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Activity and Safety of Danvatirsen and Pembrolizumab in HNSCC (PEMDA-HN)

Primary Purpose

HNSCC

Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Danvatirsen
Pembrolizumab
Sponsored by
Flamingo Therapeutics NV
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for HNSCC

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Must have given written informed consent (signed and dated). Aged ≥18 years at the time of informed consent. Recurrent/metastatic histologically or cytologically proven squamous cell carcinoma of the head and neck that is considered incurable by local therapy. Eligible primary tumor locations are oropharynx, oral cavity, hypopharynx, and larynx. Presence of measurable tumor per RECIST v1.1 criteria. Detectable PD-L1 expression in tumor, defined as CPS ≥20 determined by a Food and Drug Administration-approved test. Baseline fresh tumor biopsy or archival specimen. ECOG performance status of 0 or 1. Adequate organ function within 10 days of study treatment, Oxygen saturation on room air ≥92% by pulse oximetry. Females must be non-pregnant and non-lactating and either be postmenopausal or agree to adequate birth control. Males must be surgically sterile or agree to adequate birth control. Has an estimated life expectancy of at least 3 months. Has recovered from all complications or surgery and all toxicities of prior therapy Exclusion Criteria: Prior therapy for metastatic HNSCC. Has disease suitable for local therapy with curative intent. Primary tumor of the nasopharynx. Has received prior therapy with an anti-programmed death 1 (PD-1), anti PD L1, or anti-programmed death-ligand-2 (PD-L2). Radiation therapy (or other non-systemic therapy) within 2 weeks of Day 1 of study treatment. Known autoimmune disease that has required systemic treatment Known immunodeficiency or receiving systemic steroid therapy that would be the equivalent of >10 mg prednisone daily Prior allogeneic tissue/solid organ transplant. Has significant cardiovascular disease Has received a live vaccine within 30 days Active infection requiring systemic antiviral or antimicrobial therapy History of (non-infectious) pneumonitis that required steroids or current pneumonitis. History of other malignancies Active HIV infection except patients who are currently stable on antiretroviral therapy for at least 4 weeks Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. Treated or untreated parenchymal brain metastases or leptomeningeal disease. Treatment with another investigational drug, biological agent, or device within 1 month of screening, or 5 half-lives of investigational agent (if known), whichever is longer.

Sites / Locations

  • AMR Kansas City OncologyRecruiting
  • Comprehensive Cancer Centers of NevadaRecruiting
  • Prisma Health Cancer InstituteRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Danvatirsen plus pembrolizumab

Pembrolizumab

Arm Description

Danvatirsen dosing: Week 1: Danvatirsen intravenously (IV) on Days 1, 3, and 5 Week 2 and subsequent weeks: Danvatirsen IV weekly Pembrolizumab dosing: Pembrolizumab every 3 weeks after the Danvatirsen dose.

Pembrolizumab IV every 3 weeks after the Danvatirsen dose.

Outcomes

Primary Outcome Measures

Confirmed ORR
Determine the ORR (Partial response [PR] + CR defined according to RECIST v1.1) as determined by the Investigator for the combination of danvatirsen and pembrolizumab compared with pembrolizumab alone

Secondary Outcome Measures

Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
Drug induced toxicities are assessed and graded according to Common Toxicity Criteria for Adverse Events (CTCAE) Version 5.0.
DOR
Duration of Response by RECIST v1.1
DCR & CR Rate
Disease control rate and complete response rate by RECIST v1.1
ORR in tumors with CPS ≥50
Overall response rate per RECIST v1.1 in tumors with CPS ≥50
DOR in tumors with CPS ≥50
Duration of response by RECIST v1.1 in tumors with CPS ≥50
PFS
Progression-free survival by RECIST v1.1, defined as the time from randomization to the first documentation of progressive disease (PD) or death from any cause, whichever comes first
OS
Overall survival, defined as time from randomization to death from any cause
Maximum plasma concentration
Maximum concentration recorded [Cmax]of danvatirsen at defined timepoints in the combination regimen
Trough concentration
Trough concentration [Ctrough] of danvatirsen at defined timepoints in the combination regimen
Area under the plasma concentration-time curve
Area under the plasma concentration-time curve over the dosing interval [AUCtau] of danvatirsen at defined timepoints in the combination regimen
Time to maximum plasma concentration
Time to maximum plasma concentration [Tmax]) after single and multiple doses at defined timepoints in the combination regimen
Immunogenicity of danvatirsen
Anti-danvatirsen antibody titers at defined timepoints in the combination regimen

