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RM-1995 Photoimmunotherapy, as Monotherapy or Combined With Pembrolizumab, in Patients With Advanced CuSCC and HNSCC

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ClinicalTrials.gov Identifier: NCT05220748
Recruitment Status : Recruiting
First Posted : February 2, 2022
Last Update Posted : April 7, 2022
Sponsor:
Information provided by (Responsible Party):
Rakuten Medical, Inc.

Brief Summary:
A phase 1a/1b, open-label, RM-1995 drug-dose escalation study designed to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary efficacy of RM-1995 photoimmunotherapy treatment as monotherapy (phase 1a) or combined with pembrolizumab (phase 1b) in patients with cutaneous squamous cell carcinoma (cuSCC) or head and neck squamous cell carcinoma (HNSCC) that has progressed despite all available standard therapies.

Condition or disease Intervention/treatment Phase
Cutaneous Squamous Cell Carcinoma Head and Neck Squamous Cell Carcinoma Combination Product: RM-1995 Biological: Pembrolizumab Phase 1

Detailed Description:

Enrollment consists of six cohorts of patients with locally advanced cuSCC or HNSCC that has recurred or progressed on or after at least one prior line of therapy, which must include prior platinum-based chemotherapy and is not eligible for further locoregional therapy, or with metastatic disease that has recurred or progressed after all available standard therapies. Patients will receive anti-CD25 antibody, conjugated to the light-activatable dye, IRDye® 700DX, followed by illumination with non-thermal red light (RM-1995 photoimmunotherapy)) as monotherapy (phase 1a), or in combination with pembrolizumab (phase 1b).

Patients are required to have measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1,Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2, and a superficial lesion accessible to PIT at the time of screening.

Phase 1a primary objectives are to evaluate the safety and tolerability of RM-1995 photoimmunotherapy treatment as monotherapy and determine the maximum tolerated dose (MTD) or maximum administered dose (MAD).

Phase 1b primary objectives are to evaluate the safety and tolerability of RM-1995 photoimmunotherapy treatment in combination with pembrolizumab and determine the MTD or MAD.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 36 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1 First-in-Human, Drug-dose Escalation Study of RM-1995 Photoimmunotherapy, as Monotherapy or Combined With Pembrolizumab, in Patients With Advanced Cutaneous Squamous Cell Carcinoma or With Head and Neck Squamous Cell Carcinoma
Actual Study Start Date : March 24, 2022
Estimated Primary Completion Date : July 2024
Estimated Study Completion Date : September 2024

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: RM-1995 Photoimmunotherapy (Phase 1a Monotherapy)
Patients with locally advanced cuSCC or HNSCC or metastatic disease that has recurred or progressed, despite all available standard therapies.
Combination Product: RM-1995
RM-1995 will be administered by intravenous (IV) infusion followed approximately 24 hours later by tumor illumination with 690 nm non thermal red light using the PIT690 Laser System. The starting dose of RM-1995 will be 0.25 mg/kg and escalated up to 2.0 mg/kg over 6 dosing cohorts

Active Comparator: RM-1995 Photoimmunotherapy + Pembrolizumab (Phased 1b Combination Therapy)
Patients with locally advanced cuSCC or HNSCC or metastatic disease that has recurred or progressed, despite all available standard therapies.
Combination Product: RM-1995
RM-1995 will be administered by intravenous (IV) infusion followed approximately 24 hours later by tumor illumination with 690 nm non thermal red light using the PIT690 Laser System. The starting dose of RM-1995 will be 0.25 mg/kg and escalated up to 2.0 mg/kg over 6 dosing cohorts

Biological: Pembrolizumab
Pembrolizumab (200 mg) will be administered by intravenous (IV) infusion one week before the RM-1995 PIT treatment for patients in the combination arm. Once the DLT window is compete, pembrolizumab dosage will be maintained at either 200 mg Q3w, or shift to 400 mg Q6w, per investigator discretion.




