Arizona, 85719, United States

Location

Exelixis Clinical Site#58

Little Rock, Arkansas, 72205, United States

Location

Exelixis Clinical Site#59

Fountain Valley, California, 92708, United States

Location

Exelixis Clinical Site #21

Los Angeles, California, 90025, United States

Location

Exelixis Clinical Site #26

Los Angeles, California, 90404, United States

Location

Exelixis Clinical Site #16

New Haven, Connecticut, 06511, United States

Location

Exelixis Clinical Site #22

Washington D.C., District of Columbia, 20007, United States

Location

Exelixis Clinical Site#93

Chicago, Illinois, 60637, United States

Location

Exelixis Clinical Site #6

Baltimore, Maryland, 21287, United States

Location

Exelixis Clinical Site #18

Columbia, Maryland, 21044, United States

Location

Exelixis Clinical Site #25

Boston, Massachusetts, 02215, United States

Location

Exelixis Clinical Site #19

Detroit, Michigan, 48202, United States

Location

Exelixis Clinical Site #10

Detroit, Michigan, 49201, United States

Location

Exelixis Clinical Site #5

St Louis, Missouri, 63110, United States

Location

Exelixis Clinical Site #11

Omaha, Nebraska, 68130, United States

Location

Exelixis Clinical Site #8

East Brunswick, New Jersey, 08816, United States

Location

Exelixis Clinical Site #7

New Brunswick, New Jersey, 08903, United States

Location

Exelixis Clinical Site #23

Albany, New York, 12206, United States

Location

Exelixis Clinical Site#67

Lake Success, New York, 11042, United States

Location

Exelixis Clinical Site #12

New York, New York, 10016, United States

Location

Exelixis Clinical Site #15

Cleveland, Ohio, 44106, United States

Location

Exelixis Clinical Site #29

Cleveland, Ohio, 44195, United States

Location

Exelixis Clinical Site #49

Hilliard, Ohio, 43026, United States

Location

Exelixis Clinical Site #4

Oklahoma City, Oklahoma, 73104, United States

Location

Exelixis Clinical Site #3

Nashville, Tennessee, 37203, United States

Location

Exelixis Clinical Site #24

Austin, Texas, 78705, United States

Location

Exelixis Clinical Site #1

Austin, Texas, 78758, United States

Location

Exelixis Clinical Site #32

Dallas, Texas, 75246, United States

Location

Exelixis Clinical Site #14

Dallas, Texas, 75390, United States

Location

Exelixis Clinical Site#92

Houston, Texas, 77030, United States

Location

Exelixis Clinical Site #2

San Antonio, Texas, 78229, United States

Location

Exelixis Clinical Site #9

Charlottesville, Virginia, 22903, United States

Location

Exelixis Clinical Site#75

Miranda, New South Wales, 2228, Australia

Location

Exelixis Clinical Site#70

Nedlands, Western Australia, 6009, Australia

Location

Exelixis Clinical Site #37

Darlinghurst, 2010, Australia

Location

Exelixis Clinical Site #44

Liverpool, 2170, Australia

Location

Exelixis Clinical Site #35

Saint Leonards, 2065, Australia

Location

Exelixis Clinical Site#71

Charleroi, Hainaut, 6000, Belgium

Location

Exelixis Clinical Site#66

Liège, Liege, 4000, Belgium

Location

Exelixis Clinical Site#56

Brussels, 1070, Belgium

Location

Exelixis Clinical Site #30

Brussels, 1200, Belgium

Location

Exelixis Clinical Site #47

Edegem, 2650, Belgium

Location

Exelixis Clinical Site #38

Ghent, 9000, Belgium

Location

Exelixis Clinical Site#69

Lyon, Auvergne-Rhône-Alpes, 69373, France

Location

Exelixis Clinical Site #45

Bordeaux, 33000, France

Location

Exelixis Clinical Site #41

Pierre-Bénite, 69310, France

Location

Exelixis Clinical Site#68

Poitiers, 86000, France

Location

Exelixis Clinical Site #50

Rennes, 35042, France

Location

Exelixis Clinical Site#63

Strasbourg, 67200, France

Location

Exelixis Clinical Site#53

Villejuif, 94805, France

Location

Exelixis Clinical Site#87

Paris, Île-de-France Region, 75013, France

Location

Exelixis Clinical Site#62

Milan, MI, 20141, Italy

Location

