A Study of CRD3874-SI in People With Solid Tumors
A Phase I Trial of CRD3874-SI, a STING Agonist, in Patients With Advanced/Metastatic Malignant Solid Tumors
1 other identifier
interventional
81
1 country
7
Brief Summary
This study will test the safety of a study drug called CRD3874-SI. The researchers will test different doses of CRD3874-SI to find the highest dose that causes few or mild side effects in participants. After the researchers find the highest safe dose of CRD3874-SI, they will test that dose in new groups of participants to help them learn more about the side effects of the study drug and find out whether CRD3874-SI is an effective treatment for for patients with advanced or metastatic malignant solid tumors including sarcoma and Merkel Cell Carcinoma. (MCC), Head and neck squamous cell carcinoma (HNSCC), Adenoid cycstic carcinoma (ACC), Uveal Melanoma, Muscosal and Acral melanoma, and Non small cell lung cancer. The researchers will also look at how the body absorbs, distributes, and gets rid of CRD3874-SI, and the how the body and immune system respond to CRD3874-SI.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Aug 2023
Longer than P75 for phase_1
7 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
August 25, 2023
CompletedFirst Submitted
Initial submission to the registry
August 28, 2023
CompletedFirst Posted
Study publicly available on registry
September 1, 2023
CompletedPrimary Completion
Last participant's last visit for primary outcome
August 1, 2029
ExpectedStudy Completion
Last participant's last visit for all outcomes
August 1, 2029
April 29, 2026
April 1, 2026
5.9 years
August 28, 2023
April 24, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
maximum tolerated dose (MTD)
The MTD is defined as the highest dose level studied at which \<2 subjects out of 6 experience a DLT. A dose level under consideration as the MTD will be expanded to six patients if only three have been accrued.
1 year
objective response rate (ORR) (Dose expansion)
by RECIST v1.1
up to 48 weeks
Study Arms (1)
CRD3874-SI
EXPERIMENTALPhase 1a: starting dose of 0.1 mg/kg, Phase 1b: RP2D determined during Phase 1a. Cycle 1 \& 2: once weekly infusion x 4 (Days 1, 8, 15, 22) over 28-day cycle. Cycle 3 onwards: weekly infusion x 3 (Days 1, 8, 15) over 28-day cycle From cycle 3 on wards if a patient is tolerating treatment well and agreeable to continue continuous weekly treatment this will be permitted. The dose expansion phase will explore CRD3874-SI at the RP2D and one additional clinically active dose levels in select solid tumor type. In the dose expansion phase, research blood tests for Peripheral blood mononuclear cells (PBMCs) will be performed before study drug administration on Day 1 of Cycles 1, 2 and 3 and the EOT visit (± 3 days).
Interventions
Starting dose is 0.1 mg/kg for weekly IV infusion of CRD3874-SI. Cohort CRD3874-SI Dose level (mg/kg) 1. 0.1 2. 0.3 3. 0.9 4. 1.8 5. 2.7 6. 4.05
Eligibility Criteria
You may qualify if:
- Male or female age ≥ 18 years at the time of informed consent.
- Be capable, willing, and able to provide written informed consent.
- Be willing to comply with clinical trial instructions and requirements, including tumor biopsies (if feasible and required per protocol).
- Patients must have a locally advanced or metastatic cancer, a malignant solid tumor that has progressed on at least one line of systemic therapy or for which no standard treatment is available, the participant is intolerant to available treatment, or the participant declined standard of care systemic therapy.
- In the dose escalation phase study patients with the following tumor types will be eligible: Of note patients who declined or were intolerable of standard of care systemic therapy will be considered in all dose expansion cohorts.
- Head and neck squamous cell carcinoma (HNSCC)
- Participants must have histologically or cytologically confirmed recurrent and/or metastatic HNSCC and must have received 1-2 prior lines of systemic anti-cancer therapy including a checkpoint inhibitor (patients treated initially with immune checkpoint blockade alone followed by the addition of other drugs in combination \[i.e., cytotoxic chemotherapy or EGFR inhibitor\], will be considered 1 line of therapy.
- HPV positive (p16 IHC positive or HPV RNA ISH positive), PD-L1 CPS score high (≥1)
- HPV negative (p16 IHC negative or HPV RNA ISH negative), PD-L1 CPS score high (≥1)
- Adenoid cystic carcinoma (ACC)
- Participants must have histologically or cytologically confirmed recurrent and/or metastatic ACC (cancers arising from non-salivery gland primary sites are eligible) and may have received none or up 2 prior lines of systemic anti-cancer therapy.
