An Open-label Study Using ASP-1929 Photoimmunotherapy in Combination With Anti-PD1 Therapy in EGFR Expressing Advanced Solid Tumors

Open-label study using ASP-1929 photoimmunotherapy in combination with anti-PD1 therapy in patients with recurrent or metastatic head and neck and squamous cell cancer or advanced or metastatic cutaneous squamous cell carcinoma.

Study Overview

• Status: Active, not recruiting
• Conditions: Recurrent Head and Neck Squamous Cell Carcinoma; Metastatic Head-and-neck Squamous-cell Carcinoma; Metastatic Cutaneous Squamous Cell Carcinoma; Locally Advanced Cutaneous Squamous Cell Carcinoma
• Intervention / Treatment: Biological: 200 mg Pembrolizumab; Combination product: ASP-1929; Biological: 350 mg Cemiplimab

Detailed Description

Cohorts of patients with recurrent or metastatic (R/M) squamous cell cancer of the head and neck (HNSCC) or advanced or metastatic cutaneous squamous cell carcinoma (cuSCC) will receive anti-PD1 therapy in combination with anti EGFR antibody-dye conjugate, ASP-1929, followed by photoimmunotherapy (PIT). HNSCC patients are required to have positive expression of programmed cell death ligand 1 (PD-L1) defined by Combined Positive Score (CPS) ≥1. Primary endpoints are safety, tolerability, and tumor response of ASP-1929 PIT treatment in combination with anti-PD1.

• Study Type: Interventional
• Enrollment (Estimated): 74
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Naomi Schechter; Phone Number: 833-725-8633; Email: clinicaltrialinfo@rakuten-med.com
• Study Contact Backup: Name: Ashok Srivatasava; Phone Number: 858-925-5619; Email: clinicaltrialinfo@rakuten-med.com

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami Hospital and Clinics
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • University of Kentucky
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • Oregon
    • Portland, Oregon, United States, 97213
      • Providence Medical Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Vanderbilt-Ingram Cancer Center
  • Texas
    • Houston, Texas, United States, 77030
      • University of Texas, MD Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Overall Inclusion Criteria:

Provide written informed consent

• Cancers as follows:

Cohort 1 : Histologically or cytologically confirmed recurrent locally and/or metastatic head and neck squamous cell carcinoma with Combined Positive Score (CPS) ≥ 1 as determined by a CLIA certified and/or FDA approved test.

Note: A multi-disciplinary group (including a surgeon and radiation oncologist) must agree that the patient is not a candidate for locoregional therapy.

Cohort 2 : Histologically or cytologically confirmed locally advanced or metastatic cutaneous squamous cell carcinoma not amenable to definitive surgery or radiation.

Cohort 3: Histologically or cytologically confirmed locally advanced or metastatic cutaneous squamous cell carcinoma not amendable to definitive surgery or radiation.

• At least one site of disease accessible to light illumination.
• Measurable disease by modified RECIST 1.1.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• No prior systemic therapy administered in the recurrent and/or metastatic setting (with the exception of systemic therapy completed ≥ 6 months prior if given as part of multimodal treatment for locally advanced disease). (Cohort 1 only).
• Patients must be actively receiving single-agent, systemic anti-PD1 therapy at the time of screening (Cohort 3 only).
• Disease progression despite at least 2 months of anti-PD1 therapy at the time of screening. Progression must be confirmed by at least two scans at least one month apart. Screening scan may serve as confirmation of progression (Cohort 3 only).
• Adequate organ function.
• Female patients of childbearing potential must have a negative pregnancy test at screening and must be willing to use 2 methods of highly effective birth control while on study or be surgically sterile, or abstain from heterosexual sexual activity for the course of the study through 120 days after the last dose of anti-PD1 treatment.
• Male participants must agree to use a highly effective method of contraception starting with the first dose of study medication through 120 days after the last dose of anti-PD1 treatment.

Exclusion Criteria:

