All Drugs and Chemicals

Coagulants

Antibodies

Immunoglobulins

Thromboplastin

All patients in Part A (dose escalation) and Part B (dose expansion) will be administrated MRG004A on Day 1 of every 3 weeks (21-day cycle).

MRG004A

Jenny Li

Leanne Drummond, Bachelor

Carmen Lu

Amin Yaqubie

Nashat Y Gabrail, MD

Carrie Smith

Abby Reed

Christine Nocera

Marcy Sullivan, RN, BSN, OCN

Jie Tang, M.D.

Jian Zhang, M.D

Xiaohua Wu, M.D

Jianzhen Shan, M.D.

The objective of this study is to evaluate the safety, efficacy, pharmacokinetics, and immunogenicity of MRG004A in patients with Tissue Factor positive advanced or metastatic solid tumors.

This study consists of two parts. Part A is a dose escalation study to determine the maximum tolerated dose (MTD) and recommended phase II dose (RP2D) of MRG004A. Part B is a disease specific multi-cohort dose expansion study to further assess the efficacy and safety of MRG004A at confirmed RP2D.

A Study of MRG004A in Patients With Tissue Factor Positive Advanced or Metastatic Solid Tumors

An Open-Label, Multi-center, Phase I/II Dose Escalation and Expansion Study to Assess the Safety, Tolerability, Anti-Tumor Activity and Pharmacokinetics of MRG004A in Patients With Tissue Factor Positive Advanced or Metastatic Solid Tumors

The highest dose confirmed wherein less than 2 out of 6, or \< 33% of evaluable patients in a treatment cohort experiences dose-limiting toxicity (DLT).

The dose level of MRG004A recommended for further clinical studies based on assessment of the safety, efficacy and PK data from Part A of this study.

The proportion of patients who achieve complete response (CR) or partial response (PR) as assessed by the Independent Central Review (ICR).

Any reaction, side effect, or untoward event that occurs during the course of the clinical trial whether or not the event is considered related to the study drug.

The time interval between the date of the earliest qualifying response and the date of disease progression or death for any cause, whichever occurs earlier.

The proportion of patients who achieve CR, PR, or stable disease (SD) ≥ 6 weeks based on RECIST v1.1.

The time from the date of first study dose to disease progression or death whichever occurs first.

The time from start of study treatment to date of death as a result of any cause.

Time to reach the maximum plasma concentration.

Area under the plasma concentration-time curve from time 0 to the time of last quantifiable concentration.

The proportion of patients with positive ADA immunogenicity results.

Shanghai Miracogen Inc.

Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Skin and Connective Tissue Diseases

Digestive System Diseases

Gland and Hormone Related Diseases

Rare Diseases

Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

Prostatic Neoplasms

Breast Neoplasms

Triple Negative Breast Neoplasms

Pancreatic Neoplasms

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Uterine Cervical Neoplasms

Esophageal Squamous Cell Carcinoma

Endometrial Neoplasms

Carcinoma

Breast Diseases

Skin Diseases

Urogenital Neoplasms

Genital Diseases

Urogenital Diseases

Endocrine Gland Neoplasms

Endocrine System Diseases

Ovarian Diseases

Adnexal Diseases

Genital Diseases, Female

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Genital Neoplasms, Female

Gonadal Disorders

Uterine Neoplasms

Uterine Diseases

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Pancreatic Cancer

Ovarian Cancer

Ovarian Epithelial Cancer

Antineoplastic Agents

Hormones

Nivolumab

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Subjects (Cohort A) will accrue in cohorts of 3-12 subjects in a modified i3+3 design.

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), epithelial 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).

Subjects (Cohort AN) will accrue in cohorts of 3-12 subjects in a modified i3+3 design.

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).

XB002

Exelixis Clinical Trials

Backup or International

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.

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

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

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

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

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 Cmax for XB002, total antibody, and free payload at scheduled visits over time

To evaluate the Ctrough of XB002, total antibody, and free payload at scheduled visits over time

To assess the immunogenicity of XB002 as measured by anti-drug antibody (ADA) analysis

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).

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)

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)

Exelixis

Heart and Blood Diseases

Head and Neck Neoplasms

Sarcoma

Thromboembolism

Venous Thromboembolism

Soft Tissue Sarcoma

Herbal and Botanical

Gemcitabine

Antimetabolites

Cola

Study participants will receive up to four courses of a 28-day biochemotherapy with the study drug (ALT-836) and gemcitabine. Each treatment course consists of five doses of ALT-836 (on Day 1, 4, 8, 15 and 22) and three doses of gemcitabine (Day 1, 8 and 15). Participants with persistent responses will receive additional two cycles, three doses each, of standard of care gemcitabine therapy.

ALT-836 in combination with gemcitabine

This is a Phase I, open-label, multi-center, competitive enrollment and dose-escalation study of ALT-836 in combination with standard of care gemcitabine in participants who have locally advanced or metastatic solid tumors. The purpose of this study is to determine the maximum tolerated dose (MTD), and to assess the safety and pharmacokinetic profile of ALT-836 given with gemcitabine. The clinical benefit, progression-free survival and overall survival of study participants will also be assessed.

