Clinical trial NCT05814666: Activity and Safety of Danvatirsen and Pembrolizumab in HNSCC
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
Overall status: RECRUITING
Phase: PHASE2
Conditions: HNSCC
Lead sponsor: Flamingo Therapeutics NV
Sponsor class: INDUSTRY
First posted: 2023-04-18
Enrollment: 81
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

1. Must have given written informed consent (signed and dated).
2. Aged ≥18 years at the time of informed consent.
3. 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.
4. Presence of measurable tumor per RECIST v1.1 criteria.
5. Detectable PD-L1 expression in tumor, defined as CPS ≥1 determined by a FDA or national regulatory agency of the country in which the patient resides.-approved test.
6. Baseline fresh tumor biopsy or archival specimen.
7. ECOG performance status of 0 or 1.
8. Adequate organ function within 10 days of study treatment,
9. Oxygen saturation on room air ≥92% by pulse oximetry.
10. Females must be non-pregnant and non-lactating and either be postmenopausal or agree to adequate birth control.
11. Males must be surgically sterile or agree to adequate birth control.
12. Has an estimated life expectancy of at least 3 months.
13. Has recovered from all complications or surgery and all toxicities of prior therapy

Exclusion Criteria:

1. Prior therapy for metastatic HNSCC.
2. Has disease suitable for local therapy with curative intent.
3. Primary tumor of the nasopharynx.
4. Has received prior therapy with an anti-programmed death 1 (PD-1), anti PD L1, or anti-programmed death-ligand-2 (PD-L2).
5. Radiation therapy (or other non-systemic therapy) within 2 weeks of Day 1 of study treatment.
6. Known autoimmune disease that has required systemic treatment
7. Known immunodeficiency or receiving systemic steroid therapy that would be the equivalent of \>10 mg prednisone daily
8. Prior allogeneic tissue/solid organ transplant.
9. Has significant cardiovascular disease
10. Has received a live vaccine within 30 days
11. Active infection requiring systemic antiviral or antimicrobial therapy
12. History of (non-infectious) pneumonitis that required steroids or current pneumonitis.
13. History of other malignancies
14. Active HIV infection except patients who are currently stable on antiretroviral therapy for at least 4 weeks
15. Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection.
16. Treated or untreated parenchymal brain metastases or leptomeningeal disease.
17. 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.
18. Hypersensitivity to any component of danvatirsen or pembrolizumab.

Primary outcomes:
measure: Confirmed ORR
timeFrame: Up to 18 months
Secondary outcomes:
measure: Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
timeFrame: Up to 18 months
measure: DOR
timeFrame: Up to 18months
measure: DCR & CR Rate
timeFrame: Up to 18months
measure: ORR in tumors with CPS ≥50
timeFrame: Up to 18months
measure: DOR in tumors with CPS ≥50
timeFrame: Up to 18months
measure: PFS
timeFrame: Up to 18months
measure: OS
timeFrame: Up to 30months
measure: Maximum plasma concentration
timeFrame: Up to 18 months
measure: Trough concentration
timeFrame: Up to 18 months
measure: Area under the plasma concentration-time curve
timeFrame: Up to 18 months
measure: Time to maximum plasma concentration
timeFrame: Up to 18 months
measure: Immunogenicity of danvatirsen
timeFrame: Up to 18 months
Other outcomes:
Locations:
city: Tucson
country: United States
facility: The University of Arizona Cancer Center
state: Arizona
city: Irvine
country: United States
facility: University of California Irvine (UCI)
state: California
city: Torrance
country: United States
facility: TMPN Hunt Cancer Care
state: California
city: Westwood
country: United States
facility: University of California Los Angeles
state: California
city: Aurora
country: United States
facility: University of Colorado Hospital (UCH) Anschutz Cancer Pavilion
state: Colorado
city: Miami
country: United States
facility: Miami Cancer Institute
state: Florida
city: Atlanta
country: United States
facility: Emory University Hospital Midtown
state: Georgia
city: Chicago
country: United States
facility: University of Illinois Cancer Center
state: Illinois
city: Merriam
country: United States
facility: AMR Kansas City Oncology
state: Kansas
city: Westwood
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Baton Rouge
country: United States
facility: Mary Bird Perkins Cancer Center
state: Louisiana
city: Baltimore
country: United States
facility: University of Maryland Baltimore, Greenebaum Comprehensive Cancer Center
state: Maryland
city: Las Vegas
country: United States
facility: Comprehensive Cancer Centers of Nevada
state: Nevada
city: Morristown
country: United States
facility: Morristown Medical Center
state: New Jersey
city: New York
country: United States
facility: Mount Sinai
state: New York
city: Stony Brook
country: United States
facility: Stony Brook Cancer Center
state: New York
city: Cincinnati
country: United States
facility: The Christ Hospital Cancer Center
state: Ohio
city: Cincinnati
country: United States
facility: University of Cincinnati Medical Center
state: Ohio
city: Cleveland
country: United States
facility: University Hospitals Cleveland
state: Ohio
city: Greenville
country: United States
facility: Prisma Health Cancer Institute
state: South Carolina
city: Dallas
country: United States
facility: UT Southwestern Medical Center/Simmons Comprehensive Cancer Center
state: Texas
city: Busan
country: Korea, Republic of
facility: Dong-A University Hospital
city: Busan
country: Korea, Republic of
facility: Kosin University College of Medicine - Kosin University Gospel Hospital (KUGH)
city: Jinju
country: Korea, Republic of
facility: Gyeongsang National University Hospital
city: Seoul
country: Korea, Republic of
facility: Korea University Medical Center (KUMC)
city: Seoul
country: Korea, Republic of
facility: The Catholic University of Korea - Eunpyeong St. Mary's Hospital
city: Leeds
country: United Kingdom
facility: Saint James's University Hospital (SJUH) - St James's Institute of Oncology
city: Liverpool
country: United Kingdom
facility: The Clatterbridge Cancer Centre NHS Foundation Trust
city: London
country: United Kingdom
facility: Barts Health MHS Trust (Barts and The London NHS Trust) - St Bartholomew's (Barts) Hospital
city: London
country: United Kingdom
facility: The Royal Marsden NHS Foundation Trust
city: Northwood, Middlesex
country: United Kingdom
facility: East and North Hertfordshire NHS Trust, Lister Hospital
city: Surry
country: United Kingdom
facility: The Royal Marsden NHS Foundation Trust
Study officials:
References: