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

Pancreatic Cancer Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04925284
• Other study ID #: XB002-101
• Status: Recruiting
• Phase: Phase 1
• Start date: June 7, 2021
• Est. completion date: October 7, 2024

Study information

• Verified date: February 2024
• Source: Exelixis
• Contact: Exelixis Clinical Trials
• Phone: 1-888-EXELIXIS (888-393-5494)
• Email: druginfo[@]exelixis.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 573
• Est. completion date: October 7, 2024
• Est. primary completion date: June 7, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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.

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.

Related Conditions & MeSH terms

• Breast Neoplasms
• Carcinoma, Ovarian Epithelial
• Cervical Cancer
• Endometrial Cancer
• Endometrial Neoplasms
• Epithelial Ovarian Cancer
• Esophageal SCC
• Hormone Receptor-positive Breast Cancer
• Metastatic Castration-resistant Prostate Cancer
• Non Small Cell Lung Cancer
• Pancreatic Cancer
• SCCHN
• Triple Negative Breast Cancer
• Triple Negative Breast Neoplasms

Intervention

Drug:
• XB002
IV administration of XB002
• Nivolumab
IV administration of Nivolumab

Locations

Country	Name	City	State
Australia	Exelixis Clinical Site #37	Darlinghurst
Australia	Exelixis Clinical Site #44	Liverpool
Australia	Exelixis Clinical Site#75	Miranda	New South Wales
Australia	Exelixis Clinical Site#70	Nedlands	Western Australia
Australia	Exelixis Clinical Site #35	Saint Leonards
Belgium	Exelixis Clinical Site #30	Brussels
Belgium	Exelixis Clinical Site#56	Brussels
Belgium	Exelixis Clinical Site#71	Charleroi	Hainaut
Belgium	Exelixis Clinical Site #47	Edegem
Belgium	Exelixis Clinical Site #38	Gent
Belgium	Exelixis Clinical Site#66	Liège	Liege
France	Exelixis Clinical Site #45	Bordeaux
France	Exelixis Clinical Site#69	Lyon	Rhone-Alpes
France	Exelixis Clinical Site#87	Paris	Ile-de-France
France	Exelixis Clinical Site #41	Pierre Benite
France	Exelixis Clinical Site#68	Poitiers
France	Exelixis Clinical Site #50	Rennes
France	Exelixis Clinical Site#63	Strasbourg
France	Exelixis Clinical Site#53	Villejuif
Italy	Exelixis Clinical Site #54	Ancona
Italy	Exelixis Clinical Site#60	Firenze
Italy	Exelixis Clinical Site#84	Milan
Italy	Exelixis Clinical Site#62	Milano	MI
Italy	Exelixis Clinical Site #40	Roma
Italy	Exelixis Clinical Site#90	Roma
Italy	Exelixis Clinical Site #34	Rozzano
Italy	Exelixis Clinical Site#61	Siena
Korea, Republic of	Exelixis Clinical Site#79	Anyang-si	Gyeonggi-do
Korea, Republic of	Exelixis Clinical Site#86	Busan	Gyeongsangnam-do
Korea, Republic of	Exelixis Clinical Site#78	Hwasun	Jeonranamdo [Chollanam-do]
Korea, Republic of	Exelixis Clinical Site#74	Seongnam-si	Gyeonggido [Kyonggi-do]
Korea, Republic of	Exelixis Clinical Site#80	Seongnam-si	Gyeonggi-Do
Korea, Republic of	Exelixis Clinical Site#77	Seoul	Seoul Teugbyeolsi [Seoul-T'ukpyolshi]
Korea, Republic of	Exelixis Clinical Site#81	Seoul	Seoul Teugbyeolsi [Seoul-T'ukpyolshi]
Korea, Republic of	Exelixis Clinical Site#85	Seoul	Seoul Teugbyeolsi [Seoul-T'ukpyolshi]
Korea, Republic of	Exelixis Clinical Site#83	Suwon	Gyeonggido [Kyonggi-do]
Netherlands	Exelixis Clinical Site#73	Amsterdam	Noord-Holland
Netherlands	Exelixis Clinical Site#65	Groningen
Netherlands	Exelixis Clinical Site #39	Maastricht
Netherlands	Exelixis Clinical Site#76	Rotterdam	Zuid-Holland
Spain	Exelixis Clinical Site #27	Barcelona
Spain	Exelixis Clinical Site #36	Barcelona
Spain	Exelixis Clinical Site#55	Barcelona
Spain	Exelixis Clinical Site#82	Barcelona
Spain	Exelixis Clinical Site #31	Lleida
Spain	Exelixis Clinical Site #13	Madrid
Spain	Exelixis Clinical Site #17	Madrid
Spain	Exelixis Clinical Site #33	Madrid
Spain	Exelixis Clinical Site #42	Madrid
Spain	Exelixis Clinical Site#64	Madrid
Spain	Exelixis Clinical Site #46	Málaga
Spain	Exelixis Clinical Site #43	Valencia
Spain	Exelixis Clinical Site #51	Valencia
Spain	Exelixis Clinical Site#72	Zaragoza
United Kingdom	Exelixis Clinical Site#91	Cardiff	Wales
United Kingdom	Exelixis Clinical Site #52	Glasgow
United Kingdom	Exelixis Clinical Site#88	Leicester	England
United Kingdom	Exelixis Clinical Site#57	London
United Kingdom	Exelixis Clinical Site#89	London	England
United Kingdom	Exelixis Clinical Site #28	Newcastle Upon Tyne
United States	Exelixis Clinical Site #23	Albany	New York
United States	Exelixis Clinical Site #1	Austin	Texas
United States	Exelixis Clinical Site #24	Austin	Texas
United States	Exelixis Clinical Site #6	Baltimore	Maryland
United States	Exelixis Clinical Site #48	Birmingham	Alabama
United States	Exelixis Clinical Site #25	Boston	Massachusetts
United States	Exelixis Clinical Site #9	Charlottesville	Virginia
United States	Exelixis Clinical Site #15	Cleveland	Ohio
United States	Exelixis Clinical Site #29	Cleveland	Ohio
United States	Exelixis Clinical Site #18	Columbia	Maryland
United States	Exelixis Clinical Site #14	Dallas	Texas
United States	Exelixis Clinical Site #32	Dallas	Texas
United States	Exelixis Clinical Site #10	Detroit	Michigan
United States	Exelixis Clinical Site #19	Detroit	Michigan
United States	Exelixis Clinical Site #8	East Brunswick	New Jersey
United States	Exelixis Clinical Site#59	Fountain Valley	California
United States	Exelixis Clinical Site #49	Hilliard	Ohio
United States	Exelixis Clinical Site#92	Houston	Texas
United States	Exelixis Clinical Site#67	Lake Success	New York
United States	Exelixis Clinical Site#58	Little Rock	Arkansas
United States	Exelixis Clinical Site #21	Los Angeles	California
United States	Exelixis Clinical Site #26	Los Angeles	California
United States	Exelixis Clinical Site #3	Nashville	Tennessee
United States	Exelixis Clinical Site #7	New Brunswick	New Jersey
United States	Exelixis Clinical Site #16	New Haven	Connecticut
United States	Exelixis Clinical Site #12	New York	New York
United States	Exelixis Clinical Site #4	Oklahoma City	Oklahoma
United States	Exelixis Clinical Site #11	Omaha	Nebraska
United States	Exelixis Clinical Site #5	Saint Louis	Missouri
United States	Exelixis Clinical Site #2	San Antonio	Texas
United States	Exelixis Clinical Site #20	Tucson	Arizona
United States	Exelixis Clinical Site #22	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Exelixis

