A Study of OR2805, a Monoclonal Antibody Targeting CD163, Alone and in Combination With Anticancer Agents
A Phase 1-2 Study of OR2805, a Monoclonal Antibody Targeting CD163, Alone and in Combination With Anticancer Agents in Subjects With Advanced Malignancies
1 other identifier
interventional
172
1 country
3
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 OR2805 administered as a monotherapy and in combination with anti-cancer agents in subjects with advanced solid tumors.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1 cancer
Started Sep 2021
3 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
September 9, 2021
CompletedFirst Submitted
Initial submission to the registry
September 27, 2021
CompletedFirst Posted
Study publicly available on registry
October 26, 2021
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 15, 2024
CompletedStudy Completion
Last participant's last visit for all outcomes
August 15, 2024
CompletedNovember 2, 2023
October 1, 2023
2.6 years
September 27, 2021
October 31, 2023
Conditions
Outcome Measures
Primary Outcomes (3)
Dose-limiting Toxicity
The incidence of DLTs during the DLT assessment period.
First 21 days of treatment.
Safety and Tolerability
The nature, frequency, and severity of adverse events and serious adverse events, treatment discontinuations due to toxicity, and clinical laboratory abnormalities; recording of infusion-related reactions; physical examination and ECG findings; vital sign measurements; ECOG performance status scores; markers of inflammation and immunogenicity.
Screening to 90 days from last dose.
Recommended Dose and Regimen (mono and combination therapy)
Determination of the MTD or maximum achievable dose, and the RP2D.
Screening to 90 days from last dose.
Secondary Outcomes (5)
Pharmacokinetics of OR2805
Day 1 of dosing through 21 days post last dose.
Pharmacokinetics of OR2805
Day 1 of dosing through 21 days post last dose.
Objective Response Rate (ORR)
Day 1 of dosing through every 90 after the last dose.
Disease Control Rate (DCR)
Day 1 of dosing through every 90 after the last dose.
Progression Free Survival (PFS)
Day 1 of dosing through every 90 after the last dose.
Study Arms (3)
OR2805 monotherapy and combination therapy dose-escalation phase (Part A)
EXPERIMENTALEscalating repeated doses of OR2805 by IV administration as monotherapy or in combination with cemiplimab or docetaxel in subjects with advanced solid tumors. OR2805 will be administered once every 3 weeks (Q3W) or once-weekly (QW) for 3 weeks as an IV infusion over 30 minutes. Cemiplimab will be administered as an IV infusion at a dose of 350 mg. Docetaxel will be administered as an IV infusion at a dose of 75 mg/m2.
OR2805 monotherapy and combination therapy dose-expansion phase (Part B)
EXPERIMENTALOR2805 administered IV at the RP2D and dosing regimen identified in Part A as monotherapy or in combination with cemiplimab or docetaxel in subjects with NSCLC and melanoma. Cemiplimab will be administered as an IV infusion at a dose of 350 mg. Docetaxel will be administered as an IV infusion at a dose of 75 mg/m2.
OR2805 biological effects phase (Part C)
EXPERIMENTALOR2805 administered IV at the RP2D and dosing regimen identified in Part A as monotherapy to determine the mechanism of action and potential predictors of response and pharmacodynamic markers in subjects with liposarcoma, leiomyosarcoma, or SCCHN or are not otherwise eligible for Cohort B.
Interventions
IgG1 monoclonal antibody that binds specifically to the CD163 protein.
IgG4 mAb that binds to PD-1 and blocks its interaction with PD-L1 and PD-L2.
An antineoplastic agent that acts by disrupting the microtubular network in cells that is essential for mitotic and interphase cellular functions.
Eligibility Criteria
You may qualify if:
- Informed consent signed by the subject prior to conducting study-specific procedures.
- Male or female subjects ≥ 18 and ≤ 100 years of age.
- Histological diagnosis as follows:
- Part A (dose-escalation Cohorts A1-A3): histological diagnosis of any type of carcinoma, sarcoma, or melanoma with progressive metastatic disease, or progressive locally advanced disease not amenable to local therapy.
- Part B (expansion Cohorts B1-B3): histological diagnosis of the relevant tumor type (NSCLC or melanoma) with advanced/metastatic disease not amenable to local therapy.
- a. Part C (biology cohort): histological or cytological diagnosis of any type of carcinoma, sarcoma, or melanoma with progressive metastatic disease, or progressive locally advanced disease not amenable to local therapy. At least 10 subjects each must have a diagnosis of SCCHN, dedifferentiated liposarcoma, or leiomyosarcoma with prior treatment described below.