Tissue Factor (TF) is over-expressed in most cancer types. Results from many recent studies have suggested a key role for TF in the development of cancer-associated thrombosis, tumor growth, tumor angiogenesis, and tumor metastasis. ALT-836, a recombinant human-chimeric monoclonal antibody, is designed as a direct TF antagonist to block TF displayed by cancers and to inhibit cancer-associated venous thromboembolism, tumor growth, tumor angiogenesis and tumor metastasis. In numerous pre-clinical studies in laboratory animals, including non-human primates, ALT-836 exhibits potent anti-tumor, anti-thrombotic and anti-inflammatory activities with a remarkable safety profile. In humans, ALT-836, administered as a single bolus and monotherapy in patients with coronary artery disease (CAD) and acute lung injury/acute respiratory distress syndrome (ALI/ARDS), is safe and exhibits anti-coagulant and anti-inflammatory effects. A Phase II study using a multi-dose regimen of ALT-836 is being conducted in patients with ALI/ARDS. In the dose-escalation study described in this protocol, the investigators will assess the safety and determine the maximum tolerated dose (MTD) of ALT-836 in combination with gemcitabine in patients with advanced malignancies known to overexpress TF and in which venous thromboembolism is a major complication.

A Study of ALT-836 in Combination With Gemcitabine for Locally Advanced or Metastatic Solid Tumors

A Phase I, Open-Label, Multi-center, Competitive Enrollment and Dose-escalation Study of ALT-836 in Combination With Gemcitabine for Locally Advanced or Metastatic Solid Tumors

Number and severity of treatment related AEs that occur or worsen after the first dose of study treatment

Number of participants with complete response, partial response or stable disease

Number of participants with 9-month, 12-month, 18-month, 24-month, 30-month or 36-month progression-free survival

Number of participants with 9-month, 12-month, 18-month, 24-month, 30-month or 36-month overall survival

Area under the plasma concentration-time curve from time zero to infinity (AUC) and the half-life of ALT-836

Altor BioScience

Symptoms and General Pathology

Nervous System Diseases

Body Weight

Glioma

Brain Neoplasms

Disease Progression

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms, Nerve Tissue

Central Nervous System Neoplasms

Nervous System Neoplasms

Brain Diseases

Central Nervous System Diseases

Thrombosis

Embolism

Embolism and Thrombosis

Vascular Diseases

Neuroepithelioma

Fibrinolytic Agents

Anticoagulants

Heparin

Calcium heparin

Heparin, Low-Molecular-Weight

Tinzaparin

Dalteparin

Agnes Lee, MD

William Geerts, MD

Mark Levine, MD

James Perry, MD

Janusz Rak

Jeffrey Weitz, MD

To explore the relationship between tissue factor levels, tumour progression, activation of blood coagulation and venous thromboembolism with malignant glioma

The Roles of Tissue Factor in Malignant Gliomas

Ontario Cancer Research Network

Ontario Clinical Oncology Group (OCOG)

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Chong-Jen Yu, M.D., Ph.D.

This study uses serum tissue factor and tissue factor inhibitor and factor VII to monitor the pre-coagulation status in lung cancer patients and to correlate the pre-coagulation status with clinical staging and prognosis.

The staging of lung cancer was according to tumor size, involvement of lymph node and metastatic status. But there is a different prognosis in cancer patients of the same stage. The coagulation status of cancer patients was considered as an important possible prognostic factor. So in this study, we want to evaluate patients' coagulation status and find the relation of coagulation status and cancer status.

We thus propose a prospective study using coagulation factors in order to search for the relationship between cancer stage and pre-coagulation status in Taiwanese lung cancer patients. We will also evaluate the potential use of tissue factor as a prognosis predictor in lung cancer patients.

The Serum Tissue Factor Level in Lung Cancer Patients as a Prognostic Factor

National Taiwan University Hospital

Adenocarcinoma

Neoplasm Metastasis

Colonic Neoplasms

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Micronutrients

Leucovorin

Fluorouracil

Protein C

recombinant nematode anticoagulant protein c2 (rNAPc2)

Ted Love, MD

This is a multicenter, two-stage trial with the goal of evaluating up to 100 subjects. This trial will be performed to initiate identification of a safe and effective dose of twice-weekly, subcutaneous rNAPc2 for the second-line treatment of metastatic colorectal carcinoma in combination with contemporary 5-FU-based chemotherapy.

Cytotoxic chemotherapy combining 5-fluorouracil and leucovorin with irinotecan (FOLFIRI) or oxaliplatin (FOLFOX) or, more recently, treatment with XELOX (Roche) (capecitabine + oxaliplatin) has been the main approach for the treatment of metastatic colorectal carcinoma (mCRC), but with the advent of targeted therapies, biologic treatments are becoming an area of intense interest. Tissue factor (TF) is a transmembrane glycoprotein expressed by upwards of 85% of mCRCs.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Study of MRG004A in Patients With Tissue Factor Positive Advanced or Metastatic Solid Tumors	NCT04843709	Advanced or Met...	MRG004A	18 Years -	Shanghai Miracogen Inc.
Study of XB002 in Subjects With Solid Tumors (JEWEL-101)	NCT04925284	Non Small Cell ... Cervical Cancer SCCHN Pancreatic Canc... Esophageal SCC Metastatic Cast... Triple Negative... Hormone Recepto... Epithelial Ovar... Endometrial Can... Tissue Factor-E...	XB002 Nivolumab	18 Years -	Exelixis
A Study of ALT-836 in Combination With Gemcitabine for Locally Advanced or Metastatic Solid Tumors	NCT01325558	Locally Advance... Malignant Solid...	ALT-836 in comb...	18 Years -	Altor BioScience
The Roles of Tissue Factor in Malignant Gliomas	NCT00201903	Venous Thromboe... Brain Tumors		18 Years -	Ontario Clinical Oncology Group (OCOG)
The Serum Tissue Factor Level in Lung Cancer Patients as a Prognostic Factor	NCT00257179	Lung Cancer		16 Years -	National Taiwan University Hospital
Safety Study of Recombinant NAPc2 to Prevent Tumor Progression and Metastases in Metastatic Colon Cancer	NCT00443573	Colon Cancer	recombinant nem...	18 Years - 75 Years	ARCA Biopharma, Inc.

Spots Global Cancer Trial Database for tissue factor