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  France,  Italy,  Korea, Republic of,  Netherlands,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	Safety of XB002: Adverse Events	To evaluate the safety of XB002 through the evaluation of incidence and severity of nonserious adverse events (AEs) and serious adverse events (SAEs)	30 months
Secondary	Tolerability of XB002 as evaluated by the duration of exposure for the study	To evaluate the tolerability of XB002 through the evaluation of duration of exposure for the study treatment	30 months
Secondary	Tolerability of XB002 as evaluated dose intensity of the study treatment	To evaluate the tolerability of XB002 through the evaluation of dose intensity of the study treatment	30 months
Secondary	Maximum Plasma Concentration (Cmax)	To evaluate the Cmax for XB002, total antibody, and free payload at scheduled visits over time	30 months
Secondary	Trough Concentration (Ctrough)	To evaluate the Ctrough of XB002, total antibody, and free payload at scheduled visits over time	30 months
Secondary	Immunogenicity of XB002	To assess the immunogenicity of XB002 as measured by anti-drug antibody (ADA) analysis	30 months
Secondary	Anti-tumor activity of XB002: Objective Response Rate (ORR)	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).	30 months
Secondary	Anti-tumor activity of XB002: Duration of Response (DOR)	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)	30 months
Secondary	Anti-tumor activity of XB002: Progression Free Survival (PFS)	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)	30 months
Secondary	Cohort-Expansion Stage: overall survival	To evaluate overall survival	12 months