Clinical Trials Logo

Clinical Trial Summary

This study is the study of the combination of PEGPH20 and Pembrolizumab (MK-3475) for patients with previously treated Hyaluronan High (HA-high) metastatic pancreatic ductal adenocarcinoma. This study is an interventional, unblinded, open label study. Approximately 35 subjects will be enrolled. The trial will require approximately a total of 18 months, including 12 months for enrollment, with an additional 6 months for patient follow-up, data collection and study closure.

Each subject will participate in the trial from the time the subject signs the Informed Consent Form (ICF) through the final contact. After a screening phase of up to 21 days, eligible subjects will receive PEGPH20 beginning with Cycle 1 Day 1, on Days 1, 8 15 of every 3 week-cycles and pembrolizumab beginning on Cycle 1 Day 1 (2-4 hrs after PEGPH20), every 3-week-cycles.

Treatment with PEGPH20 and pembrolizumab will continue until progressive disease (PD), unacceptable adverse events (AEs), intercurrent illness that prevents further administration of treatment, investigator's decision to withdraw the subject, subject withdraws consent, pregnancy of the subject, noncompliance with trial treatment or procedure requirements, subject receives 35 treatments (approximately 24 months) of pembrolizumab, or administrative reasons requiring cessation of treatment. Subjects who discontinue for reasons other than PD will have post-treatment follow-up for disease status until PD, initiating a non-study cancer treatment, withdrawing consent, or becoming lost to follow-up. All subjects will be followed by telephone for overall survival (OS) until death, withdrawal of consent, or the end of the study.

After the end of treatment, each subject will be followed for 30 days for AE monitoring. Serious adverse events (SAE) and events of clinical interest (ECI) will be collected for 90 days after the end of treatment or for 30 days after the end of treatment if the subject initiates new anticancer therapy, whichever is earlier.


Clinical Trial Description

Combination strategies geared towards blocking the PD1/PD-L1 inhibitory pathway, such as with pembrolizumab, concurrent with stroma depletion (PEGPH20) may induce synergistic anti-cancer activity and immune responses in pancreatic cancer. Effective harnessing of the immune system and rational combinations with stroma-targeting biological agents (PEGPH20) is a novel field that needs to be explored in pancreatic cancer. This phase II trial will determine the efficacy of pembrolizumab plus PEGPH20 in metastatic pancreatic cancer patients who have HA-high tumor expression. Stroma and immune-related biomarkers will be tested prospectively in blood and tumor biopsies at baseline, after 6 weeks of therapy, and at time of cancer progression. A phase I study with pembrolizumab and PEGPH20 is ongoing in lung and gastric cancer patients (NCT02563548), and demonstrated safety and tolerability of this combination at the doses administered in this study (Halozyme data).

Immunotherapies have the potential to induce durable therapeutic responses although this typically occurs in a small fraction of patients. Biomarker-guided patient selection can, in principle, identify those patients most likely to benefit. The investigators hypothesize that stroma remodeling with PEGPH20 will potentiate effector CD8 T cell lymphocyte infiltration and sensitize pancreatic cancer to immune therapy, and that immunologic, and/or genomic biomarkers will identify patient subsets most likely to benefit. As examples, MSI-high status and high tumor mutational burden (hypermutation) have been linked to sensitivity to immune checkpoint inhibitors (Le et al. 2015, Le et al. 2016).

Assays may include but are not limited to: Immunohistochemical analysis, profiling of the immune transcriptome, circulating cytokine analyses, flow cytometric analyses of peripheral and intratumoral immune response.

This is an open label non-randomized Phase II trial for patients with previously treated metastatic ductal pancreatic adenocarcinoma with HA-high expression, to assess the progression-free survival rate (PFS) of patients treated with this combination therapy. Secondary endpoints will assess safety and tolerability, overall response rate (ORR), disease control rate (DCR= CR+PR+SD), duration of response and stable disease (DOR), and overall survival (OS).

There will be an estimated 35 patients enrolled into the study, using 5 centers in the U.S.

Overall response rates as well as individual categories of response (CR, PR, SD, and PD) will be determined using RECIST 1.1. Time-to-event endpoints, including PFS and OS will be assessed using the Kaplan-Meier method. Toxicity (adverse events) will be recorded using the NCI CTCAE, version 5.0 (published Nov 2017, Appendix B).

All patients will start treatment with PEGPH20 3 microgram/kg IV weekly x 3, and pembrolizumab 200 mg IV every 3 weeks, in 3-week cycles.

