History of Changes for Study: NCT04471727

Study in Patients With Advanced Cancers Associated With Expression of DLL3 Who Have Failed Standard Available Therapy

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Study Record Versions

Version	Submitted Date	Changes
1	July 13, 2020	None (earliest Version on record)
2	November 23, 2020	Recruitment Status, Study Status, Contacts/Locations and Oversight
3	December 4, 2020	Study Status and Contacts/Locations
4	January 13, 2021	Contacts/Locations and Study Status
5	January 25, 2021	Contacts/Locations and Study Status
6	March 11, 2021	Contacts/Locations, Study Status, Study Design and Study Identification
7	May 19, 2021	Study Status and Contacts/Locations
8	June 17, 2021	Study Status and Contacts/Locations
9	July 15, 2021	Study Status and Contacts/Locations
10	August 18, 2021	Study Status and Contacts/Locations
11	August 27, 2021	Contacts/Locations and Study Status
12	November 12, 2021	Contacts/Locations and Study Status
13	January 11, 2022	Contacts/Locations and Study Status
14	March 22, 2023	Outcome Measures, Contacts/Locations, Arms and Interventions, Study Status, Study Identification, Eligibility, Study Design and Study Description
15	July 21, 2023	Contacts/Locations and Study Status
16	December 8, 2023	Study Status and Contacts/Locations

Comparison Format:

Merged
Side-by-Side

Study Identification


Unique Protocol ID:	HPN328-4001
Brief Title:	Study in Patients With Advanced Cancers Associated With Expression of DLL3 Who Have Failed Standard Available Therapy
Official Title:	A Phase 1/2 Open-label, Multicenter, Dose Escalation and Dose Expansion Study of the Safety, Tolerability, and Pharmacokinetics of HPN328 in Patients With Advanced Cancers Associated With Expression of Delta Like Canonical Notch Ligand 3 (DLL3) Who Have Failed Standard Available Therapy
Secondary IDs:

Study Status


Record Verification:	June 2020
Overall Status:	Not yet recruiting
Study Start:	November 2020
Primary Completion:	December 2022 [Anticipated]
Study Completion:	March 2023 [Anticipated]

First Submitted:	July 6, 2020
First Submitted that Met QC Criteria:	July 13, 2020
First Posted:	July 15, 2020 [Actual]

Last Update Submitted that Met QC Criteria:	July 13, 2020
Last Update Posted:	July 15, 2020 [Actual]

Sponsor/Collaborators


Sponsor:	Harpoon Therapeutics
Responsible Party:	Sponsor
Collaborators:

Oversight


U.S. FDA-regulated Drug:	Yes
U.S. FDA-regulated Device:	No
Data Monitoring:	No

Study Description


Brief Summary:	An open-label, Phase 1/2 study of HPN328 as monotherapy to assess the safety, tolerability and PK in patients with advanced cancers associated with expression of DLL3.
Detailed Description:

Conditions


Conditions:	Small-cell Lung Cancer
Keywords:	Lung Cancer Small-Cell Lung Cancer DLL3 Harpoon TriTAC Prostate Cancer Neuroendocrine Tumors High Grade Neuroendrocrine Features Delta Like Canonical Notch Ligand 3

Study Design


Study Type:	Interventional
Primary Purpose:	Treatment
Study Phase:	Phase 1/Phase 2
Interventional Study Model:	Sequential Assignment
Number of Arms:	2
Masking:	Single (Participant)
Allocation:	Non-Randomized
Enrollment:	52 [Anticipated]

Arms and Interventions

Arms	Assigned Interventions
Experimental: Part 1 (Dose Escalation) HPN328 is IV administered once weekly for about 1 hour. Doses will vary between cohorts as MTD is being determined.	Drug: HPN328 HPN328 is a tri-specific recombinant protein construct (Tri-specific T Cell Activating Construct [TriTAC®]) containing 3 humanized antibody derived binding domains
Experimental: Part 2 (Dose Expansion) HPN328 is IV administered once weekly for about 1 hour at the recommended phase 2 dose (2) established in Part 1.	Drug: HPN328 HPN328 is a tri-specific recombinant protein construct (Tri-specific T Cell Activating Construct [TriTAC®]) containing 3 humanized antibody derived binding domains

Outcome Measures


Primary Outcome Measures:
1.	Assessment of Adverse Events by CTCAE 5.0 of HPN 328 [ Time Frame: 3 years ] Assess safety and tolerability at increasing dose levels of HPN328 in successive cohorts of patients with solid tumors associated with DLL3 expression by adverse events (CTCAE v5.0)
2.	Determine MTD/RP2D [ Time Frame: 2 years ] Estimate the maximum tolerated dose (MTD) or select the recommended Phase 2 dose (RP2D)
3.	Characterize the pharmacokinetics (PK) of HPN328 [ Time Frame: 2 years ] Evaluate of levels of HPN328 in blood serum
Secondary Outcome Measures:
1.	Determine preliminary activity of HPN328 [ Time Frame: 3 years ] Evaluate preliminary efficacy of HPN328 based on disease assessment using RECISTv1.1
2.	Determine the immunogenicity [ Time Frame: 3 years ] Evaluate the immunogenicity of HPN328 assessing Anti-drug Antibodies in blood serum

Eligibility


Minimum Age:	18 Years
Maximum Age:	100 Years
Sex:	All
Gender Based:
Accepts Healthy Volunteers:	No
Criteria:	Major Inclusion Criteria: Histologically or cytologically confirmed malignancy associated with expression of DLL3: SCLC that has relapsed following at least 1 line of platinum-based chemotherapy Malignancy other than SCLC with pathologic demonstration of high-grade neuroendocrine features or demonstration of DLL3 expression in a tumor sample, and that the patient has 1 of the following: Disease that is relapsed/refractory to standard systemic therapy, Disease for which standard therapy does not exist, or Disease where standard therapy is not considered appropriate by the Investigator Available archival tissue sample or fresh biopsy tissue sample must be available for shipment prior to enrollment. Patients with no available tumor tissue, who cannot safely undergo a biopsy may be eligible if they have documentation of DLL3 expression in a tumor sample from a prior biopsy. Adequate hematologic status, including: Absolute neutrophil count (ANC) ≥1500 cells/μL Platelet count ≥100,000/μL Hemoglobin ≥9 g/dL (no transfusions allowed within 2 weeks prior to screening) Adequate renal function, including: -Calculated creatinine clearance ≥50 mL/min using the formula of Cockcroft and Gault Adequate liver function, including Total bilirubin ≤1.5 x upper limit of normal (ULN), regardless of direct bilirubin, unless the patient has documented Gilbert syndrome in which case the maximum total serum bilirubin should be 5 mg/dL Aspartate and alanine transaminase (AST and ALT) ≤3 x ULN Major Exclusion Criteria: Untreated brain metastases. Participants must have completed treatment for brain metastasis, and be neurologically stable off steroids, for at least 7 days prior to first dose of study drug Patients with glioma or other primary CNS malignancy Patients with spinal cord compression or symptomatic/uncontrolled epidural disease. Patients with previously treated spinal cord compression or epidural disease may be eligible if stable for at least 1 week prior to first dose of study drug. Active neurologic paraneoplastic syndrome. Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (e.g., biweekly or more frequently).

Contacts/Locations


Locations:

IPDSharing


Plan to Share IPD:

References


Citations:
Links:
Available IPD/Information: