A Study of CRD3874-SI in People With Solid Tumors

Recruiting now · Phase 1

Conditions studied: Sarcoma, Merkel Cell Carcinoma

In brief

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.

Key facts

Study ID

NCT06021626

Run by

Memorial Sloan Kettering Cancer Center

People needed

81

Starts

2023-08-25

Expected to finish

2029-08-01

Last updated by the study team

2026-06-05

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

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
• Patients will receive palliative radiation therapy to a tumor site if they have at least one other site of measureable disease that can be chosen as the target lesion to assess response to investigational therapy.
• Sarcoma that has demonstrated clinical benefit or an objective response to immune checkpoint blockade or sarcoma subtypes that are considered immunogenic subtypes including but not limited to undifferentiated pleomorphic (UPS) or myxofibrosarcoma (MFS), angiosarcoma, alveolara soft part sarcoma, or undifferentiated sarcoma will be considered.
• Melanoma
• Uveal Melanoma
• Participants must have histologically or cytologically confirmed recurrent and/or metastatic uveal melanoma and received at least one but no more than two prior lines of systemic anti-cancer therapy including tebentafusp (if HLA-A 02:01+, unless patient declined or was deemed ineligible) and/or immune checkpoint inhibitor. Melphalan PHP will count as a line of therapy if give on its own. Unlimited partial hepatic directed therapy will be permitted.
• Mucosal and Acral melanoma
• Participants must have histologically or cytologically confirmed recurrent and/or metastatic mucosal or acral melanoma and received at least one but no more than two prior lines of systemic anti-cancer therapy including prior exposure to immune checkpoint inhibition. Patients treated with BRAF-MEK therapy may have up to 3 prior lines of therapy.
• Non small cell lung cancer
• Participants must have histologically or cytologically confirmed locally advanced/metastatic non-small cell lung cancer with prior exposure to immune checkpoint inhibition and received at least one but no more than 2 prior lines of systemic anti-cancer therapy.
• Participants must have histologically or cytologically confirmed locally advanced/metastatic sarcoma and must have received at least one but no more than 2 prior lines of systemic anti-cancer therapy. Patients will receive palliative radiation therapy to a tumor site if they have at least one other site of measureable disease that can be chosen as the target lesion to assess response to investigational therapy

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
• Note: Alopecia or other Grade ≤ 2 not constituting a safety risk based on investigator's judgment are acceptable
• Note: If patient received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study therapy
• Evidence of clinically significant interstitial lung disease, history of interstitial lung disease, or active, noninfectious pneumonitis related to prior immunotherapy treatment.
• History of unstable or deteriorating cardiovascular disease within the previous 6 months prior to screening including but not limited to the following:
• Unstable angina or myocardial infarction
• CVA/stroke
• Congestive heart failure (New York Heart Association [NYHA] Class III or IV
• Uncontrolled clinically significant arrhythmias.
• Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
• Patients with previously treated brain metastases or carcinomatous meningitis may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment.

Where it is running

• Memorial Sloan Kettering at Basking Ridge (Limited Protocol Activities) — Basking Ridge, New Jersey, United States (enrolling)
• Memorial Sloan Kettering Monmouth (Limited Protocol Activities) — Middletown, New Jersey, United States (enrolling)
• Memorial Sloan Kettering Bergen (Limited Protocol Activities) — Montvale, New Jersey, United States (enrolling)
• Memorial Sloan Kettering Suffolk - Commack (Limited Protocol Activities) — Commack, New York, United States (enrolling)
• Memorial Sloan Kettering Westchester (Limited Protocol Activities) — Harrison, New York, United States (enrolling)
• Memorial Sloan Kettering Cancer Center (All Protocol Activities) — New York, New York, United States (enrolling)
• Memorial Sloan Kettering Nassau (Limited Protocol Activities) — Rockville Centre, New York, United States (enrolling)

Full record on ClinicalTrials.gov

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