DCC-3014 + Avelumab for Sarcoma

Overseen By William Tap, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: Immunosuppressants, Steroids

Disqualifiers: Cardiovascular disease, CNS metastases, Autoimmune disease, HIV, Hepatitis, others

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine the safest dose of a new drug, DCC-3014, when combined with avelumab (also known as Bavencio, an immunotherapy drug) for treating advanced or metastatic sarcomas, which are aggressive cancers. Researchers seek to ensure the combination does not cause serious side effects. The trial is recruiting individuals diagnosed with high-grade sarcomas who have already tried at least one treatment, such as chemotherapy, without success. Participants should have a form of sarcoma that is advanced or spreading and must be willing to undergo mandatory biopsies. 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 therapy.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify whether you need to stop taking your current medications. However, if you are using immunosuppressive medications or have recently received certain treatments like chemotherapy or monoclonal antibodies, you may need to stop or adjust them before joining the trial. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that the combination of DCC-3014 and avelumab is generally safe and well-tolerated by patients. Studies have found that these two drugs together usually do not cause serious side effects for most people. This combination has been tested in patients with advanced sarcomas, a type of cancer.

Specifically, the studies found that this treatment can lower certain immune cells in the body that might help the cancer grow. This finding is promising for fighting cancer while being safe for patients. Avelumab, one of the drugs in the combination, already has FDA approval for other uses, which increases confidence in its safety.

Overall, the data so far suggest that people can handle this treatment without major problems. However, as with any treatment, individual experiences may vary, and side effects could occur. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about DCC-3014 and Avelumab for sarcoma because these treatments offer new ways to tackle the disease. Unlike the standard chemotherapy and radiation therapies, DCC-3014 works by inhibiting a specific protein called CSF1R, which helps regulate immune cells in the tumor environment, potentially making the cancer more vulnerable to attack. Meanwhile, Avelumab is an immunotherapy that blocks a protein called PD-L1, helping the immune system recognize and destroy cancer cells more effectively. This combination could provide a more targeted approach to treating high-grade sarcomas, potentially leading to better outcomes for patients.

What evidence suggests that DCC-3014 + Avelumab might be an effective treatment for sarcoma?

Research has shown that avelumab, a medicine that aids the immune system, effectively treats various sarcomas, including undifferentiated pleomorphic sarcoma and leiomyosarcoma. Studies have found that avelumab helps the body's defenses identify and attack cancer cells. In this trial, participants will receive a combination of DCC-3014 and avelumab. DCC-3014 is a newer medicine targeting a specific aspect of cancer cell growth. Early research suggests that combining DCC-3014 with avelumab might reduce certain immune cells that assist tumor growth. Although more research is needed, this combination appears promising for treating advanced sarcomas. ^{1 2 6 7 8}

Who Is on the Research Team?

Sandra D'Angelo, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

Adults (18+) with advanced or metastatic sarcomas, specifically undifferentiated pleomorphic, myxofibrosarcoma, leiomyosarcoma, or dedifferentiated liposarcoma. Participants must have had at least one prior systemic therapy and show measurable disease progression. They should be in good health otherwise and willing to use effective contraception.

Inclusion Criteria

Be capable, willing, and able to provide written informed consent/assent

Be willing to comply with clinical trial instructions and requirement, including mandatory biopsies

Dose expansion phase: Patients must have a histologically confirmed metastatic and/or locally undifferentiated pleomorphic sarcoma, myxofibrosarcoma, leiomyosarcoma, or dedifferentiated liposarcoma

Exclusion Criteria

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

Evidence or clinically significant interstitial lung disease or active, noninfectious pneumonitis related to prior immunotherapy treatment

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 day prior to trial treatment

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive escalating doses of DCC-3014 in combination with avelumab to determine the maximum tolerated dose

48 weeks

Dose Expansion

Participants receive the determined dose of DCC-3014 and avelumab to evaluate the overall response rate

48 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Avelumab
• DCC-3014

Trial Overview The trial is testing the combination of DCC-3014 with Avelumab to determine the safest dose for treating advanced sarcomas without causing severe side effects. The study involves participants who meet specific criteria related to their cancer type and previous treatments.

