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.
Dose-Escalation Stage (Single-Agent and Combination Therapy Cohorts):
Primary Objectives:
To determine the MTD and/or RD for further evaluation of intravenous (IV) administration of XB002 alone and in combination therapy in subjects with advanced malignancies
Additional Objectives:
- To establish the preliminary safety and tolerability profile of XB002 when administered alone and in combination therapy
- To evaluate the PK of XB002 (antibody conjugated to payload), total antibody (unconjugated and conjugated antibody), and free payload following IV administration alone and in combination therapy
- To assess the immunogenicity of XB002
- To evaluate the anti-tumor activity of XB002 alone and in combination therapy as measured by objective response rate (ORR), duration of response (DOR), and progression-free survival (PFS) per RECIST 1.1 as assessed by the Investigator
Exploratory Objectives:
- To evaluate the relationship between PK and exploratory biomarkers, preliminary efficacy, and safety outcomes
Cohort-Expansion Stage (Single-Agent and Combination Therapy Cohorts):
Primary Objective:
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
Additional Objectives:
- To evaluate the safety and tolerability of XB002 when administered alone and in combination therapy
- To further evaluate the PK of XB002 (antibody conjugated to payload), total antibody (unconjugated and conjugated antibody), and free payload following IV administration alone and in combination therapy
- To assess the immunogenicity of XB002
- To evaluate the anti-tumor activity of XB002 alone and in combination therapy as
measured by DOR and PFS per RECIST 1.1 as assessed by the Investigator
- To evaluate the anti-tumor activity of XB002 alone and in combination therapy as measured by ORR, DOR, and PFS per RECIST 1.1 as assessed by a Blinded Independent Radiology Committee (BIRC) for selected cohorts
- To evaluate overall survival
- To evaluate changes in tumor markers from baseline for selected tumor indications
Exploratory Objectives:
- To assess the effects of XB002 on tumor and blood biomarkers
- To evaluate the exposure of nivolumab in combination with XB002
- To assess the immunogenicity of nivolumab in combination with XB002
- Rutgers Cancer Institute of New Jersey
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.
Please note that we have obtained the inclusion and exclusion criteria information from the National Institutes of Health’s clinical trials web site ClinicalTrials.gov. The listed criteria may not necessarily reflect recent amendments to the protocol and the current criteria.
For further information about clinical trials, please contact us at 732-235-7356.