Neoplasms

All Conditions

Digestive System Diseases

Gland and Hormone Related Diseases

Heart and Blood Diseases

Rare Diseases

Adenocarcinoma

Pancreatic Neoplasms

Thromboembolism

Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Pancreatic Cancer

Antineoplastic Agents

All Drugs and Chemicals

Anticoagulants

Gemcitabine

Paclitaxel

Albumin-Bound Paclitaxel

Rivaroxaban

Tubulin Modulators

Antimitotic Agents

Antimetabolites

Patients without a prior TE will be treated with prophylactic dose and schedule of rivaroxaban (10 mg QD), together with standard dose and schedule of gemcitabine, nab-paclitaxel and PEGPH20.

Patients with a prior TE will be treated with therapeutic dose and schedule of rivaroxaban (15 mg BID for 21 days for induction if indicated, then 20 mg QD for chronic treatment), together with standard dose and schedule of gemcitabine, nab-paclitaxel and PEGPH20.

Nab-paclitaxel

PEGPH20

Kenneth Yu, MD, MSc

The purpose of this study is to test any good and bad effects of the study drug called PEGPH20. PEGPH20 alone is considered investigational. The Food and Drug Administration (FDA) has not approved the marketing or sale of PEGPH20, but have authorized its use in research studies with humans. PEGPH20 could shrink the cancer but it also can cause side effects. PEGPH20 is an enzyme that breaks down a specific tissue component called hyaluronan produced by some tumors. Pancreatic tumors often have a large amount of hyaluronan. The removal of hyaluronan from tumors may decrease tumor growth.

Study Of Gemcitabine, Nab-paclitaxel, PEGPH20 and Rivaroxaban for Advanced Pancreatic Adenocarcinoma

Pilot Study Of Gemcitabine, Nab-paclitaxel, PEGPH20 and Rivaroxaban for Advanced Pancreatic Adenocarcinoma

This includes any grade 2 or grade 3 thromboembolic event as defined by NCI CTCAE v4.0 found on incidental imaging, which would indicate a need for medical intervention.

Halozyme Therapeutics

Miami Cancer Institute

Memorial Sloan Kettering Cancer Center

Gastrointestinal Neoplasms

Digestive System Neoplasms

Endocrine Gland Neoplasms

Gastrointestinal Diseases

Pancreatic Diseases

Endocrine System Diseases

Pembrolizumab

Lenvatinib

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Patients receive pembrolizumab IV over 30 minutes on day 1 and lenvatinib mesylate PO QD on days 1-21. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Lenvatinib Mesylate

Vincent Chung

This phase II trial studies the effects of lenvatinib and pembrolizumab maintenance therapy in treating patients with pancreatic cancer that has spread to other places in the body (advanced) and cannot be removed by surgery (unresectable). Lenvatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving lenvatinib and pembrolizumab may be effective as a maintenance therapy in patients with pancreatic cancer.

PRIMARY OBJECTIVE:

I. To evaluate the progression free survival (PFS) of lenvatinib mesylate (lenvatinib)-pembrolizumab as maintenance therapy in patients with advanced unresectable pancreatic cancer who have achieved partial response or stable disease following 1st or 2nd line therapy.

SECONDARY OBJECTIVES:

I. To evaluate the safety and tolerability associated with the combination of lenvatinib-pembrolizumab as maintenance therapy for patients with advanced unresectable pancreatic cancer.

II. To evaluate the overall response rate (ORR), including confirmed and unconfirmed, complete and partial response and duration of response, of patients treated with lenvatinib-pembrolizumab in the subset of patients with measurable disease.

III. To evaluate if potential gains in PFS translates into an overall survival (OS) benefit for patients with pancreatic cancer being treated with lenvatinib-pembrolizumab in the maintenance setting.

EXPLORATORY OBJECTIVES:

I .To investigate whether lenvatinib-pembrolizumab induces measurable immune-related systemic changes in peripheral blood over the course of therapy by flow cytometry using T cell markers (e.g. CD4+, CD8+, PD1, TIM-3, LAG-3, TOX nuclear factor).