- Prior therapies:
- a. Part A (dose-escalation) i. Subjects must have experienced 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. Part B (dose-expansion) i. Part B1 subjects (NSCLC) must have received platinum-based therapy, unless contraindicated, and a PD-1 or PD-L1 inhibitor. Subjects eligible for targeted therapies to EGFR, ALK, ROS, RET or NTRK (e.g., crizotinib) must have previously received and exhausted such therapies. Prior therapies may have been administered alone or in combination. Subjects must have received prior PD-(L)1-based therapy as the most recent prior therapy and demonstrated progression while on that therapy.
- ii. Part B2 subjects (NSCLC) must have received platinum-based therapy and a PD-1 or PD-L1 inhibitor unless contraindicated. Subjects eligible targeted therapies to EGFR, ALK, ROS, RET or NTRK (e.g., crizotinib) must have exhausted such therapies. Prior therapies may have been administered alone or in combination. Part B2 subjects may have received a total of 3 lines of prior therapy and are not required to have received a PD-(L)1-based therapy as the most recent therapy.
- iii. For melanoma: subjects must have received a PD-1 inhibitor, alone or in combination with another immunotherapy. Eligible subjects may have received BRAF- and MEK-targeted therapies. Subjects must have received prior PD-1-based therapy as the most recent therapy and demonstrated radiographic progression while on that therapy.
- c. Part C (biology cohort): subjects other than those with liposarcoma, leiomyosarcoma, or SCCHN must have experienced PD on an established standard medical 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 and must have no available demonstrated curative or life-prolonging therapies. Subjects with liposarcoma must have dedifferentiated liposarcoma, have received at least 1 prior systemic therapy, and require additional treatment. For leiomyosarcoma, subjects must have received at least 1 prior therapy for advanced or metastatic disease. For SCCHN, subjects must have received 1 prior line of chemotherapy and a PD-1- or PD-L1-targeted agent alone or in combination with chemotherapy unless contraindicated. No more than 2 chemotherapy regimens in the advanced setting for SCCHN are allowed. All subjects must have demonstrated progression on the most recent line of therapy.
- Subjects must have measurable disease per RECIST v1.1. Subjects in Part C must have at least one 1 lesion amenable to biopsy and that is not to be used for response assessment per RECIST v1.1.
- If not postmenopausal or surgically sterile, subjects must be willing to practice at least one of the following highly effective methods of birth control for at least a menstrual cycle (or partner's menstrual cycle, for male subjects) before and for 3 months after study medication administration: (1) true abstinence, when this is in line with the preferred and usual lifestyle of the subject, from sexual intercourse with a member of the opposite sex; (2) sexual intercourse with vasectomized male/sterilized female partner; (3) hormonal female contraceptive (oral, parenteral, intravaginal, implantable, or transdermal) for at least 3 consecutive months prior to investigational product administration (when not clinically contraindicated as in breast, ovarian, and endometrial cancers); (4) use of an intrauterine contraceptive device or intrauterine hormone-releasing system.
- Resolution of prior-therapy-related AEs (excluding alopecia and grade ≤ 2 peripheral neuropathy) to ≤ grade 1 per CTCAE v5.0, 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.
- +4 more criteria
You may not qualify if:
- Subject previously had a severe hypersensitivity reaction to treatment with another mAb.
- Subject has ECOG PS \> 2.
- Life expectancy \<12 weeks.
- Prior organ or stem cell transplant.
- Subjects with symptomatic ascites or pleural effusion.
- Subject has a known active 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 MRI during in 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 that disease for at least 3 years.
- Recent or ongoing serious infection including the following:
- Any uncontrolled grade 3 or higher (per CTCAE v5.0) viral, bacterial, or fungal infection within 2 weeks prior to the first dose of OR2805. Routine antimicrobial prophylaxis is allowed.
- Uncontrolled infection with HIV. Subjects on stable HARRT therapy 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 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.
- Known active hepatitis C as determined by positive serology and confirmed by PCR. Subjects on or having received antiretroviral therapy are eligible provided they are virus-free by PCR for at least 6 months prior to study entry.
- Known active or latent tuberculosis (testing at screening is not required).
- Use of systemic corticosteroids within 15 days or other immunosuppressive drugs within 30 days prior to start of the study, with the exception of corticosteroids as replacement therapy up to an equivalent of prednisone 10 mg/day which are allowed. Pretreatment with dexamethasone is allowed for subjects receiving OR2805 in combination with docetaxel. Inhaled, topical, or intraarticular steroids are allowed.
- Subject has received an investigational product or been treated with an investigational device within 30 days prior to first administration of study medication.
- +9 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (3)
HonorHealth Research Institute
Scottsdale, Arizona, 85258, United States
NEXT Austin
Austin, Texas, 78758, United States
NEXT Oncology
San Antonio, Texas, 78229, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Central Study Contacts
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 27, 2021
First Posted
October 26, 2021
Study Start
September 9, 2021
Primary Completion
April 15, 2024
Study Completion
August 15, 2024
Last Updated
November 2, 2023
Record last verified: 2023-10
Data Sharing
- IPD Sharing
- Will not share