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 Identifier:
XB002-101
CT.gov Identifier:
NCT04925284
EudraCT Identifier:
2021-006543-10
EU Trial (CTIS) Number:
2023-508267-69-00
Study Contact Information:
N/A
Study Complete

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Study Summary

To evaluate the safety, tolerability, pharmacokinetics and preliminary antitumor activity dose escalation and expansion study of ICON-2.

To evaluate the safety, tolerability, PK, pharmacodynamics, and clinical antitumor activity of XB002 administered IV q3w as a monotherapy alone and in combination with nivolumab or bevacizumab to subjects with advanced solid tumors.

To evaluate the safety, tolerability, pharmacokinetics (PK), immunogenicity (anti-drug antibodies) and preliminary antitumor activity of XB002. Presented here is the trial design.

The MTD/RD will be further evaluated in multiple tumor-specific expansion cohorts of advanced solid tumors (~30 patients per cohort) using a Simon’s 2-stage design.

To present initial results from the dose-escalation stage of the JEWEL-101 study with XB002 in advanced solid tumors.

To evaluate safety and antitumor activity in advanced solid tumors. Presented is the design of the cohort expansion stage.

To evaluate the safety, tolerability, pharmacokinetics (PK), and antitumor activity of XB002 in advanced solid tumors.

Single-agent XB002 at the recommended dose will be assessed in the BC expansion cohorts utilizing Simon’s Two-Stage design

Main objective of the trial

Cohort-Expansion Stage (Single-Agent and Combination Therapy Cohorts): Primary:

• To evaluate the preliminary efficacy of XB002 when administered alone and in combination therapy by estimating the ORR per RECIST 1.1 as assessed by the Investigator

Cohort-Expansion Stage (Single-Agent and Combination Therapy Cohorts): Primary:

• To evaluate the preliminary efficacy of XB002 when administered alone and in combination therapy by estimating the ORR per RECIST 1.1 as assessed by the Investigator

Medical Condition
The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.
  • Breast Cancers
  • Non-Small Cell Lung Cancer
  • Ovarian
  • Pancreas
  • Prostate
  • Head & Neck
  • Solid Tumor
  • Endometrial
  • Esophageal
  • Cervical cancer
  • Fallopian Tube
  • Primary Peritoneal
  • Appendix Cancer
    • Phase
    The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
    I
    Sex
    Female & Male
    Age
    18+ years
    Study Drug
  • Drug: Experimental: XB002 Single-Agent Dose-Escalation Cohorts
    • Read More
  • Drug: Experimental: XB002 + Nivolumab Dose Escalation Cohorts
  • Drug: Drug: Bevacizumab
  • Drug: AACR 2022:
  • Drug: ESMO-Asia 2023:
  • Drug: ASCO GI 2024:
  • Drug: Pts in the mCRPC cohort will be treated with XB002 single agent.
    • Study Status
    Indicates the current recruitment status or the expanded access status
    Study Complete

    Requirements information
    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.
    • Pts with mCRPC and primary histology of adenocarcinoma are eligible; neuroendocrine differentiation and other histological features are also permitted. Pts must have documented progressive disease after 1–3 prior systemic therapies, including at least 1 prior NHT for metastatic castration-sensitive or castration-resistant disease. Prior taxane-based chemotherapy is optional, and bone-only disease without soft-tissue tumor components is allowed.
    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.
    • Key exclusion criteria include prior treatment with TF-targeting or auristatin-based ADCs, and significant ocular disorders. Concomitant anticoagulants are permitted, and pts with PN are eligible, provided it is not impacting activities of daily living.
    • No prior treatment with TF-targeting or auristatin-based ADCs is allowed, and pts with significant ocular disorders are excluded.

    Clinical Study Information for Healthcare Providers

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    Study Locations

    Location
    Investigator
    Status
    Condition(s) Treated at Site
    Location
    START Madrid, Spain (CIOCC)
    Madrid, Spain, 28050
    Investigator
    Maria de Miguel
    Status
    Recruitment Complete
    Condition(s) Treated at Site
    Breast Cancers
    Non-Small Cell Lung Cancer
    Ovarian
    Pancreas
    Prostate
    Head & Neck
    Solid Tumor
    Endometrial
    Esophageal
    Cervical cancer
    Fallopian Tube
    Primary Peritoneal
    Appendix Cancer