II. To conduct an exploratory study to identify global changes in expression of tumor-related genes using needle biopsy samples of PDA tumors obtained prior to and within one week after the 3rd cycle of pembrolizumab.

OUTLINE:

Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1 and lenvatinib mesylate orally (PO) once daily (QD) on days 1-21. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days and then up to 1 year.

Lenvatinib and Pembrolizumab Maintenance Therapy for the Treatment of Patients of Advanced Unresectable Pancreatic Cancer

Phase II Trial of Lenvatinib-Pembrolizumab Maintenance Therapy in Patients With Advanced Unresectable Pancreatic Cancer

Progression and response will be assessed using Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1 and immune-modified (i)RECIST.

Based on Common Terminology Criteria for Adverse Events 5.0.

National Cancer Institute (NCI)

City of Hope Medical Center

Patients receive FL118 PO on days 1, 8, and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of blood samples and CT or MRI throughout the trial. Patients may optionally undergo biopsy at screening and on study.

Biopsy

Biospecimen Collection

Computed Tomography

DDX5 Degrader FL118

Magnetic Resonance Imaging

Christos Fountzilas

This phase I trial tests the safety, side effects, and best dose of FL118 in treating patients with pancreatic ductal adenocarcinoma that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced). FL118 is a small anti-tumor molecule that inhibits the expression of multiple cancer-associated anti-apoptotic proteins. An anti-apoptotic protein is a protein that interferes with or inhibits cell death. In adults, apoptosis is used to rid the body of cells that have been damaged beyond repair. Apoptosis also plays a role in preventing cancer. If apoptosis is for some reason prevented, it can lead to uncontrolled cell production that can subsequently develop into a tumor. FL118 has been shown to inhibit or block the proteins that prevent damaged/mutated (genetically changed) cells from dying, and, by doing so, prevent the growth of cancerous cells and tumor development.

PRIMARY OBJECTIVES:

I. To establish the safety, schedule, and dosing of DDX5 degrader FL118 (FL118) in patients with advanced pancreatic ductal adenocarcinoma (PDAC).

II. To determine the pharmacokinetics (PK) of FL118 in patients with advanced PDAC.

SECONDARY OBJECTIVES:

I. To determine the pharmacodynamics (PD) of FL118 in patients with advanced PDAC.

II. To determine the preliminary antineoplastic efficacy of FL118 in patients with advanced PDAC.

EXPLORATORY OBJECTIVES:

I. To evaluate biomarkers predictive of response or resistance. II. Evaluate changes in the tumor microenvironment. III. To determine the significance of somatic and germline DNA damage repair mutations as predictive biomarkers of antineoplastic activity.

OUTLINE: This is a dose-escalation study of FL118 followed by a dose-expansion study.

Patients receive FL118 orally (PO) on days 1, 8, and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of blood samples and computed tomography (CT) or magnetic resonance imaging (MRI) throughout the trial. Patients may optionally undergo biopsy at screening and on study.

After completion of study treatment, patients are followed up at 30 days and then every 3 months for up to 12 months.

FL118 for Treating Patients With Advanced Pancreatic Ductal Adenocarcinoma

First-in-Human Phase I Trial of FL118 in Patients With Advanced Pancreatic Ductal Adenocarcinoma

Toxicity and adverse events will be assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0.

The MTD will be determined from the observed dose limiting toxicities per cohort using an accelerated dose-escalation design.

The recommended phase 2 dose will be determined based on the MTD (or highest dose administered if the MTD is not reached), the pharmacokinetic/pharmacodynamic modeling, and overall clinical safety and efficacy data.

PK parameters of maximum plasma concentration

apparent clearance of the analyte in the plasma

Will be assessed use a two-stage, single-arm Simon minimax design.

The disease control (complete response + partial response + stable disease) will be summarized using frequencies and relative frequencies. The disease control rate will be estimated with a 95% credible region obtained by Jeffrey's prior method.

Will be summarized using standard Kaplan-Meier methods, where estimates of median survival will be obtained with 95% confidence intervals.

