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.

Tracking Information

• First Submitted Date: March 10, 2020
• First Posted Date: March 12, 2020
• Last Update Posted Date: January 12, 2024
• Actual Study Start Date: December 21, 2020
• Estimated Primary Completion Date: June 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 10, 2024)

• 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
• 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
• 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

Original Primary Outcome Measures (submitted: March 11, 2020)

• Characterize the safety and tolerability of ASP-1929 PIT treatment in combination with anti-PD1 treatment [ Time Frame: 24 months ]
  Treatment Emergent Adverse Events (TEAE) and Serious TEAE
• Head & Neck SCC: Assess the effect of ASP-1929 PIT treatment with anti-PD1 therapy on tumor response [ Time Frame: 24 months ]
  Objective Response Rate (ORR) defined as the proportion of patients with confirmed overall tumor response of complete response (CR) or partial response (PR) per modified RECIST 1.1, as assessed by investigator
• Cutaneous SCC: Assess the effect of ASP-1929 PIT treatment with anti-PD1 therapy on tumor response [ Time Frame: 24 months ]
  Objective Response Rate (ORR) defined as the proportion of patients with confirmed overall tumor response of complete response (CR) or partial response (PR) per modified RECIST 1.1, as assessed by investigator and central review of tumor imaging by photography and radiographic assessments

Current Secondary Outcome Measures (submitted: January 10, 2024)

• Overall Survival (OS) [ Time Frame: 24 months ]
  Assess the effect of ASP-1929 PIT treatment in combination with anti-PD1 therapy on survival
• Progression-free survival (PFS) [ Time Frame: 24 months ]
  Assess the effect of ASP-1929 PIT treatment in combination with anti-PD1 therapy on survival
• Duration of Response (DOR) [ Time Frame: 24 months ]
  Assess the effect of ASP-1929 PIT treatment in combination with anti-PD1 therapy on survival
• 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

Original Secondary Outcome Measures (submitted: March 11, 2020)

• Overall Survival (OS) defined as the time from first dose of study treatment until death due to any cause [ Time Frame: 24 months ]
  Assess the effect of ASP-1929 PIT treatment in combination with anti-PD1 therapy on survival
• Progression-free survival (PFS) defined as the time from first dose of study treatment until disease progression per modified RECIST 1.1 or death [ Time Frame: 24 months ]
  Assess the effect of ASP-1929 PIT treatment in combination with anti-PD1 therapy on survival
• Duration of Response (DOR) defined as the time from first response (CR or PR) to the time of disease progression (PD) per modified RECIST 1.1 [ Time Frame: 24 months ]
  Assess the effect of ASP-1929 PIT treatment in combination with anti-PD1 therapy on survival

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: An Open-label Study Using ASP-1929 Photoimmunotherapy in Combination With Anti-PD1 Therapy in EGFR Expressing Advanced Solid Tumors
• Official Title: An Open-label Study Using ASP-1929 Photoimmunotherapy in Combination With Anti-PD1 Therapy in EGFR Expressing Advanced Solid Tumors
• 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.
• 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
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: Single (Outcomes Assessor); Primary Purpose: Treatment

Condition

• 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

Intervention

• Biological: 200 mg Pembrolizumab
  every 3 weeks on Days 1 and 22 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.
• 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.

Study Arms

• Cohort 1- 1L HNSCC
  Recurrent locally advanced and/or metastatic head and neck squamous cell carcinoma
  Interventions:

  • Biological: 200 mg Pembrolizumab
  • Combination Product: ASP-1929
• Cohort 2- 1L cuSCC
  Locally advanced or metastatic cutaneous squamous cell carcinoma
  Interventions:

  • Biological: 350 mg Cemiplimab
  • Combination Product: ASP-1929
• Cohort 3- 2L cuSCC
  Locally advanced or metastatic cutaneous squamous cell carcinoma
  Interventions:

  • Biological: 350 mg Cemiplimab
  • Combination Product: ASP-1929

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Estimated Enrollment (submitted: October 27, 2020): 74
• Original Estimated Enrollment (submitted: March 11, 2020): 54
• Estimated Study Completion Date: June 2025
• Estimated Primary Completion Date: June 2024 (Final data collection date for primary outcome measure)

Eligibility 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04305795
• Other Study ID Numbers: ASP-1929-181
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• 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

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Rakuten Medical, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Rakuten Medical, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

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

• PRS Account: Rakuten Medical, Inc.
• Verification Date: January 2024