Phase 1b/2, Open-label Study of ASP-1929 Photoimmunotherapy in Combination With Anti-PD1 Therapy in EGFR Expressing Advanced Solid Tumors

• Status: Not yet recruiting
• Trial end date: 2024-06-01
• Target enrollment: 54
• Participant gender: All

Summary

An Open-label Study using ASP-1929 Photoimmunotherapy in Combination with anti-PD1 Therapy in EGFR Expressing Advanced Solid Tumors in patients with head and neck and cutaneous squamous cell carcinoma.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Rakuten Medical, Inc.
• Treatments: Cemiplimab; Pembrolizumab

Criteria

Overall Inclusion Criteria:

Provide written informed consent

• Male or female ≥ 18 years old at the time of signing informed consent

• Measurable disease by modified RECIST 1.1 as assessed by Investigator. Lesions located in a previously irradiated area are considered measurable if progression has been demonstrated. See modified RECIST 1.1 criteria definition for disease progression in applicable subprotocols. Note: The same image acquisitions and processing parameters used at screening should be used throughout the study.

• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at the time of screening

• Life expectancy > 3 months, based on Investigator judgement

• 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)

• Adequate organ function lab values as described below (all screening labs should be performed within 14 days of study Day 1):

Hematology: Adequate bone marrow function as shown by absolute neutrophil count (ANC) ≥1.5 x 109/L, platelets ≥100 x 109/L, hemoglobin (Hb) ≥ 9 g/dL (transfusions and growth factors must not be used within 2 weeks of study day 1 to meet these requirements)

Hepatic: Alkaline phosphatase (ALP) < 2 times upper limit of normal, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 2.5 times the upper limit of normal (≤ 5x ULN for patients with liver metastases), and total serum bilirubin < 2 mg/dL (unless the patient has Gilbert's disease)

Renal: Creatinine clearance (CCr) ≥30 mL/min/1.73 m2 and can be calculated based upon local guidance.

Glomerular filtration rate (GFR) to be calculated per the CKD-EPI equation, expressed as a single equation, is:

GFR = 141 * min(Scr/κ,1)α * max(Scr/κ, 1)-1.209 * 0.993Age * 1.018 [if female] * 1.159 [if black] Note: Scr is serum creatinine (mg/dL), κ is 0.7 for females and 0.9 for males, α is -0.329 for females and -0.411 for males, min indicates the minimum of Scr/κ or 1, and max indicates the maximum of Scr/κ or 1

Coagulation: International Normalized Ratio (INR) or Prothrombin Time (PT) ≤ 1.5x ULN unless patient is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants.

• Female participants 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. Patients of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year

• 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.

Inclusion Criteria for Head & Neck:

• Histologically- or cytologically-confirmed diagnosis of recurrent locally advanced and/or metastatic head and neck squamous cell carcinoma with known PD-L1 expression status

• Primary tumor locations of oropharynx, oral cavity, hypopharynx, or larynx. Patients may not have a primary tumor site of nasopharynx (any histology)

• At least 1 head and neck SCC accessible to light illumination

• Combined Positive Score (CPS) ≥ 1 as determined by an FDA approved test

Inclusion Criteria for Cutaneous:

• Histologically- or cytologically-confirmed and diagnosed locally advanced and/or metastatic-cuSCC with known PD-L1 expression status. LA-cuSCC is defined as tumor not amenable to definitive surgery or radiation due to multiple recurrences, anatomic complexity, or other patient contraindications for therapy.

• At least one cutaneous SCC tumor accessible to light illumination

Overall Exclusion Criteria:

• Prior therapy with an anti-PD1 or anti-PD-L1

• 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 7 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). Replacement therapy (eg, thryroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment

• History of non-infectious pneumonitis that required steroids 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. Note: If participant has had major surgery, they must have recovered adequately from the toxicity and/or complications before study Day 1

• 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

• Any other condition which, in the Investigator's opinion, deems the patient an unsuitable candidate to receive ASP-1929 and/or be exposed to PIT light illumination, and anti-PD1 treatment.

• Unwilling or unable to follow protocol requirements