Activity and Safety of Danvatirsen and Pembrolizumab in HNSCC

HNSCC Clinical Trial

— 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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05814666
• Other study ID #: FLM-6774-201
• Status: Recruiting
• Phase: Phase 2
• Start date: May 30, 2023
• Est. completion date: May 30, 2026

Study information

• Verified date: May 2024
• Source: Flamingo Therapeutics NV
• Contact: Flamingo Therapeutics
• Phone: +1 484 482 0007
• Email: clinical[@]flamingotx.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 81
• Est. completion date: May 30, 2026
• Est. primary completion date: May 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• HNSCC
• Squamous Cell Carcinoma of Head and Neck

Intervention

Drug:
• Danvatirsen
Danvatirsen is a STAT3 targeting drug.
• Pembrolizumab
Pembrolizumab is a monoclonal antibody that binds to the PD-1 receptor and blocks its interaction with PD-L1 and PD-L2

Locations

Country	Name	City	State
Korea, Republic of	Gyeongsang National University Hospital	Jinju
Korea, Republic of	Korea University Medical Center (KUMC)	Seoul
United States	University of Colorado Hospital (UCH) Anschutz Cancer Pavilion	Aurora	Colorado
United States	The Christ Hospital Cancer Center	Cincinnati	Ohio
United States	University of Cincinnati Medical Center	Cincinnati	Ohio
United States	University Hospitals Cleveland	Cleveland	Ohio
United States	Prisma Health Cancer Institute	Greenville	South Carolina
United States	University of California Irvine (UCI)	Irvine	California
United States	Comprehensive Cancer Centers of Nevada	Las Vegas	Nevada
United States	AMR Kansas City Oncology	Merriam	Kansas
United States	Miami Cancer Institute	Miami	Florida
United States	Mount Sinai	New York	New York
United States	Stony Brook Cancer Center	Stony Brook	New York
United States	TMPN Hunt Cancer Care	Torrance	California
United States	The University of Arizona Cancer Center	Tucson	Arizona
United States	University of California Los Angeles	Westwood	California
United States	University of Kansas Medical Center	Westwood	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
Flamingo Therapeutics NV

Countries where clinical trial is conducted

United States,  Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Up to 18 months
Secondary	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.	Up to 18 months
Secondary	DOR	Duration of Response by RECIST v1.1	Up to 18months
Secondary	DCR & CR Rate	Disease control rate and complete response rate by RECIST v1.1	Up to 18months
Secondary	ORR in tumors with CPS =50	Overall response rate per RECIST v1.1 in tumors with CPS = 20 and = 50	Up to 18months
Secondary	DOR in tumors with CPS =50	Duration of response by RECIST v1.1 in tumors with CPS =50	Up to 18months
Secondary	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	Up to 18months
Secondary	OS	Overall survival, defined as time from randomization to death from any cause	Up to 30months
Secondary	Maximum plasma concentration	Maximum concentration recorded [Cmax]of danvatirsen at defined timepoints in the combination regimen	Up to 18 months
Secondary	Trough concentration	Trough concentration [Ctrough] of danvatirsen at defined timepoints in the combination regimen	Up to 18 months
Secondary	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	Up to 18 months
Secondary	Time to maximum plasma concentration	Time to maximum plasma concentration [Tmax]) after single and multiple doses at defined timepoints in the combination regimen	Up to 18 months
Secondary	Immunogenicity of danvatirsen	Anti-danvatirsen antibody titers at defined timepoints in the combination regimen	Up to 18 months