Advanced Cancers Associated With Mesothelin ExpressionPhase 1NCT03872206
Study of HPN536 in Patients With Advanced Cancers Associated With Mesothelin Expression
A Phase 1 study testing HPN536 Fixed IV 6 to 560 ng/kg, HPN536 1 Prime Step IV 600-1200 ng/kg Target and 2 Prime Step IV 900-14000 ng/kg Target in people with Advanced Cancers Associated With Mesothelin Expression, run by Harpoon Therapeutics, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA) at 16 sites in United States.
Trial summary
An open-label, Phase 1/2a study of HPN536 as monotherapy to assess the safety, tolerability and PK in patients with advanced cancers associated with mesothelin expression.(Phase 2 portion of the study was not conducted.) Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Cancers Associated With Mesothelin Expression
- What is being tested?
- HPN536 Fixed IV 6 to 560 ng/kg, HPN536 1 Prime Step IV 600-1200 ng/kg Target and 2 Prime Step IV 900-14000 ng/kg Target
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 95 participants
- Where
- 16 sitesUnited States
- Study dates
- 16 Apr 2019to 4 Jan 2023
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
None listed.
Who cannot join
- Brain metastases unless previously treated. Patients with previously treated brain metastases may participate provided they are clinically stable for at least 4 weeks prior to study entry, and have no evidence of new or enlarging brain metastases
- Evidence of retroperitoneal fibrosis, mesothelial surface (pleura, pericardium, peritoneum) thickening of ≥4 mm; significant or increasing pleural/pericardial effusions, ascites or pericarditis at baseline deemed unrelated to the underlying malignancy based on computed tomography (CT), magnetic resonance imaging (MRI), or echocardiogram (ECHO); or prior history of pleurodesis, retroperitoneal fibrosis or mediastinal fibrosis.
- Previous Grade 3/4 infusion or hypersensitivity reaction (not immunotoxicity) to treatment with another monoclonal antibody.
- For patients with tumor types other than pleural mesothelioma: Ascites requiring >1 paracentesis for therapeutic purposes (i.e., not for diagnosis) within 1 month prior to Cycle 1 Day 1.
Trial locations and contacts
16 sites in 1 country.
16 sites in 1 country
United States16 sites
Massachusetts General Hospital
Boston, Massachusetts, 02114
University of Virginia Cancer Center
Charlottesville, Virginia, 22903
University of Chicago
Chicago, Illinois, 60637
Cleveland Clinic Taussig Cancer Institute
Cleveland, Ohio, 44195
Mary Crowley Cancer Research
Dallas, Texas, 75230
Mayo Clinic Florida
Jacksonville, Florida, 32224
University of Southern California
Los Angeles, California, 90007
University of California Los Angeles
Los Angeles, California, 90095-7170
Sarah Cannon Research Institute
Nashville, Tennessee, 37203
Memorial Sloan Kettering Cancer Center
New York, New York, 10017
Stephenson Cancer Center
Oklahoma City, Oklahoma, 73104
Thomas Jefferson University
Philadelphia, Pennsylvania, 19107
Mayo Clinic Arizona
Phoenix, Arizona, 85054
Mayo Clinic Rochester
Rochester, Minnesota, 55905
University of Washington Medical Center
Seattle, Washington, 98195
Washington University School of Medicine in St. Louis
St Louis, Missouri, 63110
About this study
Official title: A Phase 1/2a Open-label, Multicenter, Dose Escalation and Dose Expansion Study of the Safety, Tolerability, and Pharmacokinetics of HPN536 in Patients With Advanced Cancers Associated With Mesothelin Expression Who Have Failed Standard Available Therapy
An open-label, Phase 1/2a study of HPN536 as monotherapy to assess the safety, tolerability and PK in patients with advanced cancers associated with mesothelin expression.(Phase 2 portion of the study was not conducted.)
- Being tested
- HPN536 Fixed IV 6 to 560 ng/kg, HPN536 1 Prime Step IV 600-1200 ng/kg Target, 2 Prime Step IV 900-14000 ng/kg Target
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HPN536 Fixed IV 6 to 560 ng/kgBiological
Fixed dose IV cohorts at doses from 6 to 560 ng/kg
HPN536 1 Prime Step IV 600-1200 ng/kg TargetBiological
Step-dosing IV cohorts who received a single Prime Dose followed by the Target Dose (200/600 ng/kg, 200/1200 ng/kg, and 500/900 ng/kg)
2 Prime Step IV 900-14000 ng/kg TargetBiological
Step-dosing IV cohorts who received 2 Prime Doses followed by the Target Dose (200/600/900 ng/kg and 200/600/1200 ng/kg; 500/900/1200 ng/kg, 500/900/1800 ng/kg, 500/900/3600 ng/kg, 500/900/7200 ng/kg, and 500/900/14400 ng/kg)
| Study group | Role | What they receive |
|---|---|---|
| Fixed IV | Experimental | HPN536 administered once weekly via IV infusion in doses ranging from 6 to 560 ng/kg Receives: Biological: HPN536 Fixed IV 6 to 560 ng/kg |
| 1 Prime Step IV 600-1200 ng/kg Target | Experimental | Step-dosing IV cohorts who received a single Prime Dose followed by the Target Dose (200/600 ng/kg, 200/1200 ng/kg, and 500/900 ng/kg) Receives: Biological: HPN536 1 Prime Step IV 600-1200 ng/kg Target |
| 2 Prime Step IV 900-14000 ng/kg Target | Experimental | Step-dosing IV cohorts who received 2 Prime Doses followed by the Target Dose (200/600/900 ng/kg and 200/600/1200 ng/kg; 500/900/1200 ng/kg, 500/900/1800 ng/kg, 500/900/3600 ng/kg, 500/900/7200 ng/kg, and 500/900/14400 ng/kg) Receives: Biological: 2 Prime Step IV 900-14000 ng/kg Target |
What is being measured
The primary outcome is the main question the study is designed to answer.
Assessment of Adverse Events by CTCAE 5.0 of HPN536
Assess safety and tolerability at increasing dose levels of HPN536 in successive cohorts of patients with of patients with epithelial ovarian cancer, fallopian tube cancer, primary peritoneal cancer, pancreatic adenocarcinoma, or mesothelioma (pleural and primary peritoneal) by adverse events (CTCAE v5.0)
Measured: 3 years
Determine MTD/RP2D
Estimate the maximum tolerated dose (MTD) or select the recommended Phase 2 dose (RP2D)
Measured: 2 years
Efficacy of HPN536 at the recommended Phase 2 dose: overall response rate (ORR)
Evaluate overall response rate (ORR) as assessed by RECIST
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Mar 2019
- Study start16 Apr 2019
- Primary completion4 Jan 2023
- Study completion4 Jan 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Advanced Cancers Associated With Mesothelin ExpressionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 95 participants (actual)
Sponsor and investigators
- Lead sponsor
- Harpoon Therapeutics, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03872206
- Sponsor's protocol ID
- HPN536-2001
- Status last verified
- Jun 2024
- First submitted
- 11 Mar 2019
- Last updated
- 7 Jun 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Molloy ME, Austin RJ, Lemon BD, Aaron WH, Ganti V, Jones A, Jones SD, Strobel KL, Patnaik P, Sexton K, Tatalick L, Yu TZ, Baeuerle PA, Law CL, Wesche H. Preclinical Characterization of HPN536, a Trispecific, T-Cell-Activating Protein Construct for the Treatment of Mesothelin-Expressing Solid Tumors. Clin Cancer Res. 2021 Mar 1;27(5):1452-1462. doi: 10.1158/1078-0432.CCR-20-3392. Epub 2020 Dec 1.
PubMed 33262134
Study at a glance
From the registry record, last updated by the sponsor on 7 Jun 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1/2a Open-label, Multicenter, Dose Escalation and Dose Expansion Study of the Safety, Tolerability, and Pharmacokinetics of HPN536 in Patients With Advanced Cancers Associated With Mesothelin Expression Who Have Failed Standard Available Therapy
- ClinicalTrials.gov ID
- NCT03872206
- Acronym / sponsor ID
- HPN536-2001
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 95 participants (actual)
- Lead sponsor
- Harpoon Therapeutics, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)Industry (pharma, biotech, devices)
- Study start
- 16 Apr 2019 (actual)
- Primary completion
- 4 Jan 2023 (actual)
- Study completion
- 4 Jan 2023 (actual)
- First posted
- 13 Mar 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
An open-label, Phase 1/2a study of HPN536 as monotherapy to assess the safety, tolerability and PK in patients with advanced cancers associated with mesothelin expression.(Phase 2 portion of the study was not conducted.)
