Activity and Safety of Danvatirsen and Pembrolizumab in HNSCC

ID#: NCT05814666

Age: 18 years - 66+

Gender: All

Healthy Subjects: No

Study Phase: Phase 2

Recruitment Status: Recruiting

Start Date: December 30, 2023

End Date: August 30, 2025

Contact Information:
Flamingo Therapeutics
+1 484 482 0007
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.

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.