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

• ClinicalTrials.gov Identifier: NCT04305795
• Recruitment Status: Active, not recruiting
• First Posted: March 12, 2020
• Last Update Posted: January 12, 2024
• Sponsor: Rakuten Medical, Inc.
• Information provided by (Responsible Party): Rakuten Medical, Inc.

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Recurrent Head and Neck Squamous Cell Carcinoma; Metastatic Head-and-neck Squamous-cell Carcinoma; Locally Advanced Cutaneous Squamous Cell Carcinoma; Metastatic Cutaneous Squamous Cell Carcinoma	Biological: 200 mg Pembrolizumab; Biological: 350 mg Cemiplimab; Combination Product: ASP-1929	Phase 1; Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 74 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: An Open-label Study Using ASP-1929 Photoimmunotherapy in Combination With Anti-PD1 Therapy in EGFR Expressing Advanced Solid Tumors
• Actual Study Start Date: December 21, 2020
• Estimated Primary Completion Date: June 2024
• Estimated Study Completion Date: June 2025

Arms and Interventions

Arm	Intervention/treatment
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.
Cohort 2- 1L cuSCC; Locally advanced or metastatic cutaneous squamous cell carcinoma	Biological: 350 mg Cemiplimab; 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.
Cohort 3- 2L cuSCC; Locally advanced or metastatic cutaneous squamous cell carcinoma	Biological: 350 mg Cemiplimab; 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.

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

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

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Locations

United States, Florida

University of Miami Hospital and Clinics

Miami, Florida, United States, 33136

United States, Kentucky

University of Kentucky

Lexington, Kentucky, United States, 40536

United States, Minnesota

Mayo Clinic

Rochester, Minnesota, United States, 55905

United States, Oregon

Providence Medical Center

Portland, Oregon, United States, 97213

United States, Pennsylvania

Thomas Jefferson University

Philadelphia, Pennsylvania, United States, 19107

United States, Tennessee

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, United States, 37203

United States, Texas

University of Texas, MD Anderson Cancer Center

Houston, Texas, United States, 77030

Sponsors and Collaborators

Rakuten Medical, Inc.

Investigators

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

More Information

• Responsible Party: Rakuten Medical, Inc.
• ClinicalTrials.gov Identifier: NCT04305795
• Other Study ID Numbers: ASP-1929-181
• First Posted: March 12, 2020
• Last Update Posted: January 12, 2024
• Last Verified: January 2024

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: Yes
• Device Product Not Approved or Cleared by U.S. FDA: Yes

Keywords provided by Rakuten Medical, Inc.:

Rakuten Medical; ASP-1929; HNSCC; CUSCC; head and neck; cutaneous; squamous cell carcinoma; photoimmunotherapy; PIT; skin; EGFR; Anti-PD1; Pembrolizumab; Cemiplimab

Additional relevant MeSH terms:

Carcinoma; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Squamous Cell; Head and Neck Neoplasms; Neoplasms by Site; Pembrolizumab; Cemiplimab; Antineoplastic Agents, Immunological; Antineoplastic Agents; Immune Checkpoint Inhibitors; Molecular Mechanisms of Pharmacological Action