Roswell Park Cancer Institute

Central Nervous System Depressants

Other Dietary Supplements

Benzocaine

Tannic Acid

KN046+Nab-Paclitaxel+Gemcitabine In combine therapy stage, KN046 is 5 milligram per kilogram, every 2 weeks. In maintain stage, KN046 is 5 milligram per kilogram, every 2 weeks.

KN046

placebo+Nab-Paclitaxel+Gemcitabine In combine therapy stage, placebo is 5 milligram per kilogram, every 2 weeks. In maintain stage, placebo is 5 milligram per kilogram, every 2 weeks.

placebo

This study is a multicenter, randomized, double-Blind Phase III Study to compare the clinical efficacy and safety of KN046 plus gemcitabine and nab-paclitaxel versus placebo plus gemcitabine and nab-paclitaxel in subjects with advanced pancreatic ductal adenocarcinoma who have not previously received systemic treatment.

KN046 in Subjects With Advanced Pancreatic Ductal Adenocarcinoma.

A Multicenter, Randomized, Double-Blind Phase III Study to Assess the Efficacy and Safety of KN046 Combined With Gemcitabine and Nab-Paclitaxel Versus Placebo Combined With Gemcitabine and Nab-Paclitaxel in First Line Advanced Pancreatic Ductal Adenocarcinoma Subjects (ENREACH-PDAC-01).

OS was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the interim analysis were censored at the date of the last follow-up.

Time between randomization to date of disease progression or death due to any cause.

Complete Response or Partial Response according to RECIST

Jiangsu Alphamab Biopharmaceuticals Co., Ltd

Camurati-Engelmann Disease

Antibodies

Immunomodulating Agents

Antibodies, Bispecific

Immunoglobulins

Immunologic Factors

Treatment is AGEN1423 plus balstilimab for 4 cycles (8 weeks) followed by balstilimab alone for up to 2 years. AGEN1423 will be administered in a total of 4 doses. Balstilimab will be administered every 2 weeks.

Treatment is AGEN1423 plus balstilimab in combination with gemcitabine and nab-paclitaxel for 2 cycles (8 weeks) followed by balstilimab in combination with gemcitabine and nab-paclitaxel for up to 2 years. AGEN1423 will be administered in a total of 4 doses. Balstilimab will be administered once every 2 weeks.

via IV, dosage per protocol, once every 2 weeks for up to 8 weeks

AGEN1423

via IV, dosage per protocol, once evert 2 weeks, up to 2 years

Balstilimab

Bruno Bockorny, MD

The goal of this research study is to asses the safety and efficacy of the combination of AGEN1423 and Balstilimab with or without chemotherapies, gemcitabine and nab-paclitaxel, for the treatment of advanced pancreatic ductal adenocarcinoma (PDAC) which has progressed after at least one previous line of cancer therapy.

The names of the study drugs involved in this study are:

* AGEN1423
* Balstilimab

Participants will receive study treatment for about 2 years and will be followed for 1 year after.

The research study procedures include screening for eligibility and study treatment including evaluations and follow up visits.

* Participants will receive study treatment for about 2 years and will be followed for 1 year. If the combination is considered to be safe and tolerable, and objective response is achieved in at least 2 patients, the study will proceed to Cohort 2.
* This research study involves immunotherapy. The names of the study drugs involved in this study are:
* AGEN1423
* Balstilimab

It is expected that about 24 people will take part in this part of this research

This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational drug to learn whether the drug works in treating a specific disease. "Investigational" means that the drug is being studied. The U.S. Food and Drug Administration (FDA) has not approved AGEN1423 as a treatment for any disease. The U.S. Food and Drug Administration (FDA) has not approved Balstilimab as a treatment for any disease.

Agenus, a pharmaceutical company, is supporting this research study by providing funding and study drug for the research study.

AGEN1423 Plus Balstilimab With or Without Chemo in Pancreatic Cancer

A Phase 2 Study of AGEN1423, an Anti-CD73-TGFβ-Trap Bifunctional Antibody, in Combination With Balstilimab, With or Without Chemotherapy in Subjects With Advanced Pancreatic Cancer.

The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: \[contact information for Sponsor Investigator or designee\]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.