Exelixis Clinical Site #54

Ancona, 60126, Italy

Location

Exelixis Clinical Site#60

Florence, 50134, Italy

Location

Exelixis Clinical Site#84

Milan, 20132, Italy

Location

Exelixis Clinical Site #40

Roma, 00144, Italy

Location

Exelixis Clinical Site#90

Roma, 00168, Italy

Location

Exelixis Clinical Site #34

Rozzano, 20089, Italy

Location

Exelixis Clinical Site#61

Siena, 53100, Italy

Location

Exelixis Clinical Site#73

Amsterdam, North Holland, 1066 CX, Netherlands

Location

Exelixis Clinical Site#76

Rotterdam, South Holland, 3015 GD, Netherlands

Location

Exelixis Clinical Site#65

Groningen, 9713 GZ, Netherlands

Location

Exelixis Clinical Site #39

Maastricht, 6229 HX, Netherlands

Location

Exelixis Clinical Site#79

Anyang-si, Gyeonggi-do, 14068, South Korea

Location

Exelixis Clinical Site#80

Seongnam-si, Gyeonggi-do, 13496, South Korea

Location

Exelixis Clinical Site#74

Seongnam-si, Gyeonggido, 13620, South Korea

Location

Exelixis Clinical Site#83

Suwon, Gyeonggido, 16247, South Korea

Location

Exelixis Clinical Site#86

Pusan, Gyeongsangnam-do, 49201, South Korea

Location

Exelixis Clinical Site#78

Hwasun, Jeonranamdo, 58128, South Korea

Location

Exelixis Clinical Site#77

Seoul, Seoul Teugbyeolsi, 02841, South Korea

Location

Exelixis Clinical Site#94

Seoul, Seoul Teugbyeolsi, 05505, South Korea

Location

Exelixis Clinical Site#81

Seoul, Seoul Teugbyeolsi, 06351, South Korea

Location

Exelixis Clinical Site#85

Seoul, Seoul Teugbyeolsi, 6591, South Korea

Location

Exelixis Clinical Site #27

Barcelona, 08023, Spain

Location

Exelixis Clinical Site #36

Barcelona, 08028, Spain

Location

Exelixis Clinical Site#55

Barcelona, 8035, Spain

Location

Exelixis Clinical Site#82

Barcelona, 8908, Spain

Location

Exelixis Clinical Site #31

Lleida, 25198, Spain

Location

Exelixis Clinical Site#64

Madrid, 1217, Spain

Location

Exelixis Clinical Site #17

Madrid, 28027, Spain

Location

Exelixis Clinical Site #33

Madrid, 28040, Spain

Location

Exelixis Clinical Site #42

Madrid, 28050, Spain

Location

Exelixis Clinical Site #13

Madrid, 28223, Spain

Location

Exelixis Clinical Site #46

Málaga, 29010, Spain

Location

Exelixis Clinical Site #43

Valencia, 46010, Spain

Location

Exelixis Clinical Site #51

Valencia, 46026, Spain

Location

Exelixis Clinical Site#72

Zaragoza, 50009, Spain

Location

Exelixis Clinical Site#88

Leicester, England, LE1 5WW, United Kingdom

Location

Exelixis Clinical Site#89

London, England, SE1 9RT, United Kingdom

Location

Exelixis Clinical Site#91

Cardiff, Wales, CF14 2TL, United Kingdom

Location

Exelixis Clinical Site #52

Glasgow, G12 0YN, United Kingdom

Location

Exelixis Clinical Site#57

London, W1T 7HA, United Kingdom

Location

Exelixis Clinical Site #28

Newcastle upon Tyne, NE7 7DN, United Kingdom

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Uterine Cervical Neoplasms; Pancreatic Neoplasms; Esophageal Squamous Cell Carcinoma; Triple Negative Breast Neoplasms; Carcinoma, Ovarian Epithelial; Endometrial Neoplasms

Interventions

Nivolumab; Bevacizumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases; Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms, Squamous Cell; Esophageal Neoplasms; Gastrointestinal Neoplasms; Head and Neck Neoplasms; Esophageal Diseases; Gastrointestinal Diseases; Breast Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Ovarian Neoplasms; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Dose-escalation followed by cohort-expansion in tumor-specific expansion cohorts

Study Record Dates

• First Submitted: May 27, 2021
• First Posted: June 14, 2021
• Study Start: June 7, 2021
• Primary Completion: March 10, 2025
• Study Completion: March 10, 2025
• Last Updated: April 4, 2025

Record last verified: 2025-04

Locations

KR (10); ES (14); AU (5); US (34); IT (8); GB (6); BE (6); FR (8); NL (4)