Study of SIRPant-M in Participants With Relapsed or Refractory Non-Hodgkin's Lymphoma

NCT05967416 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: SIRP01-1001
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 3

Brief Summary

The goal of this study is to test SIRPant-M (RB-1355) , an autologous cell therapy, alone or in combination with focal external-beam radiotherapy in participants with relapsed or refractory non-Hodgkin's lymphoma (NHL). Two dose levels of SIRPant-M are being tested. The main question this study aims to answer is if SIRPant-M alone or in combination with radiotherapy is safe and well-tolerated.

Conditions

Refractory Non-Hodgkin Lymphoma; Relapsed Non-Hodgkin Lymphoma

Keywords

Non-Hodgkin Lymphoma; Relapsed/Refractory Non-Hodgkin Lymphoma; Autologous cell therapy

Outcome Measures

Primary Outcomes (1)

• Incidence of treatment emergent adverse events (TEAEs) and adverse events (AEs)

  Includes evaluation of frequency and severity of AEs, serious adverse events (SAEs), TEAEs, and adverse events of special interest (AESIs), including injection site reactions and abnormalities in clinical laboratory assessments, vital signs, or physical examination findings. Graded according to Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0.

  Day -42 through Day 364

Secondary Outcomes (2)

• Recommended phase 2 dose of autologous SIRPant-M +/- 2.5 Gy ×3 focal XRT

  Day 1 through Day 364

• Objective response rate (ORR)

  Day 1 through Day 364

Study Arms (6)

SIRPant-M (90×10^6 cells)

EXPERIMENTAL

SIRPant-M Monotherapy (Single Agent)

Biological: SIRPant-M

SIRPant-M (90×10^6 cells) with focal XRT

EXPERIMENTAL

SIRPant-M coupled with 2.5 Gy of focal XRT administered within 24 hours after the first ITI and within 3 hours before to 24 hours after the second and third ITI

Biological: SIRPant-M; Radiation: External-beam radiotherapy (XRT)

SIRPant-M (300×10^6 cells)

EXPERIMENTAL

SIRPant-M Monotherapy (Single Agent)

Biological: SIRPant-M

SIRPant-M (300×10^6 cells) with focal XRT

EXPERIMENTAL

SIRPant-M coupled with 2.5 Gy of focal XRT administered within 24 hours after the first ITI and within 3 hours before to 24 hours after the second and third ITI

Biological: SIRPant-M; Radiation: External-beam radiotherapy (XRT)

SIRPant-M (600×10^6 cells) with focal XRT, alternate Day 1, 3, 5 IT-dosing

EXPERIMENTAL

SIRPant-M coupled with 2.5 Gy of focal XRT administered within 24 hours after the first ITI and within 3 hours before to 24 hours after the second and third ITI

Biological: SIRPant-M; Radiation: External-beam radiotherapy (XRT)

SIRPant-M (600×10^6 cells) coupled with focal XRT, weekly (W1, 2, 3) IT-dosing

EXPERIMENTAL

SIRPant-M coupled with 2.5 Gy of focal XRT administered within 24 hours after the first ITI and within 3 hours before to 24 hours after the second and third ITI

Biological: SIRPant-M; Radiation: External-beam radiotherapy (XRT)

Interventions

SIRPant-M BIOLOGICAL

Autologous activated macrophage cell therapy manufactured from peripheral blood mononuclear cells given by intratumoral injection

SIRPant-M (300×10^6 cells); SIRPant-M (300×10^6 cells) with focal XRT; SIRPant-M (600×10^6 cells) coupled with focal XRT, weekly (W1, 2, 3) IT-dosing; SIRPant-M (600×10^6 cells) with focal XRT, alternate Day 1, 3, 5 IT-dosing; SIRPant-M (90×10^6 cells); SIRPant-M (90×10^6 cells) with focal XRT

External-beam radiotherapy (XRT) RADIATION

Radiotherapy given by external beam to the IT-injected lesion only

SIRPant-M (300×10^6 cells) with focal XRT; SIRPant-M (600×10^6 cells) coupled with focal XRT, weekly (W1, 2, 3) IT-dosing; SIRPant-M (600×10^6 cells) with focal XRT, alternate Day 1, 3, 5 IT-dosing; SIRPant-M (90×10^6 cells) with focal XRT

