A Study of OR502, a Monoclonal Antibody Targeting LILRB2, Alone and in Combination With Anticancer Agents

NCT06090266 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: OR502-101
• Study Type: interventional
• Target: 168
• Locations: 1 country
• Sites: 4

Brief Summary

This is an open-label, multicenter, first-in-human dose-escalation and expansion Phase 1-2 study designed to determine the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary anti-tumor activity of OR502 administered as a monotherapy and in combination with cemiplimab in subjects with advanced solid tumors.

Conditions

Cancer; Tumor, Solid; Malignant Neoplasm; Metastatic Cancer; Advanced Solid Tumor; Cutaneous Melanoma; Non-small Cell Lung Cancer

Outcome Measures

Primary Outcomes (4)

• Dose-limiting Toxicity

  The incidence of DLTs during the DLT assessment period.

  First 21 days of treatment.

• Adverse Events and Serious Adverse Events

  The nature, frequency, and severity of adverse events and serious adverse events graded by CTCAE v 5.0 as aggregated descriptive findings.

  Screening to 90 days from last dose.

• Vital Signs

  Assessment of changes in vital sign measurements (heart rate, pulse oximetry and blood pressure) as aggregated descriptive findings.

  Screening to 90 days from last dose.

• Recommended Dose and Regimen (mono and combination therapy)

  Determination of the recommended dose of OR502 for further development.

  Screening to 90 days from last dose.

Secondary Outcomes (5)

• Pharmacokinetics of OR502

  Day 1 of dosing through 21 days post last dose.

• Pharmacokinetics of OR502

  Day 1 of dosing through 21 days post last dose.

• Objective Response Rate (ORR)

  Day 1 of dosing through 90 days after the last dose.

• Disease Control Rate (DCR)

  Day 1 of dosing through 90 days after the last dose.

• Progression Free Survival (PFS)

  Day 1 of dosing through 90 days after the last dose.

Study Arms (2)

OR502 monotherapy and combination therapy dose-escalation phase (Part A)

EXPERIMENTAL

Escalating repeated doses of OR502 by IV administration as monotherapy or in combination with cemiplimab in subjects with advanced solid tumors. OR502 will be administered once every 3 weeks (Q3W). Cemiplimab will be administered as an IV infusion at a dose of 350 mg.

Drug: OR502; Drug: Cemiplimab

OR502 monotherapy and combination therapy dose-expansion phase (Part B)

EXPERIMENTAL

OR502 administered IV at 2 different dose levels identified in Part A as monotherapy or in combination with cemiplimab in subjects with platinum-resistant ovarian cancer and cutaneous squamous cell carcinoma. Cemiplimab will be administered as an IV infusion at a dose of 350 mg.

Drug: OR502; Drug: Cemiplimab

Interventions

OR502 DRUG

IgG1 monoclonal antibody that binds specifically to the LILRB2 protein.

OR502 monotherapy and combination therapy dose-escalation phase (Part A); OR502 monotherapy and combination therapy dose-expansion phase (Part B)

Cemiplimab DRUG

IgG4 mAb that binds to PD-1 and blocks its interaction with PD-L1 and PD-L2.

OR502 monotherapy and combination therapy dose-escalation phase (Part A); OR502 monotherapy and combination therapy dose-expansion phase (Part B)

Eligibility Criteria

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

You may qualify if:

• Informed consent signed by the subject prior to conducting study-specific procedures.
• Male or female subjects ≥ 18 years of age.
• Histological diagnosis as follows:
• Parts A and B (Cohorts A1, A2, and B1): subjects must have a histological diagnosis of any type of carcinoma, sarcoma, or melanoma with progressive metastatic disease, or progressive locally advanced disease not amenable to local therapy with curative intent.
• Part B (Expansion Cohorts B2-B3): subjects must have a histological diagnosis of the relevant tumor type (CSCC or PROC) with advanced/metastatic disease not amenable to local therapy with curative intent.
• Prior therapies:
• a. Part A (dose-escalation) and Cohort B1 (monotherapy expansion) i. Subjects must have experienced progressive disease (PD) on an established standard systemic anti-cancer therapy for a given tumor type or have been intolerant to such therapy, or in the opinion of the Investigator have been considered ineligible for a particular form of standard therapy on medical grounds. Subjects must have no available proven curative or life prolonging therapies.
• b. Cohorts B4 and B5 (mini-expansion cohorts) i. Subjects must have received a PD-(L)1 inhibitor-based therapy, either alone or in combination with other anti-cancer agents, for at least 12 weeks. If subjects have received other lines of immunotherapy, including PD-(L)1-based therapy, they must have demonstrated clinical benefit on each prior immunotherapy. Subjects may also have received additional anti-cancer therapies after failure of a PD-(L)1 inhibitor, but 2nd line subjects are preferred.
• c. Cohorts B2 and B3 (dose-expansion) i. Cohort B2 subjects (CSCC) must have received a PD-(L)1 inhibitor. Subjects may not have received an additional immunotherapy.
• ii. Cohort B3 subjects (PROC) must have received platinum-based therapy and experienced disease progression on or within 6 months of completion of such therapy. Subjects may have received prior anti-PD-1 therapy. Subjects may have received additional therapies after failure of platinum-based therapy.
• Subjects must have measurable disease per RECIST v1.1.
• People of childbearing potential, if not postmenopausal (defined as no menses for at least 12 continuous months prior to study entry) or surgically sterile, must be willing to practice at least one of the highly effective methods of birth control described in Section 4.3 for at least a menstrual cycle (or partner's menstrual cycle, for male subjects) before and for 4 months after study medication administration.
• Resolution of prior clinically significant therapy-related AEs (excluding alopecia and ≤ Grade 2 peripheral neuropathy) to ≤ Grade 1 per NCI-CTCAE version 5.0, and no treatment for these AEs for at least 2 weeks prior to the time of enrollment. Electrolyte and hormonal supplementation may be used to treat these AEs provided the subject is stable on these supplements.
• Minimum of 2 weeks since the last dose of other hormone therapy and 3 weeks since the last dose of other systemic cancer therapy or radiotherapy (\> 4 weeks in case of nitrosoureas or radio-immuno conjugate therapy). Adjuvant hormonal therapy (e.g., tamoxifen) is allowed provided the original tumor diagnosis was more than 3 years before the first dose of study medication. Subjects with prostate cancer on stable doses of anti-hormone treatment may remain on therapy for this trial.
• Subjects must have adequate organ function.

You may not qualify if:

• Subject previously had a severe hypersensitivity reaction to treatment with another monoclonal antibody (mAb).
• Life expectancy \< 12 weeks.
• Subject has an Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) \> 2.
• Prior organ or stem cell transplant.
• Subjects with symptomatic ascites or pleural effusion. Subjects who are clinically stable for at least 2 weeks following treatment for these conditions (including therapeutic thoraco- or paracentesis) are eligible.
• Subject has a known active central nervous system (CNS) primary tumor or metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are clinically stable for at least 4 weeks prior to study entry, have no radiological evidence of new or enlarging brain metastases, and are off steroids or on a stable dose up to an equivalent of prednisone 10 mg/day for at least 15 days prior to first dose of study medication. Subjects who have symptoms consistent with CNS metastasis must have a negative magnetic resonance imaging (MRI) scan during the screening period.
• Subject has a known history of a hematologic malignancy, malignant primary brain tumor, or another malignant primary solid tumor (other than that under study), unless the subject has undergone potentially curative therapy with no evidence of recurrent disease for at least 3 years before the start of treatment.
• Subjects with a known history of AJCC Stage 1 cancer that has undergone potentially curative therapy with no evidence of recurrent disease for at least 1 year before the start of treatment may be eligible at the Investigator's discretion after consultation with the Sponsor.
• Subjects who underwent successful definitive resection of basal cell carcinoma of the skin, superficial bladder cancer, squamous cell carcinoma of the skin, in situ cervical cancer, or other in situ cancers at any time before the start of treatment, and have no evidence of recurrent disease, are eligible.
• Recent or ongoing serious infection including the following:
• Any uncontrolled Grade 3 or higher (per NCI-CTCAE version 5.0) viral, bacterial, or fungal infection within 2 weeks prior to the first dose of OR502. Routine antimicrobial prophylaxis is allowed.
• Uncontrolled infection with human immunodeficiency virus (HIV). Subjects on stable highly active antiretroviral therapy (HAART) with undetectable viral load and normal CD4 counts for at least 6 months prior to study entry are eligible. Serological testing for HIV at screening is not required.
• Known to be positive for hepatitis B virus (HBV) surface antigen, or any other positive test for hepatitis B indicating acute or chronic infection. Subjects who are or have received anti-HBV therapy and have undetectable HBV DNA for at least 6 months prior to study entry are eligible. Serological testing for hepatitis B at screening is not required.
• Known active hepatitis C as determined by positive serology and confirmed by polymerase chain reaction (PCR). Subjects on or having received anti-retroviral therapy are eligible provided they are virus-free by PCR for at least 6 months prior to study entry. Serological testing for hepatitis C at screening is not required.
• Known active or latent tuberculosis (testing at screening is not required).

Sponsors & Collaborators

• OncoResponse, Inc.: lead

Study Sites (4)

NEXT Austin

Austin, Texas, 78758, United States

RECRUITING

NEXT Dallas

Irving, Texas, 75039, United States

RECRUITING

NEXT Oncology

San Antonio, Texas, 78229, United States

RECRUITING

NEXT Virginia

Fairfax, Virginia, 22031, United States

RECRUITING

MeSH Terms

Conditions

Neoplasms; Neoplasm Metastasis; Melanoma; Carcinoma, Non-Small-Cell Lung

Interventions

cemiplimab

Condition Hierarchy (Ancestors)

Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases

Central Study Contacts

Lesley Skingley

CONTACT

905 407 6789; v-lskingley@oncoresponse.com

Study Design

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

Study Record Dates

• First Submitted: September 29, 2023
• First Posted: October 19, 2023
• Study Start: October 24, 2023
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): February 1, 2027
• Last Updated: January 7, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)