CRD3874-SI for Sarcoma

Recruiting at 6 trial locations

Overseen By Sandra D'Angelo

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: Immunosuppressants, Steroids, Antibiotics, others

Disqualifiers: Autoimmune disease, Organ transplant, CNS metastases, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 28

Duration: 48 weeks

72 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new study drug called CRD3874-SI to assess its safety and potential side effects. Researchers aim to determine the highest safe dose for treating advanced or spreading solid tumors, such as sarcoma and Merkel Cell Carcinoma. Individuals with cancers unresponsive to other treatments or unable to undergo standard therapies might be suitable candidates for this trial. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new drug.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on immunosuppressive therapy or certain other treatments, you may need to adjust or stop them. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that CRD3874-SI is likely to be safe for humans?

Research has shown that CRD3874-SI has a good safety record in early studies. In tests with animals, such as monkeys, the drug was well-tolerated, with no serious side effects. A study with humans also found CRD3874-SI to be safe, suggesting it might be safe for people as well.

The drug targets a protein called STING, which aids the immune system in fighting cancer cells. Early results in humans are promising, demonstrating both safety and potential benefits. However, as this is an early study, further research is needed to confirm these findings. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for sarcoma, which often involve chemotherapy and radiation, CRD3874-SI introduces a unique approach by using an innovative delivery method of weekly infusions. This treatment is particularly exciting because it offers a new dosing schedule that adjusts based on patient tolerance, potentially allowing for continuous weekly treatment if well-tolerated. Researchers are hopeful that this flexibility could lead to better patient outcomes by maintaining consistent drug exposure and possibly reducing side effects associated with more aggressive treatment regimens.

What evidence suggests that CRD3874-SI might be an effective treatment for sarcoma?

Research has shown that CRD3874-SI, the investigational treatment in this trial, could be promising because it helps the immune system better identify and combat cancer cells. Early results suggest that CRD3874-SI might effectively boost the body's defense against tumors such as sarcoma. Although detailed information from human studies remains limited, early research indicates that the treatment appears safe and effective. Further studies are needed to confirm these initial findings. ^{1 2 3 6 7}

Who Is on the Research Team?

Ciara Kelly, MBBCh BAO

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with advanced or metastatic sarcoma, Merkel cell carcinoma, or neuroendocrine carcinoma that's worsened after treatment. They must be in good health otherwise, have a life expectancy of at least three months, and not be pregnant. Participants need to agree to biopsies and have measurable disease. Those with certain heart conditions, active infections, other cancers, severe allergies to study drug components or recent treatments are excluded.

Inclusion Criteria

I weigh ≤90kg for dose level 5 or ≤70kg for dose level 6.

I am willing to follow the trial's rules and undergo tumor biopsies if needed.

Women who could become pregnant must have a negative pregnancy test before starting the study.

Exclusion Criteria

You have had a very bad allergic reaction to the study drug or any of its ingredients.

Patients expecting to conceive or father children within the projected duration of the trial

My heart condition has been stable for the last 6 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive CRD3874-SI with dose escalation to determine the maximum tolerated dose, followed by dose expansion to assess safety and efficacy

48 weeks

Weekly infusions during 28-day cycles

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• CRD3874-SI

Trial Overview CRD3874-SI is being tested in this study. Researchers will first find the highest dose with acceptable side effects before testing its effectiveness against specific cancers like Sarcoma and Merkel Cell Cancer. The trial involves gradually increasing doses for early participants then using the safest high dose on later groups.

How Is the Trial Designed?

Group I: CRD3874-SI Experimental Treatment 1 Intervention

Phase 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 onwards if a patient is tolerating treatment well and agreeable to continue continuous weekly treatment this will be permitted.

CRD3874-SI is already approved in United States for the following indications:

Approved in United States as CRD3874-SI for:

• Advanced solid tumors
• Sarcoma
• Merkel Cell Carcinoma

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Curadev Pharma

Collaborator

Trials

1

Recruited

70+

Published Research Related to This Trial

Sarcomas, which are diverse tumors of mesenchymal origin, have low response rates to traditional chemotherapy, highlighting the need for targeted therapies based on specific molecular mechanisms.