• Prior therapy with an anti-PD1 or anti-PD-L1 (Cohort 1 only).
• Prior systemic therapy that is not intended as part of definitive treatment (eg, induction, concurrent, adjuvant, or neoadjuvant treatment) (Cohorts 1 and 2 only).
• Systemic anti-PD-1 therapy prior to current course of definitive therapy (Cohort 3 only).
• Prior systemic therapy given as definitive treatment (chemotherapy, EGFR inhibition). Patients with a history of prior chemoradiation are eligible (Cohort 3 only).
• Radiation therapy (or other non-systemic therapy) within 4 weeks prior to study Day 1 or not fully recovered from adverse events due to a previously administered treatment
• Receiving chronic systemic steroid therapy (in doses exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 14 days prior to Cycle 1 Day 1.
• Diagnosed and/or treated for additional malignancy within 2 years prior to study Day 1, except for, curatively treated basal cell carcinoma of the skin, squamous cell carcinoma of the skin and/or curatively resected in situ cervical and/or breast cancers.
• History of significant (≥ Grade 3) cetuximab infusion reactions.
• Prior allogeneic tissue/solid organ transplant.
• Known or active central nervous system metastases and/or carcinomatous meningitis.
• Active autoimmune disease that has required systemic treatment in past 2 years (ie, with use of disease modifying agents, corticosteroids, or immunosuppressive drugs).
• Evidence of interstitial lung disease or current active, noninfectious pneumonitis.
• Active infection requiring systemic therapy.
• Known or active bacterial, viral, and fungal infection including tuberculosis, active Hepatitis B (eg, HBsAg reactive), or Hepatitis C (eg, RNA [qualitative] is detected)
• Known history of testing positive for human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness.
• Received a live vaccine within 30 days of study Day 1. Note: seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (eg, Flu-Mist®) are live attenuated vaccines, and are not allowed.
• Requiring future examinations or treatments within 4 weeks after an ASP-1929 PIT treatment cycle exposing the patient to significant light (eg, eye examinations, surgical procedures, endoscopy) that is unrelated to the ASP-1929 PIT treatment
• Patients expecting to breastfeed during the study and through 120 days after the last dose of study treatment.
• Major surgery or significant traumatic injury ≤ 28 days before study day 1, or anticipation of the need for major surgery during the course of study treatment.
• Currently participating or participated in a study of an investigational agent and received study therapy (including RM-1929 or ASP-1929 PIT studies), or used an investigational device within 4 weeks of study Day 1.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Cohort 1- 1L HNSCC; Recurrent locally advanced and/or metastatic head and neck squamous cell carcinoma	Biological: 200 mg Pembrolizumab; every 3 weeks on Days 1 and 22 of each 6-week cycle for up to 24 months.; Combination product: ASP-1929; ASP-1929 IV on Day 8 of each 6-week cycle for up to 24 months. Photoimmunotherapy Light Treatment on Day 9 of each 6-week cycle for up to 24 months.
Other: Cohort 2- 1L cuSCC; Locally advanced or metastatic cutaneous squamous cell carcinoma	Combination product: ASP-1929; ASP-1929 IV on Day 8 of each 6-week cycle for up to 24 months. Photoimmunotherapy Light Treatment on Day 9 of each 6-week cycle for up to 24 months.; Biological: 350 mg Cemiplimab; every 3 weeks on Days 1 and 22 of each 6-week cycle for up to 24 months.
Other: Cohort 3- 2L cuSCC; Locally advanced or metastatic cutaneous squamous cell carcinoma	Combination product: ASP-1929; ASP-1929 IV on Day 8 of each 6-week cycle for up to 24 months. Photoimmunotherapy Light Treatment on Day 9 of each 6-week cycle for up to 24 months.; Biological: 350 mg Cemiplimab; every 3 weeks on Days 1 and 22 of each 6-week cycle for up to 24 months.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Characterize the safety and tolerability of ASP-1929 PIT treatment in combination with anti-PD1 therapy	Treatment Emergent Adverse Events (TEAE) and Serious TEAE	24 months
HNSCC: Assess the effect of ASP-1929 PIT treatment with anti-PD1 therapy on tumor response	Objective Response Rate (ORR) per modified RECIST 1.1, as assessed by investigator	24 months
cuSCC: Assess the effect of ASP-1929 PIT treatment with anti-PD1 therapy on tumor response	Objective Response Rate (ORR) per modified RECIST 1.1, by central review of tumor imaging by photography and radiographic assessments	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	Assess the effect of ASP-1929 PIT treatment in combination with anti-PD1 therapy on survival	24 months
Progression-free survival (PFS)	Assess the effect of ASP-1929 PIT treatment in combination with anti-PD1 therapy on survival	24 months
Duration of Response (DOR)	Assess the effect of ASP-1929 PIT treatment in combination with anti-PD1 therapy on survival	24 months
cuSCC: Objective Response Rate (ORR) per modified RECIST 1.1, as assessed by investigator review of tumor imaging by photography and radiographic assessments	Assess the effect of ASP-1929 PIT treatment in combination with anti-PD1 therapy on tumor response	24 months

Collaborators and Investigators

• Sponsor: Rakuten Medical, Inc.
• Investigators: Study Director: Naomi Schechter, MD, Rakuten Medical, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): December 21, 2020
• Primary Completion (Estimated): June 1, 2024
• Study Completion (Estimated): June 1, 2025

Study Registration Dates

• First Submitted: March 10, 2020
• First Submitted That Met QC Criteria: March 11, 2020
• First Posted (Actual): March 12, 2020

Study Record Updates

• Last Update Posted (Actual): January 12, 2024
• Last Update Submitted That Met QC Criteria: January 10, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: skin; Pembrolizumab; EGFR; HNSCC; head and neck; squamous cell carcinoma; Anti-PD1; cutaneous; Cemiplimab; Rakuten Medical; ASP-1929; PIT; CUSCC; photoimmunotherapy
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Head and Neck Neoplasms; Neoplasms, Squamous Cell; Carcinoma; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Pembrolizumab; Cemiplimab
• Other Study ID Numbers: ASP-1929-181

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: Yes