How Is the Trial Designed?

Group I: Advanced High-grade Sarcoma Experimental Treatment 2 Interventions

Dose Escalation: Up to 18 pts with locally advanced or metastatic high-grade sarcomas Dose Expansion: 10 pts per each diagnosis - undifferentiated pleomorphic sarcoma or myxofibrosarcoma, Leiomyosarcoma, Dedifferentiated liposarcoma

Avelumab is already approved in European Union, United States, Japan for the following indications:

Approved in European Union as Bavencio for:

• Merkel cell carcinoma
• Renal cell carcinoma
• Urothelial carcinoma

Approved in United States as Bavencio for:

• Merkel cell carcinoma
• Renal cell carcinoma
• Urothelial carcinoma

Approved in Japan as Bavencio for:

• Merkel cell carcinoma
• Renal cell carcinoma
• Urothelial carcinoma

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

ENABLE MEDICINE

Collaborator

Trials

1

Recruited

30+

Published Research Related to This Trial

Avelumab is an antibody that blocks programmed cell death ligand-1 (PD-L1) and has received accelerated approval in the USA for treating metastatic Merkel cell carcinoma (mMCC) in both adults and children aged 12 and older.

The drug is also undergoing regulatory reviews for other cancer treatments, including urothelial carcinoma, indicating its potential as a versatile cancer therapy in various stages of development worldwide.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Avelumab: First Global Approval. Kim, ES.[2022]

In the JAVELIN Lung 100 trial involving 1214 patients with advanced NSCLC, avelumab showed longer median progression-free survival (PFS) compared to platinum-based chemotherapy (8.4 months vs. 5.6 months), indicating its potential efficacy as a first-line treatment.

Although avelumab demonstrated longer median overall survival (OS) compared to chemotherapy (20.1 months vs. 14.9 months), the differences were not statistically significant, suggesting that while avelumab may be beneficial, it did not meet the primary objective of the trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Avelumab Versus Platinum-Based Doublet Chemotherapy as First-Line Treatment for Patients With High-Expression Programmed Death-Ligand 1-Positive Metastatic NSCLC: Primary Analysis From the Phase 3 JAVELIN Lung 100 Trial. Reck, M., Barlesi, F., Yang, JC., et al.[2023]

In a phase 2 study involving 85 patients with metastatic sarcoma, the combination of nivolumab and ipilimumab showed a higher confirmed response rate (16%) compared to nivolumab alone (5%), indicating that the combination therapy may be more effective for certain sarcoma subtypes.

While both treatments had manageable safety profiles, serious treatment-related adverse events occurred in 19% of patients receiving nivolumab and 26% in those receiving the combination therapy, suggesting that while the combination is promising, careful monitoring for side effects is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab with or without ipilimumab treatment for metastatic sarcoma (Alliance A091401): two open-label, non-comparative, randomised, phase 2 trials. D'Angelo, SP., Mahoney, MR., Van Tine, BA., et al.[2021]

In a phase 2 trial involving 62 patients with advanced or metastatic sarcoma, the combination of durvalumab and tremelimumab showed a promising progression-free survival rate of 49% at 12 weeks, indicating its potential efficacy as a treatment option.

While the treatment was generally active, it was associated with some serious adverse events, including one case of grade 5 pneumonitis and colitis, highlighting the need for careful monitoring of patients during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab plus tremelimumab in advanced or metastatic soft tissue and bone sarcomas: a single-centre phase 2 trial. Somaiah, N., Conley, AP., Parra, ER., et al.[2023]

In a phase 2 study involving 86 patients with advanced soft-tissue or bone sarcoma, pembrolizumab demonstrated some efficacy, particularly in undifferentiated pleomorphic sarcoma (40% response rate) and dedifferentiated liposarcoma (20% response rate), although the overall response rate did not meet the primary endpoint.