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult, defined as age ≥ 18 (at screening), who are willing and able to provide informed consent
• Must have relapsed/refractory lymphoma, received at least 2 lines of systemic therapy, be ineligible or inappropriate for other treatment regimens known to have curative potential, and must have recovered from the acute toxic effects of all prior oncologic therapy of curative intent (except alopecia)
• Histologically or cytologically confirmed diagnosis of NHL, any one of the below:
• Eligible for SIRPant-M monotherapy or SIRPant-M plus focal XRT combination therapy: Diffuse large B-cell lymphoma and cutaneous T-cell lymphoma (CTCL), including mycosis fungoides (MF), Sezary Syndrome, anaplastic large cell lymphoma (ALCL), lymphomatoid papulosis; adult T-cell leukemia/lymphoma (ATLL); peripheral T cell lymphoma; and angioimmunoblastic T cell lymphoma
• Eligible for SIRPant-M monotherapy only: Cutaneous B-cell lymphoma, including primary cutaneous follicle center lymphoma and primary cutaneous marginal zone B-cell, leg type; follicular center lymphoma; chronic lymphocytic leukemia (CLL) /small lymphocytic lymphoma (SLL); mantle cell lymphoma (MCL); nodal marginal zone B-cell lymphoma
• Must have at least one accessible lymph node or cutaneous or subcutaneous lesion of 1.5 to 5 cm in one dimension as measured by computed tomography (CT) or positron emission tomography/computed tomography (PET/CT) or ultrasound for ITI by an interventional radiologist or other appropriately qualified and trained personnel, which presents a low risk for complications as determined by the Interventional Radiologist and the Principal Investigator. The target lesion must not have been previously irradiated. Note that lesions in the vicinity of large vessels, and tumor-encased large vessels are not considered low-risk. Additional caution should be taken in patients with neck lesions and lesions connected to ulcerated skin or mucosal surface. The target lesion must not be \>5 cm in any dimension.
• Must have a life expectancy \> 3 months; must also be confirmed within 7 days prior to Day 1 of SIRPant-M ITI treatment
• Must have an Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2; must also be confirmed within 7 days prior to Day 1 of SIRPant-M ITI treatment
• Must have hematologic values as follows: hemoglobin (Hgb) \> 8 g/dL, ANC \> 500 /mm3, monocyte counts ≥ 200/μL, and platelets \> 50,000/µL; must also be confirmed within 7 days prior to Day 1 of SIRPant-M ITI treatment
• Must have adequate renal and hepatic function as follows:
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \<3× the upper limit of normal (ULN) (unless attributed to leukemic involvement or required concomitant medication)
• Calculated creatinine clearance ≥60 milliliter per minute (mL/min) calculated with Cockcroft-Gault formula
• Bilirubin ≤1.5×ULN, unless secondary to Gilbert's Syndrome.
• Must also be confirmed within 7 days prior to Day 1 of SIRPant-M ITI treatment.
• Cardiac function: Must be American Heart Association (AHA) class 1 without significant limitation of physical activity; must also be confirmed within 7 days prior to Day 1 of SIRPant-M ITI treatment.

You may not qualify if:

• Must not have received prior ITI therapy
• Must not have received ASCT or treatment with cellular therapy including CAR-T within the prior 1 month; must not have received allogeneic stem cell transplantation within prior 6 months and must have no active graft-versus-host disease (GVHD) or be under active immunosuppression for GVHD.
• Must not have received prior systemic anti-cancer therapy within the past 14 days before start of study cell therapy
• Must not have received IL-2 therapy within the last 6 months
• Must not have acquired immune defects such as human immunodeficiency virus (HIV)
• Must not have uncontrolled hypertension (systolic \>180 mmHg, diastolic \>100 mmHg)
• Must not have diagnosis of unclassifiable B cell lymphoma
• Must not have bleeding diathesis or abnormal values for prothrombin time (PT) or activated partial thromboplastin time (aPTT), international normalized ratio (INR) \> 1.5× ULN
• Must not be receiving anti-platelet drugs that may present a risk for intratumor injections
• Must not have pulmonary disease which, in the opinion of the Investigator, might impair the patient's respiratory tolerance to moderate pulmonary fluid overload (eg, interstitial lung disease, severe chronic obstructive pulmonary disease)
• Must not have known alcohol or drug abuse
• Must not have received an investigational agent within the past 30 days before start of study cell therapy
• Must not require a chronic therapy with prednisone at a dose of or exceeding 10 mg/day or equivalent or any other form of immunosuppressive therapy
• Must not have active central nervous system tumors or metastases
• Must not be ineligible to receive 2.5 Gy ×3 focal external-beam radiation therapy as determined by the Radiation Oncologist and Principal Investigator (Cohort 1/Group 2, Cohort 2/Group 4, and Cohort -1/Group 4 only)

Sponsors & Collaborators

• SIRPant Immunotherapeutics, Inc.: lead

Study Sites (3)

City of Hope

Duarte, California, 91010, United States

RECRUITING

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

RECRUITING

MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

MeSH Terms

Conditions

Lymphoma, Non-Hodgkin

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Jelle Kijlstra, MD, MBA

  BobcatBio, p/k/a SIRPant Immunotherapeutics

  STUDY DIRECTOR

Central Study Contacts

Jelle Kijlstra, MD, MBA

CONTACT

206-909-1125; jkijlstra@bobcatbio.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Enrollment will begin with Cohort 1, Group 1 (SIRPant-M monotherapy, low dose). Upon approval from the SRC after Cohort 1, Group 1 review, enrollment in Cohort 1, Group 2 (SIRPant-M coupled with XRT, low dose) and Cohort 2, Group 3 (SIRPant-M monotherapy, intermediate dose) will open. Upon approval from the SRC after Cohort 1, Group 2 and Cohort 2, Group 3 review, enrollment in Cohort 2, Group 4 (SIRPant-M + XRT, intermediate cell dose) will open. Upon further approval from the SRC, Cohort 3, Groups 5 and 6 (high cell dose + XRT, alternate day- versus weekly IT-dosing) will enroll.

Study Record Dates

• First Submitted: July 21, 2023
• First Posted: August 1, 2023
• Study Start: January 17, 2024
• Primary Completion: June 1, 2025
• Study Completion: December 1, 2025
• Last Updated: December 20, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)