Primary Outcome Measures :
  1. Phase 1a Monotherapy: Evaluate the safety and tolerability of RM-1995 PIT treatment, and determine the Maximum Tolerated Dose (MTD) or Maximum Administered Dose (MAD). [ Time Frame: 28 months ]
    Evaluate the safety and tolerability of RM-1995 photoimmunotherapy treatment, and determine the MTD or MAD

  2. Phase 1b Combination Therapy: Evaluate the safety and tolerability of RM-1995 PIT treatment in combination with pembrolizumab and determine the MTD or MAD. [ Time Frame: 28 months ]
    Evaluate the safety and tolerability of RM-1995 photoimmunotherapy treatment in combination with pembrolizumab and determine the MTD or MAD.


Secondary Outcome Measures :
  1. Serum concentration of RM-1995. [ Time Frame: Various timepoints from Cycles 1, 2, and 3, Day 1 through Day 21. Each cycle is 21 days. ]
  2. Serum concentration of total antibody. [ Time Frame: Various timepoints from Cycles 1, 2, and 3, Day 1 through Day 21. Each cycle is 21 days. ]
  3. Serum concentration of IR-700. [ Time Frame: Various timepoints from Cycles 1, 2, and 3, Day 1 through Day 21. Each cycle is 21 days. ]
  4. Assess antitumor activity of RM-1995. [ Time Frame: 28 months ]
    Conduct a preliminary assessment of antitumor activity following RM-1995 PIT treatment as monotherapy or in combination therapy with pembrolizumab, using Objective Response Rate (ORR) as a measurement of anti-tumor activity.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria
  • Inclusion Criteria. Patients must meet all the following criteria to be eligible to participate in the study:
  • Patient must be at least 18 years old.
  • Patient must have tumor types of head and neck squamous cell carcinoma (HNSCC), cutaneous squamous cell carcinoma (cuSCC)
  • Locally advanced or locoregional disease that has recurred or progressed on or after at least one prior line of therapy, which must include prior platinum-based chemotherapy, and is not eligible for further locoregional treatment (ie, standard surgery or radiation), or for which locoregional treatment has proved to be intolerable or is medically contraindicated.
  • Metastatic disease that has recurred or progressed following prior platinum-based chemotherapy, prior immunotherapy with PD-(L)1 inhibitors, or other standard of care systemic treatment, has proven to be ineffective, intolerable, or is considered medically contraindicated in the opinion of the Investigator
  • Patient must have tumors with at least one superficial lesion of the skin or oral cavity, not deeper than 1 cm and that is accessible for photoimmunotherapy treatment. Note: Lesions that are in the pharynx and larynx will not be included in the treatment.
  • Patient must have the ability to provide representative tumor specimens with an associated pathology report.
  • Patient must have measurable disease by RECIST 1.1 as assessed by Investigator.
  • Patient must have ECOG performance status of 0 to 2 at the time of screening
  • Patient has life expectancy ≥ 3 months based on Investigator's judgement.
  • Adequate organ function laboratory values (Hematology, Hepatic, Renal and Coagulation).
  • Female patients of childbearing potential must not be pregnant or breastfeeding and must be willing to use 2 methods of highly effective birth control, or practice abstinence throughout the study and for at least 120 days after the last dose of study medication.
  • Male patients must be sterile or agree to use an adequate method of contraception or practice abstinence starting with the first dose of study medication and for at least 120 days after the last dose of study medication.

Exclusion Criteria. Patients who meet any of the criteria below will be ineligible to participate in the study:

  • Receiving any other investigational agents, approved anticancer therapies, including chemotherapy, hormonal therapy, ultraviolet-light therapy, or other topical therapy within 2 weeks or 5 half-lives, whichever is longer, before initiation of study treatment, with the following exceptions:
  • Hormone-replacement therapy or oral contraceptives
  • Herbal therapy, including herbal therapy intended as anticancer therapy and medicinal cannabinoids taken to reduce symptom burden, must be discontinued at least 1 week before the first dose of pembrolizumab (combination therapy) or the first dose of RM 1995 (monotherapy)
  • Palliative radiotherapy for painful boney metastases or metastases in potentially sensitive locations (eg, epidural space) must be completed > 2 weeks before the first dose of pembrolizumab (combination therapy) or the first dose of RM 1995 (monotherapy)
  • Previously initiated bisphosphonate or denosumab therapy for bone metastases may be continued during study participation.
  • Treated with local radiation therapy within 12 weeks before the first dose of study treatment. Patients must have recovered from all radiation-related toxicities to Grade < 1 or baseline and must not require steroids.
  • Treatment with systemic immunostimulatory agents not described above (including but not limited to IFN-α, IL-2) within 6 weeks or 5 half-lives of the drug, whichever is shorter, before the first dose of study treatment.
  • Adverse events from prior anticancer therapy that have not resolved to Grade ≤ 1, except for alopecia or endocrinopathy managed with replacement therapy.
  • Patients who have tumors at sites that may compromise sensitive and vital anatomic structures.
  • Malignancies other than disease under study within 3 years prior to treatment start, except for those with a negligible risk of metastasis or death.
  • Significant cardiovascular disease, such as New York Heart Association cardiac disease (Class II or greater), myocardial infarction within the previous 3 months, unstable arrhythmias, or unstable angina.
  • Known clinically significant liver disease, including active viral, alcoholic, or other hepatitis, cirrhosis, or inherited liver disease.
  • Prior allogeneic bone marrow transplantation or prior solid organ transplantation.
  • Known history of testing positive for human immunodeficiency virus or acquired immunodeficiency syndrome -related illness.
  • Known infection or detection of active Hepatitis B (e.g., HBsAg positive), Hepatitis C (eg, RNA [qualitative]), or SARS-CoV-2 (qualitative).
  • Received a live, attenuated vaccine within 4 weeks before the first dose of study treatment or anticipating the receipt of a required live, attenuated vaccine during the study (based on known medical history).
  • Receiving drugs known to prolong the QTc interval while on study treatment or within 14 days before the first dose of study treatment.
  • Receiving cytochrome P450 (CYP) substrates, inhibitors, inducers while on study treatment or within 14 days before the first dose of study treatment.
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or poorly controlled psychiatric illness.
  • Received oral or IV antibiotics within 2 weeks before the first dose of study treatment
  • Major surgery or significant traumatic injury within 28 days before the first dose of study treatment or anticipation of the need for major surgery that is unrelated to study intervention during the study.
  • History of severe allergic, anaphylactic, or other hypersensitivity reactions to any of the components of RM-1995 or to other recombinant chimeric, human, or humanized antibodies.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05220748


Contacts
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Contact: Bogdan Veresh, MD, MSc 858-207-3113 clinicaltrialinfo@rakuten-med.com

Locations
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United States, California
City of Hope National Medical Center Not yet recruiting
Duarte, California, United States, 91010
Contact: Victoria Villaflor, MD         
Principal Investigator: Victoria Villaflow, MD         
UCSD Head and Neck Oncology Not yet recruiting
La Jolla, California, United States, 92093
Contact: Charles Coffey         
Principal Investigator: Charles Coffey, MD         
UCSF Helen Diller Family Comprehensive Cancer Center Not yet recruiting
San Francisco, California, United States, 94115
Contact: Hyunseok Kang         
Principal Investigator: Hyunseok Kang, MD         
United States, Kentucky
Univeristy of Kentucky Not yet recruiting
Lexington, Kentucky, United States, 40506
Contact: Joseph Valentino, MD         
Principal Investigator: Joseph Valentino, MD         
United States, Pennsylvania
Thomas Jefferson University Recruiting
Philadelphia, Pennsylvania, United States, 19107
Contact: David Cognetti         
Principal Investigator: David Cognetti, MD         
United States, Texas
MD Anderson Cancer Center Not yet recruiting
Houston, Texas, United States, 77030
Contact: Ann Gillenwater         
Principal Investigator: Ann Gillenwater, MD         
Sponsors and Collaborators
Rakuten Medical, Inc.
Investigators
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Study Chair: Bogdan Veresh Rakuten Medical, Inc.
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Responsible Party: Rakuten Medical, Inc.
ClinicalTrials.gov Identifier: NCT05220748    
Other Study ID Numbers: RM-1995-101
First Posted: February 2, 2022    Key Record Dates
Last Update Posted: April 7, 2022
Last Verified: April 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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
RM-1995
RM-1995-101
HNSCC
CUSCC
head and neck squamous cell carcinoma
cutaneous squamous cell carcinoma
PIT
photoimmunotherapy
skin cancer
skin
head and neck cancer
Additional relevant MeSH terms:
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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
Antineoplastic Agents, Immunological
Antineoplastic Agents