Full Information

First Posted
March 10, 2023
Last Updated
August 18, 2023
Sponsor
Flamingo Therapeutics NV
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1. Study Identification

Unique Protocol Identification Number
NCT05814666
Brief Title
Activity and Safety of Danvatirsen and Pembrolizumab in HNSCC
Acronym
PEMDA-HN
Official Title
An Open-Label, Phase II, Randomized, Controlled Study of Danvatirsen Plus Pembrolizumab Compared to Pembrolizumab Alone in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma (HNSCC)
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
September 30, 2023 (Anticipated)
Primary Completion Date
September 30, 2024 (Anticipated)
Study Completion Date
August 30, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Flamingo Therapeutics NV

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Open-label, Phase II, randomized, controlled study evaluating the efficacy and safety of danvatirsen in combination with pembrolizumab compared with pembrolizumab alone as first-line treatment of patients with recurrent/metastatic (R/M) HNSCC. Two-thirds of patients will be randomized to receive danvatirsen and pembrolizumab and one-third will be randomized to receive pembrolizumab alone.
Detailed Description
This is a multicenter, open-label, Phase II, randomized, controlled study to determine the efficacy, safety, and other indicators of clinical and biological activity of the combination of danvatirsen and pembrolizumab as first-line treatment for R/M HNSCC. After providing informed consent, patients will be assessed for eligibility during the screening phase of the study. All patients must be willing and able to provide a formalin fixed paraffin-embedded (FFPE) archival or fresh tumor sample collected during the screening period; a fresh biopsy is preferred if safe and feasible to obtain and consented to by the patient. Following the screening period, eligible patients will be randomized in a 2:1 ratio to danvatirsen + pembrolizumab or pembrolizumab monotherapy, respectively. Patients will receive treatment in 21-day cycles. Patients assigned to the pembrolizumab monotherapy arm will receive treatment until a criterion for discontinuation is met or a maximum of 24 months of treatment. Patients assigned to combination therapy will receive both treatments until a criterion for discontinuation is met or the patient has received a maximum of 24 months of treatment, after which they may remain on danvatirsen monotherapy. Patients in both treatment arms will have radiologic tumor assessments every 6 weeks (±1 week), regardless of treatment delays, until objective disease progression, initiation of new anticancer treatment, death, withdrawal of consent, or end of study, whichever occurs first. All patients who discontinue study treatment for any reason will have a safety follow-up visit 30 days (+7 days) after the last dose of study treatment and a follow-up for AEs 90 days (+7 days) after the last dose of pembrolizumab. Patients will be followed for survival at 12 week (±7 days) intervals until death or withdrawal of consent, whichever occurs first. Survival follow-up will continue until at least 15 months after the last patient is randomized in the study.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HNSCC

