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

Trial Summary

What is the purpose of this trial?

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.

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.

What makes the drug CRD3874-SI unique for treating sarcoma?

CRD3874-SI is unique because it may target specific molecular pathways or genetic mutations in sarcoma subtypes, which are not effectively addressed by standard cytotoxic chemotherapy. This approach aligns with the growing trend of developing targeted therapies based on the molecular characteristics of different sarcoma subtypes. ^{1 2 3 4 5}

Research Team

Ciara Kelly, MBBCh BAO

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Novel pathways and molecular targets for the treatment of sarcoma. [2021]

2. Czech Republic pubmed.ncbi.nlm.nih.gov

Novel Aspects of Genetics, Molecular Biology and Clinical Oncology of Sarcomas. [2020]

3. United States pubmed.ncbi.nlm.nih.gov

Emerging Targeted and Immune-Based Therapies in Sarcoma. [2019]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Evaluation of PD-L1 Expression in Undifferentiated Pleomorphic Sarcomas, Liposarcomas and Chondrosarcomas. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Targeted therapy in sarcoma: should we be lumpers or splitters? [2020]