Patients may remain on treatment with PEGPH20 in combination with pembrolizumab as long as they are receiving clinical benefit, until disease progression per RECIST 1.1 criteria, or until untolerable toxicity develops, whichever comes first. If no disease progression, patients will be allowed to remain on study treatment for up to 24 months. If no disease progression, but with unacceptable toxicity from PEGPH20, patients will be allowed to continue on pembrolizumab alone for up to 24 months if deemed appropriate by the investigator. If pembrolizumab needs to be discontinued for toxicity, patients may continue treatment with PEGPH20 alone.

The estimated duration for accrual is anticipated to be 12 months. Patients will be followed up for a minimum of 6 months. The overall study duration is estimated at approximately 18 months. ;


Study Design


Related Conditions & MeSH terms


NCT number NCT03634332
Study type Interventional
Source Pancreatic Cancer Research Team
Contact Amy Stoll-Dastice, MS
Phone 206-816-4239
Email amys@crab.org
Status Recruiting
Phase Phase 2
Start date May 1, 2019
Completion date January 2021

See also
  Status Clinical Trial Phase
Completed NCT05305001 - Germline Mutations Associated With Hereditary Pancreatic Cancer in Unselected Patients With Pancreatic Cancer in Mexico
Completed NCT02526017 - Study of Cabiralizumab in Combination With Nivolumab in Patients With Selected Advanced Cancers Phase 1
Recruiting NCT05497531 - Pilot Comparing ctDNA IDV vs. SPV Sample in Pts Undergoing Biopsies for Hepatobiliary and Pancreatic Cancers N/A
Recruiting NCT06054984 - TCR-T Cells in the Treatment of Advanced Pancreatic Cancer Early Phase 1
Recruiting NCT04927780 - Perioperative or Adjuvant mFOLFIRINOX for Resectable Pancreatic Cancer Phase 3
Recruiting NCT05919537 - Study of an Anti-HER3 Antibody, HMBD-001, With or Without Chemotherapy in Patients With Solid Tumors Harboring an NRG1 Fusion or HER3 Mutation Phase 1
Terminated NCT03140670 - Maintenance Rucaparib in BRCA1, BRCA2 or PALB2 Mutated Pancreatic Cancer That Has Not Progressed on Platinum-based Therapy Phase 2
Terminated NCT00529113 - Study With Gemcitabine and RTA 402 for Patients With Unresectable Pancreatic Cancer Phase 1
Recruiting NCT05168527 - The First Line Treatment of Fruquintinib Combined With Albumin Paclitaxel and Gemcitabine in Pancreatic Cancer Patients Phase 2
Active, not recruiting NCT04383210 - Study of Seribantumab in Adult Patients With NRG1 Gene Fusion Positive Advanced Solid Tumors Phase 2
Recruiting NCT05391126 - GENOCARE: A Prospective, Randomized Clinical Trial of Genotype-Guided Dosing Versus Usual Care N/A
Terminated NCT03300921 - A Phase Ib Pharmacodynamic Study of Neoadjuvant Paricalcitol in Resectable Pancreatic Cancer A Phase Ib Pharmacodynamic Study of Neoadjuvant Paricalcitol in Resectable Pancreatic Cancer Phase 1
Completed NCT03153410 - Pilot Study With CY, Pembrolizumab, GVAX, and IMC-CS4 (LY3022855) in Patients With Borderline Resectable Adenocarcinoma of the Pancreas Early Phase 1
Recruiting NCT03175224 - APL-101 Study of Subjects With NSCLC With c-Met EXON 14 Skip Mutations and c-Met Dysregulation Advanced Solid Tumors Phase 2
Recruiting NCT05679583 - Preoperative Stereotactic Body Radiation Therapy in Patients With Resectable Pancreatic Cancer Phase 2
Recruiting NCT04183478 - The Efficacy and Safety of K-001 in the Treatment of Advanced Pancreatic Cancer Phase 2/Phase 3
Terminated NCT03600623 - Folfirinox or Gemcitabine-Nab Paclitaxel Followed by Stereotactic Body Radiotherapy for Locally Advanced Pancreatic Cancer Early Phase 1
Recruiting NCT04584008 - Targeted Agent Evaluation in Digestive Cancers in China Based on Molecular Characteristics N/A
Recruiting NCT05351983 - Patient-derived Organoids Drug Screen in Pancreatic Cancer N/A
Completed NCT04290364 - Early Palliative Care in Pancreatic Cancer - a Quasi-experimental Study