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
81 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Danvatirsen plus pembrolizumab
Arm Type
Experimental
Arm Description
Danvatirsen dosing: Week 1: Danvatirsen intravenously (IV) on Days 1, 3, and 5 Week 2 and subsequent weeks: Danvatirsen IV weekly Pembrolizumab dosing: Pembrolizumab every 3 weeks after the Danvatirsen dose.
Arm Title
Pembrolizumab
Arm Type
Active Comparator
Arm Description
Pembrolizumab IV every 3 weeks after the Danvatirsen dose.
Intervention Type
Drug
Intervention Name(s)
Danvatirsen
Other Intervention Name(s)
ISIS 481464, AZD9150
Intervention Description
Danvatirsen is a STAT3 targeting drug.
Intervention Type
Drug
Intervention Name(s)
Pembrolizumab
Other Intervention Name(s)
Keytruda
Intervention Description
Pembrolizumab is a monoclonal antibody that binds to the PD-1 receptor and blocks its interaction with PD-L1 and PD-L2
Primary Outcome Measure Information:
Title
Confirmed ORR
Description
Determine the ORR (Partial response [PR] + CR defined according to RECIST v1.1) as determined by the Investigator for the combination of danvatirsen and pembrolizumab compared with pembrolizumab alone
Time Frame
Up to 18 months
Secondary Outcome Measure Information:
Title
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
Description
Drug induced toxicities are assessed and graded according to Common Toxicity Criteria for Adverse Events (CTCAE) Version 5.0.
Time Frame
Up to 18 months
Title
DOR
Description
Duration of Response by RECIST v1.1
Time Frame
Up to 18months
Title
DCR & CR Rate
Description
Disease control rate and complete response rate by RECIST v1.1
Time Frame
Up to 18months
Title
ORR in tumors with CPS ≥50
Description
Overall response rate per RECIST v1.1 in tumors with CPS ≥50
Time Frame
Up to 18months
Title
DOR in tumors with CPS ≥50
Description
Duration of response by RECIST v1.1 in tumors with CPS ≥50
Time Frame
Up to 18months
Title
PFS
Description
Progression-free survival by RECIST v1.1, defined as the time from randomization to the first documentation of progressive disease (PD) or death from any cause, whichever comes first
Time Frame
Up to 18months
Title
OS
Description
Overall survival, defined as time from randomization to death from any cause
Time Frame
Up to 30months
Title
Maximum plasma concentration
Description
Maximum concentration recorded [Cmax]of danvatirsen at defined timepoints in the combination regimen
Time Frame
Up to 18 months
Title
Trough concentration
Description
Trough concentration [Ctrough] of danvatirsen at defined timepoints in the combination regimen
Time Frame
Up to 18 months
Title
Area under the plasma concentration-time curve
Description
Area under the plasma concentration-time curve over the dosing interval [AUCtau] of danvatirsen at defined timepoints in the combination regimen
Time Frame
Up to 18 months
Title
Time to maximum plasma concentration
Description
Time to maximum plasma concentration [Tmax]) after single and multiple doses at defined timepoints in the combination regimen
Time Frame
Up to 18 months
Title
Immunogenicity of danvatirsen
Description
Anti-danvatirsen antibody titers at defined timepoints in the combination regimen
Time Frame
Up to 18 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Must have given written informed consent (signed and dated). Aged ≥18 years at the time of informed consent. Recurrent/metastatic histologically or cytologically proven squamous cell carcinoma of the head and neck that is considered incurable by local therapy. Eligible primary tumor locations are oropharynx, oral cavity, hypopharynx, and larynx. Presence of measurable tumor per RECIST v1.1 criteria. Detectable PD-L1 expression in tumor, defined as CPS ≥20 determined by a Food and Drug Administration-approved test. Baseline fresh tumor biopsy or archival specimen. ECOG performance status of 0 or 1. Adequate organ function within 10 days of study treatment, Oxygen saturation on room air ≥92% by pulse oximetry. Females must be non-pregnant and non-lactating and either be postmenopausal or agree to adequate birth control. Males must be surgically sterile or agree to adequate birth control. Has an estimated life expectancy of at least 3 months. Has recovered from all complications or surgery and all toxicities of prior therapy Exclusion Criteria: Prior therapy for metastatic HNSCC. Has disease suitable for local therapy with curative intent. Primary tumor of the nasopharynx. Has received prior therapy with an anti-programmed death 1 (PD-1), anti PD L1, or anti-programmed death-ligand-2 (PD-L2). Radiation therapy (or other non-systemic therapy) within 2 weeks of Day 1 of study treatment. Known autoimmune disease that has required systemic treatment Known immunodeficiency or receiving systemic steroid therapy that would be the equivalent of >10 mg prednisone daily Prior allogeneic tissue/solid organ transplant. Has significant cardiovascular disease Has received a live vaccine within 30 days Active infection requiring systemic antiviral or antimicrobial therapy History of (non-infectious) pneumonitis that required steroids or current pneumonitis. History of other malignancies Active HIV infection except patients who are currently stable on antiretroviral therapy for at least 4 weeks Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. Treated or untreated parenchymal brain metastases or leptomeningeal disease. Treatment with another investigational drug, biological agent, or device within 1 month of screening, or 5 half-lives of investigational agent (if known), whichever is longer.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Flamingo Therapeutics
Phone
+1 484 482 0007
Email
clinical@flamingotx.com
Facility Information:
Facility Name
AMR Kansas City Oncology
City
Merriam
State/Province
Kansas
ZIP/Postal Code
66204
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Site Manager
Phone
913-386-7557
Facility Name
Comprehensive Cancer Centers of Nevada
City
Las Vegas
State/Province
Nevada
ZIP/Postal Code
89169
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Site Manager
Phone
702-862-1100
Facility Name
Prisma Health Cancer Institute
City
Greenville
State/Province
South Carolina
ZIP/Postal Code
29605
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Site Manager
Phone
864-522-2066

12. IPD Sharing Statement

Learn more about this trial

Activity and Safety of Danvatirsen and Pembrolizumab in HNSCC

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