The objective response rate (ORR) is defined as the proportion of participants achieving complete response (CR) or partial response (PR) based on RECISTv1.1 criteria, using the modified intent-to-treat (mITT) analysis set

Disease control rate (DCR) defined as the sum of stable disease, partial and complete responses according to RECISTv1.1 criteria.

Duration of Overall Response (DOR), estimated using the Kaplan Meier method, is measured from the time measurement criteria are met for CR or PR (whichever is first recorded) per RECISTv1.1, until the first date that recurrent or progressive disease is objectively documented. Patients without progressive disease are censored at the date of last disease assessment.

Overall Survival (OS) based on the Kaplan-Meier method is defined as the time from study entry to death or censored at date last known alive.

Progression-free survival based on the Kaplan-Meier method is defined as the duration between randomization and documented disease progression (PD) or death, or is censored at time of last dsease assessment.

All grade 3-5 adverse events (AE) with treatment attribution of possibly, probably or definite based on CTCAEv5 that are not resolved in accordance with treatment guidelines were counted. Rate is the proportion of treated participants experiencing at least one of these adverse events as defined during the time of observation.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Study Of Gemcitabine, Nab-paclitaxel, PEGPH20 and Rivaroxaban for Advanced Pancreatic Adenocarcinoma	NCT02921022	Pancreatic Canc... Advanced Pancre...	Gemcitabine Nab-paclitaxel PEGPH20	18 Years -	Memorial Sloan Kettering Cancer Center
Lenvatinib and Pembrolizumab Maintenance Therapy for the Treatment of Patients of Advanced Unresectable Pancreatic Cancer	NCT04887805	Advanced Pancre... Stage II Pancre... Stage IIA Pancr... Stage IIB Pancr... Stage III Pancr... Stage IV Pancre... Unresectable Pa...	Lenvatinib Mesy... Pembrolizumab	18 Years -	City of Hope Medical Center
Study Of Gemcitabine, Nab-paclitaxel, PEGPH20 and Rivaroxaban for Advanced Pancreatic Adenocarcinoma	NCT02921022	Pancreatic Canc... Advanced Pancre...	Gemcitabine Nab-paclitaxel PEGPH20	18 Years -	Memorial Sloan Kettering Cancer Center
FL118 for Treating Patients With Advanced Pancreatic Ductal Adenocarcinoma	NCT06206876	Advanced Pancre... Locally Advance... Metastatic Panc... Refractory Panc... Stage II Pancre... Stage III Pancr... Stage IV Pancre... Unresectable Pa...	Biopsy Biospecimen Col... Computed Tomogr... DDX5 Degrader F... Magnetic Resona...	18 Years -	Roswell Park Cancer Institute
Lenvatinib and Pembrolizumab Maintenance Therapy for the Treatment of Patients of Advanced Unresectable Pancreatic Cancer	NCT04887805	Advanced Pancre... Stage II Pancre... Stage IIA Pancr... Stage IIB Pancr... Stage III Pancr... Stage IV Pancre... Unresectable Pa...	Lenvatinib Mesy... Pembrolizumab	18 Years -	City of Hope Medical Center
KN046 in Subjects With Advanced Pancreatic Ductal Adenocarcinoma.	NCT05149326	Advanced Pancre...	KN046 placebo	18 Years - 85 Years	Jiangsu Alphamab Biopharmaceuticals Co., Ltd
AGEN1423 Plus Balstilimab With or Without Chemo in Pancreatic Cancer	NCT05632328	Advanced Pancre... Pancreatic Duct... Pancreatic Canc...	AGEN1423 Balstilimab Gemcitabine Nab-paclitaxel	18 Years -	Beth Israel Deaconess Medical Center
AGEN1423 Plus Balstilimab With or Without Chemo in Pancreatic Cancer	NCT05632328	Advanced Pancre... Pancreatic Duct... Pancreatic Canc...	AGEN1423 Balstilimab Gemcitabine Nab-paclitaxel	18 Years -	Beth Israel Deaconess Medical Center

Spots Global Cancer Trial Database for advanced pancreatic ductal adenocarcinoma