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

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

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.

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

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), 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).

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).

The MTD or recommended dose from the dose-escalation stage may be further explored in subjects with epithelial ovarian cancer [EOC] (Cohort DB)

To determine the MTD and/or RD for further evaluation of IV administration of XB002 in subjects with advanced malignancies

To evaluate preliminary efficacy of XB002 by estimating the ORR per RECIST 1.1 as assessed by the Investigator

To evaluate the safety of XB002 through the evaluation of incidence and severity of nonserious adverse events (AEs) and serious adverse events (SAEs)

To evaluate the tolerability of XB002 through the evaluation of duration of exposure for the study treatment

To evaluate the tolerability of XB002 through the evaluation of dose intensity of the study treatment

To evaluate the anti-tumor activity of XB002, as measured by ORR, per RECIST 1.1 as assessed by the Investigator

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)

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)

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 and Cohort-Expansion Stage (Cohorts B - M, BN, DB, 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 Cohorts D and DB (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 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. 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 non-melanoma cancers, or localized, low grade tumors deemed cured and not treated with systemic therapy.