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Fixed IV | Experimental | Biological: HPN536 Fixed IV 6 to 560 ng/kgHPN536 administered once weekly via IV infusion in doses ranging from 6 to 560 ng/kg |
| 1 Prime Step IV 600-1200 ng/kg Target | Experimental | Biological: HPN536 1 Prime Step IV 600-1200 ng/kg TargetStep-dosing IV cohorts who received a single Prime Dose followed by the Target Dose (200/600 ng/kg, 200/1200 ng/kg, and 500/900 ng/kg) |
| 2 Prime Step IV 900-14000 ng/kg Target | Experimental | Biological: 2 Prime Step IV 900-14000 ng/kg TargetStep-dosing IV cohorts who received 2 Prime Doses followed by the Target Dose (200/600/900 ng/kg and 200/600/1200 ng/kg; 500/900/1200 ng/kg, 500/900/1800 ng/kg, 500/900/3600 ng/kg, 500/900/7200 ng/kg, and 500/900/14400 ng/kg) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (0 listed)
Key exclusion criteria (4 listed)
- Brain metastases unless previously treated. Patients with previously treated brain metastases may participate provided they are clinically stable for at least 4 weeks prior to study entry, and have no evidence of new or enlarging brain metastases
- Evidence of retroperitoneal fibrosis, mesothelial surface (pleura, pericardium, peritoneum) thickening of ≥4 mm; significant or increasing pleural/pericardial effusions, ascites or pericarditis at baseline deemed unrelated to the underlying malignancy based on computed tomography (CT), magnetic resonance imaging (MRI), or echocardiogram (ECHO); or prior history of pleurodesis, retroperitoneal fibrosis or mediastinal fibrosis.
- Previous Grade 3/4 infusion or hypersensitivity reaction (not immunotoxicity) to treatment with another monoclonal antibody.
- For patients with tumor types other than pleural mesothelioma: Ascites requiring >1 paracentesis for therapeutic purposes (i.e., not for diagnosis) within 1 month prior to Cycle 1 Day 1.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| HPN536 Fixed IV 6 to 560 ng/kgFixed dose IV cohorts at doses from 6 to 560 ng/kg | Biological | Fixed IV |
| HPN536 1 Prime Step IV 600-1200 ng/kg TargetStep-dosing IV cohorts who received a single Prime Dose followed by the Target Dose (200/600 ng/kg, 200/1200 ng/kg, and 500/900 ng/kg) | Biological | 1 Prime Step IV 600-1200 ng/kg Target |
| 2 Prime Step IV 900-14000 ng/kg TargetStep-dosing IV cohorts who received 2 Prime Doses followed by the Target Dose (200/600/900 ng/kg and 200/600/1200 ng/kg; 500/900/1200 ng/kg, 500/900/1800 ng/kg, 500/900/3600 ng/kg, 500/900/7200 ng/kg, and 500/900/14400 ng/kg) | Biological | 2 Prime Step IV 900-14000 ng/kg Target |
Primary outcome
Assessment of Adverse Events by CTCAE 5.0 of HPN536
Time frame: 3 years
Assess safety and tolerability at increasing dose levels of HPN536 in successive cohorts of patients with of patients with epithelial ovarian cancer, fallopian tube cancer, primary peritoneal cancer, pancreatic adenocarcinoma, or mesothelioma (pleural and primary peritoneal) by adverse events (CTCAE v5.0)
Determine MTD/RP2D
Time frame: 2 years
Estimate the maximum tolerated dose (MTD) or select the recommended Phase 2 dose (RP2D)
Efficacy of HPN536 at the recommended Phase 2 dose: overall response rate (ORR)
Time frame: 1 year
Evaluate overall response rate (ORR) as assessed by RECIST
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Jun 2024.
- Derived from this study: PubMed 33262134Molloy ME, Austin RJ, Lemon BD, Aaron WH, Ganti V, Jones A, Jones SD, Strobel KL, Patnaik P, Sexton K, Tatalick L, Yu TZ, Baeuerle PA, Law CL, Wesche H. Preclinical Characterization of HPN536, a Trispecific, T-Cell-Activating Protein Construct for the Treatment of Mesothelin-Expressing Solid Tumors. Clin Cancer Res. 2021 Mar 1;27(5):1452-1462. doi: 10.1158/1078-0432.CCR-20-3392. Epub 2020 Dec 1.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
16 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing HPN536 Fixed IV 6 to 560 ng/kg, HPN536 1 Prime Step IV 600-1200 ng/kg Target and 2 Prime Step IV 900-14000 ng/kg Target in people with Advanced Cancers Associated With Mesothelin Expression, run by Harpoon Therapeutics, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA) at 16 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 0 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 Jun 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 16 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Assessment of Adverse Events by CTCAE 5.0 of HPN536 (time frame: 3 years). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03872206, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Jun 2024.