The treatment was associated with some serious adverse events, including immune-related conditions like adrenal insufficiency and pneumonitis, highlighting the need for careful monitoring during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab in advanced soft-tissue sarcoma and bone sarcoma (SARC028): a multicentre, two-cohort, single-arm, open-label, phase 2 trial. Tawbi, HA., Burgess, M., Bolejack, V., et al.[2022]

In a study of 84 patients with advanced sarcomas treated with off-label anti-PD1 immunotherapy, those with cutaneous primary tumors showed a significantly higher clinical benefit rate of 58%, compared to 11% for non-cutaneous tumors, indicating that tumor location is a key factor in treatment efficacy.

Patients with cutaneous sarcomas also experienced longer progression-free survival (8.6 months vs. 2.5 months) and overall survival (19.0 months vs. 9.2 months), suggesting that cutaneous primary site is a stronger predictor of response to immunotherapy than histological subtype.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-PD-1 therapy in advanced sarcomas: is cutaneous primary site a stronger predictor of response than histologic subtype? Miao, R., Swank, J., Melzer, D., et al.[2023]

In a phase II study of pembrolizumab for advanced sarcoma, a 17.5% response rate was observed, particularly in undifferentiated pleomorphic sarcoma and dedifferentiated liposarcoma, indicating its potential efficacy in these subtypes.

Higher densities of activated T cells and tumor-associated macrophages expressing PD-L1 in pre-treatment biopsies were associated with better responses to pembrolizumab, suggesting that specific immune features may predict treatment outcomes and progression-free survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Correlative Analyses of the SARC028 Trial Reveal an Association Between Sarcoma-Associated Immune Infiltrate and Response to Pembrolizumab. Keung, EZ., Burgess, M., Salazar, R., et al.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04242238

Study of DCC-3014 in Combination With Avelumab ... Adequate performance status: ECOG 0 or 1/KPS 100-70%; Patients must have at least one prior line of systemic therapy (e.g. chemotherapy, targeted or biological ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9249583/

A Phase 1/2 Trial Combining Avelumab and Trabectedin for ... This study aimed to evaluate the safety and efficacy of trabectedin with anti-PD-L1 antibody avelumab in patients with advanced LMS and LPS.

3. go.drugbank.com go.drugbank.com/drugs/DB11945/clinical_trials?conditions=DBCOND0044623%2CDBCOND0118909%2CDBCOND0016143%2CDBCOND0041813%2CDBCOND0165796&phase=1&purpose=treatment&status=completed

Avelumab Completed Phase 1 Trials for Undifferentiated ... Avelumab Completed Phase 1 Trials for Undifferentiated Pleomorphic Sarcoma (UPS) / Sarcomas / Dedifferentiated Liposarcoma / Myxofibrosarcoma / Leiomyosarcoma ( ...

4. withpower.com withpower.com/trial/phase-1-liposarcoma-2020-74a2c

DCC-3014 + Avelumab for Sarcoma · Info for Participants This trial is testing the safest dose of a new drug, DCC-3014, combined with an existing drug, avelumab, for patients with advanced or spreading sarcomas.

5. ichgcp.net ichgcp.net/clinical-trials-registry/NCT04242238

DCC-3014 and Avelumab in Sarcoma and Leiomyosarcoma and ... This study is being done to find the safest dose of DCC-3014 that can be given with avelumab to participants with advanced or metastatic sarcomas that will ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12511195/

Immunotherapy in the Treatment of Undifferentiated ... Undifferentiated pleomorphic sarcoma (UPS) and myxofibrosarcoma (MFS) are among the most common adult soft tissue sarcoma (STS) subtypes.

7. ascopubs.org ascopubs.org/doi/10.1200/EDBK_432234

Immunotherapy in Sarcoma: Current Data and Promising ... A phase I clinical trial investigated the small-molecule inhibitor DCC-3014 in conjunction with avelumab in patients with metastatic sarcoma ...

8. nature.com nature.com/articles/s41392-025-02278-9

Reshaping the tumor microenvironment of cold soft-tissue ... Safety and efficacy of regorafenib in patients with advanced soft tissue sarcoma (REGOSARC): a randomised, double-blind, placebo-controlled ...