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

Sponsor

Exelixis (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04925284

Collaborator

(none)

451

Enrollment

Locations

Arms

Anticipated Duration (Months)

90.2

Patients Per Site

2.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a Phase 1, non-randomized, 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.

Condition or Disease	Intervention/Treatment	Phase
Non Small Cell Lung Cancer Urothelial Cancer Ovarian Cancer Cervical Cancer SCCHN Pancreatic Cancer Esophageal SCC Metastatic Castration-resistant Prostate Cancer Triple Negative Breast Cancer Hormone Receptor-positive Breast Cancer	Drug: XB002 Drug: Nivolumab	Phase 1

Study Design

Study Type:

Interventional

Anticipated Enrollment :

451 participants

Allocation:

Non-Randomized

Intervention Model:

Sequential Assignment

Intervention Model Description:

Dose-escalation followed by cohort-expansion in tumor-specific expansion cohortsDose-escalation followed by cohort-expansion in tumor-specific expansion cohorts

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Jun 7, 2021

Anticipated Primary Completion Date :

Jun 7, 2024

Anticipated Study Completion Date :

Oct 7, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: XB002 Single-Agent Dose-Escalation Cohorts Subjects (Cohort A) will accrue in cohorts of 3-12 subjects in a modified i3+3 design.	Drug: XB002 IV administration of XB002
Experimental: XB002 Single-Agent Expansion Cohorts 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), urothelial cancer (Cohort C), 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) and hormone-receptor positive breast cancer (Cohort K).	Drug: XB002 IV administration of XB002
Experimental: XB002 + Nivolumab Dose Escalation Cohorts Subjects (Cohort AN) accrue in cohorts of 3-12 subjects in a modified i3+3 design.	Drug: XB002 IV administration of XB002 Drug: Nivolumab IV administration of Nivolumab
Experimental: XB002 + Nivolumab Dose Expansion Cohorts 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).	Drug: XB002 IV administration of XB002 Drug: Nivolumab IV administration of Nivolumab

Outcome Measures

Primary Outcome Measures

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 in subjects with advanced malignancies
Cohort-Expansion Stage: Objective Response Rate (ORR) [12 months]
To evaluate preliminary efficacy of XB002 by estimating the ORR per RECIST 1.1 as assessed by the Investigator

Secondary Outcome Measures

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)
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
Maximum Plasma Concentration (Cmax) [30 months]
To evaluate the Cmax for XB002, total antibody, and free payload at scheduled visits over time
Trough Concentration (Ctrough) [30 months]
To evaluate the Ctrough of XB002, total antibody, and free payload at scheduled visits over time
Immunogenicity of XB002 [30 months]
To assess the immunogenicity of XB002 as measured by anti-drug antibody (ADA) analysis
Dose-Escalation Stage: 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 as assessed by the Investigator
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 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 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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Cytologically or histologically and radiologically confirmed solid tumor that is inoperable, locally advanced, metastatic, or recurrent.
Dose-Escalation Stage Cohort A and AN and Cohort-Expansion Stage (Cohorts B - K, 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 C (Urothelial Cancer): Subjects with transitional cell histology (including renal pelvis, ureter, urinary bladder, urethra) who have documented radiographic disease progression during or following their last systemic anticancer therapy.
Cohort-Expansion Stage Cohort D (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.
Cohort 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 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.
Expansion Cohorts: Subjects must have measurable disease per RECIST 1.1 as determined by the Investigator.
Tumor tissue material collected approximately 2 years prior to consent. If archival tumor tissue is not available, a fresh tumor biopsy may be collected from subjects enrolled in the Dose-Escalation Stage and must be collected from subjects in the Cohort-Expansion Stage, at least 7 days (and up to 60 days) prior to first dose.
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.
Diagnosis of another malignancy within 2 years before first dose of study treatment, except for superficial skin cancers, or localized, low grade tumors deemed cured and not treated with systemic therapy.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Site 5	Saint Louis	Missouri	United States	63110
2	Site 4	Oklahoma City	Oklahoma	United States	73104
3	Site 3	Nashville	Tennessee	United States	37203
4	Site 1	Austin	Texas	United States	78758
5	Site 2	San Antonio	Texas	United States	78229