- Merkel cell carcinoma (MCC)
- Participants must have histologically or cytologically confirmed recurrent and or metastatic MCC and must have received at least one but no more than 3 prior lines of systemic anti-cancer therapy including a checkpoint inhibitor and may not have received prior chemotherapy for MCC.
- Monotherapy alone
- Radiation therapy
- +28 more criteria
You may not qualify if:
- Known prior severe hypersensitivity to an investigational product or any component of the study drug therapy's formulations including polyethylene glycol (PEG), (NCI CTCAE v5.0 Grade ≥ 3)
- Evidence of clinically significant immunosuppression such as the following:
- Primary immunodeficiency state such as Severe Combined Immunodeficiency Disease
- Concurrent opportunistic infection
- Receiving systemic immunosuppressive therapy (\> 2 weeks) including oral steroid doses \> 10 mg/day of prednisone or equivalent within 7 days prior to enrollment. In the setting of non-immune mediated indications for use, chronic/active low dose steroid (equivalent to \</=10mg/day prednisone) use may be permitted at the discretion of the principal investigator.
- Current use of immunosuppressive medication, EXCEPT for the following:
- I. Intranasal, inhaled, ocular, topical steroids, or local steroid injection (e.g., intraarticular injection) II. Systemic corticosteroids at physiologic doses ≤ 10 mg/day of prednisone or equivalent III. Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication)
- Prior organ transplantation, including allogenic stem-cell transplantation. Consideration will be given to allow patients with a history of autologous transplantation enroll if they are at least 5 years beyond the completion of the transplant pending discussion with the principal investigator.
- History or evidence of symptomatic autoimmune disease (e.g., pneumonitis, glomerulonephritis, vasculitis, or other), or history of active autoimmune disease that has required systemic treatment (i.e., use of corticosteroids, immunosuppressive drugs or biological agents used for treatment of autoimmune diseases) in past 2 years prior to enrollment. Replacement therapy (e.g., thyroxine for hypothyroidism, insulin for diabetes or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment for autoimmune disease.
- Systemic antibiotics received ≥ 7 days prior to the first dose of study drugs.
- Uncontrolled medical condition including current active infection requiring systemic therapy or symptomatic congestive heart failure within 6 months that in the investigators opinion compromise the ability of the patient to complete all study related requirements safely
- Inability to comply with protocol required procedures
- Resting QTc interval by Friderica's formula ≥ 470 ms on a 12-lead electrocardiogram (ECG) for males and females
- Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment or 5 half-lives, if shorter.
- Has had prior chemotherapy or targeted small molecule therapy within 3 weeks, anti-cancer monoclonal antibody (mAb) within 4 weeks or OR 5 half-lives, if shorter, or radiation therapy within 2 weeks prior to the first CRD3874 infusion prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent
- +25 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Memorial Sloan Kettering Cancer Centerlead
- Curadev Pharmacollaborator
Study Sites (7)
Memorial Sloan Kettering at Basking Ridge (Limited Protocol Activities)
Basking Ridge, New Jersey, 07920, United States
Memorial Sloan Kettering Monmouth (Limited Protocol Activities)
Middletown, New Jersey, 07748, United States
Memorial Sloan Kettering Bergen (Limited Protocol Activities)
Montvale, New Jersey, 07645, United States
Memorial Sloan Kettering Suffolk - Commack (Limited Protocol Activities)
Commack, New York, 11725, United States
Memorial Sloan Kettering Westchester (Limited Protocol Activities)
Harrison, New York, 10604, United States
Memorial Sloan Kettering Cancer Center (All Protocol Activities)
New York, New York, 10065, United States
Memorial Sloan Kettering Nassau (Limited Protocol Activities)
Rockville Centre, New York, 11553, United States
Related Links
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Ciara Kelly, MBBCH BAO
Memorial Sloan Kettering Cancer Center
Central Study Contacts
Ciara Kelly, MBBChBAO
CONTACT
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
August 28, 2023
First Posted
September 1, 2023
Study Start
August 25, 2023
Primary Completion (Estimated)
August 1, 2029
Study Completion (Estimated)
August 1, 2029
Last Updated
April 29, 2026
Record last verified: 2026-04
Data Sharing
- IPD Sharing
- Will share
Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.