Recent advancements have identified several novel druggable targets in various sarcoma subtypes, such as MDM2 amplifications in liposarcomas and the mTOR pathway in malignant peripheral nerve sheath tumors, paving the way for more effective, targeted clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel pathways and molecular targets for the treatment of sarcoma. Frith, AE., Hirbe, AC., Van Tine, BA.[2021]

KIT is a key driver in gastrointestinal stromal tumors (GIST), and targeting it with imatinib has led to increased interest in finding other therapeutic targets for various sarcoma subtypes.

Current clinical trials often include unselected patient populations, which can dilute the effectiveness of targeted therapies; however, emerging data suggest that specific targeted treatments may be more effective when tailored to particular histologic subtypes of sarcomas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeted therapy in sarcoma: should we be lumpers or splitters? Riedel, RF., Maki, RG., Wagner, AJ.[2020]

Recent international conferences highlighted the complexity of sarcoma genetics, revealing that fusion oncogenes play a significant role in the behavior of sarcomas, particularly in pediatric cases, which could lead to more targeted therapies.

Molecular characterization of sarcomas is paving the way for subtype-specific treatments, with promising developments in targeted therapies for certain sarcoma types based on actionable mutations, although challenges remain for others like clear cell sarcoma and osteosarcoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel Aspects of Genetics, Molecular Biology and Clinical Oncology of Sarcomas. Houfková, K., Hatina, J.[2020]

Recent advancements in understanding the specific biology of different sarcoma subtypes have led to the development of targeted therapies that focus on unique molecular alterations, which are currently being tested in clinical trials.

While some sarcomas respond to existing immunotherapies like PD-1 inhibitors, there is a need for novel treatments, including new immune checkpoint targets and cellular therapies, to improve outcomes for most sarcoma patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Emerging Targeted and Immune-Based Therapies in Sarcoma. Pollack, SM., Ingham, M., Spraker, MB., et al.[2019]

In a study of 230 sarcoma tumors, PD-L1 immunoreactivity was observed, with a notable subset showing over 50% positivity, suggesting potential for immune checkpoint inhibitor therapy in these patients.

Despite the presence of PD-L1 in some tumors, there was no significant correlation between PD-L1 levels and patient survival outcomes, indicating that more research is needed to establish effective treatment strategies for sarcomas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of PD-L1 Expression in Undifferentiated Pleomorphic Sarcomas, Liposarcomas and Chondrosarcomas. Zhang, Y., Chen, Y., Papakonstantinou, A., et al.[2022]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.TPS2690

Phase I trial of CRD3874-SI, a systemically administered ... The dose escalation phase will explore the safety and tolerability of CRD3874-SI across 6 dose levels following a standard 3+3 design. Dose ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06021626

A Study of CRD3874-SI in People With Solid Tumors 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 ...

3. jitc.bmj.com jitc.bmj.com/content/12/Suppl_1/A11.1

P01.09 CRD3874-SI: a novel allosteric STING agonist with ... This profile of retaining the high efficacy of a STING agonist while demonstrating systemic safety is unique to CRD3874-SI.

4. withpower.com withpower.com/trial/phase-1-carcinoma-merkel-cell-7-2023-b349d

CRD3874-SI for Sarcoma · Recruiting Participants for Phase ... 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 ...

5. researchgate.net researchgate.net/publication/382046494_Phase_I_trial_of_CRD3874-SI_a_systemically_administered_STING_agonist_in_patients_with_advanced_solid_tumors

Phase I trial of CRD3874-SI, a systemically administered STING ... Both clinical and pre-clinical data were reviewed primarily from randomized controlled trials, observational studies, peer-reviewed articles, meta-analyses and ...

6. mskcc.org mskcc.org/cancer-care/clinical-trials/23-169

A Phase 1 Study of CRD3874-SI in People With Advanced ... CRD3874-SI attaches to a type of protein called a STING. This protein encourages immune cells to kill cancer cells, which may slow or stop cancer growth.

7. clin.larvol.com clin.larvol.com/trial-detail/NCT06021626

A Study of CRD3874-SI in People With Solid Tumors CRD3874-SI has demonstrated an encouraging safety and efficacy profile in a first-in-human study at MSK." ASCO 2024 (On-demand, Poster) - TPS2690 - Phase I ...