Oleclumab + Durvalumab for Advanced Sarcoma

(DOSa Trial)

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Immunosuppressants, Anti-PD1, Anti-PD-L1, Anti-CD73

Disqualifiers: Autoimmune disease, CNS metastases, HIV, others

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

Prior Safety Data This treatment has passed at least one previous human trial

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

Compensation: Varies

Number of Visits: 5

Duration: Up to 4 months

75 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing two immunotherapy drugs, oleclumab and durvalumab, in patients with difficult-to-treat sarcoma. These drugs help the immune system to find and destroy cancer cells and may stop the cancer from growing and spreading.

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

The trial does not specify if you need to stop taking your current medications. However, you cannot be on any other cancer treatments while participating, and you should not use immunosuppressive medications within 14 days before starting the trial. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug Durvalumab (Imfinzi) for treating advanced sarcoma?

Durvalumab, a drug that helps the immune system fight cancer, has shown effectiveness in treating various cancers like bladder and lung cancer. While specific data for sarcoma is limited, its use in other cancers suggests potential benefits. ^{1 2 3 4 5}

What makes the drug combination of Oleclumab and Durvalumab unique for treating advanced sarcoma?

This treatment is unique because it combines two drugs that target different immune pathways: Durvalumab blocks PD-L1 to enhance the immune system's attack on cancer cells, while Oleclumab targets CD73 to reduce local immunosuppression in tumors. This dual approach aims to improve the immune response against advanced sarcoma, a condition with few standard treatment options. ^{1 2 3 4 6}

Research Team

Neeta Somaiah, MD

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

Adults and children over 12 with recurrent, refractory, or metastatic sarcoma who have tried standard treatments without success. They must be in good health otherwise, not pregnant or breastfeeding, willing to use contraception, and able to provide consent. Excluded are those with certain medical conditions, recent major surgery or immunotherapy treatment.

Inclusion Criteria

You need to have at least one spot that can be measured to see how the treatment is working.

I have been diagnosed with osteosarcoma.

My sarcoma hasn't responded to or I can't tolerate the usual treatment.

Exclusion Criteria

Any condition that, in the opinion of the investigator or sponsor, would interfere with evaluation of the investigational product or interpretation of subject safety or study results

I have had a blood clot in the last 3 months.

You have had a diagnosed autoimmune disease in the past 2 years, unless there are special circumstances.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive oleclumab IV over 1 hour every 2 weeks for 5 doses, then every 4 weeks thereafter, and durvalumab IV over 1 hour every 4 weeks. Cycle repeats every 28 days in the absence of disease progression or unacceptable toxicity.

Up to 4 months

Every 2 weeks initially, then every 4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, with follow-up at 30 days, and then every 3 months for up to 5 years.

Up to 5 years

Every 3 months

Treatment Details

Interventions

• Durvalumab
• Oleclumab

Trial Overview The trial is testing oleclumab and durvalumab—two monoclonal antibodies—to see if they can help the immune system fight sarcoma that's hard to treat because it came back or spread. It's a phase II study which means it’s checking how well these drugs work and their safety.

Participant Groups

Group I: Treatment (oleclumab, durvalumab) Experimental Treatment 2 Interventions

Patients receive oleclumab IV over 1 hour every 2 weeks for 5 doses, then every 4 weeks thereafter. Patients also receive durvalumab IV over 1 hour every 4 weeks. Cycle repeat every 28 days in the absence of disease progression or unacceptable toxicity.

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

Approved in European Union as Imfinzi for:

• Locally advanced, unresectable non-small cell lung cancer (NSCLC)

Approved in United States as Imfinzi for:

• Extensive-stage small cell lung cancer (ES-SCLC)
• Limited-stage small cell lung cancer (LS-SCLC)
• Locally advanced or metastatic urothelial carcinoma

Approved in Japan as Imfinzi for:

• Not specified in provided sources

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

Durvalumab is an FDA-approved monoclonal antibody that enhances T-cell responses against cancer by blocking the PD-L1 pathway, specifically for patients with advanced urothelial carcinoma who have progressed after platinum-based chemotherapy.

The drug is currently being tested in phase III trials for various cancers, including lung and head and neck cancers, indicating its potential broad application in oncology beyond urothelial carcinoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab: First Global Approval. Syed, YY.[2022]

Durvalumab, a PD-L1 inhibitor, has been shown to be safe for patients with various solid tumors, with common side effects including pruritus and fatigue, based on a meta-analysis of 17 studies involving 1,529 patients.

Higher levels of PD-L1 expression in tumors are linked to better treatment responses to durvalumab, indicating that PD-L1 could serve as a useful biomarker for predicting the drug's efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of durvalumab (MEDI4736) in various solid tumors. Yang, H., Shen, K., Zhu, C., et al.[2022]

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 study of 121 patients with stage III non-small cell lung cancer treated with durvalumab, those with over 50% PD-L1 expression had significantly better outcomes, with a 1-year survival rate of 97% compared to 73% and 78% for lower expression groups.

Higher PD-L1 expression (>50%) was strongly associated with improved progression-free survival and overall survival, indicating that PD-L1 levels could be a key factor in predicting the effectiveness of durvalumab treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tumor PD-L1 expression is associated with outcomes in stage III non-small cell lung cancer (NSCLC) patients treated with consolidation durvalumab. Jazieh, K., Gad, M., Saad, A., et al.[2022]

In the phase II ATLANTIC study, durvalumab demonstrated encouraging overall survival (OS) rates in heavily pretreated patients with advanced non-small cell lung cancer (NSCLC), with median OS ranging from 9.3 to 13.3 months depending on tumor characteristics.

The safety profile of durvalumab remained consistent with previous reports, showing no new safety concerns, indicating it is a tolerable treatment option for patients with advanced NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Final overall survival and safety update for durvalumab in third- or later-line advanced NSCLC: The phase II ATLANTIC study. Garassino, MC., Cho, BC., Kim, JH., et al.[2021]

In a phase I study involving 192 patients with advanced cancers, oleclumab, an anti-CD73 monoclonal antibody, demonstrated a manageable safety profile with treatment-related adverse events occurring in about 55% of patients, primarily fatigue, diarrhea, and rash.

While the overall objective response rate was low (0% during dose escalation and up to 9.5% in expansion cohorts), oleclumab showed pharmacodynamic activity by significantly reducing CD73 levels and enzymatic activity in tumor cells, indicating potential for further exploration in immunotherapy-resistant cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-in-human study of oleclumab, a potent, selective anti-CD73 monoclonal antibody, alone or in combination with durvalumab in patients with advanced solid tumors. Bendell, J., LoRusso, P., Overman, M., et al.[2023]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Durvalumab: First Global Approval. [2022]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Safety and efficacy of durvalumab (MEDI4736) in various solid tumors. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Durvalumab plus tremelimumab in advanced or metastatic soft tissue and bone sarcomas: a single-centre phase 2 trial. [2023]

4. China pubmed.ncbi.nlm.nih.gov

Tumor PD-L1 expression is associated with outcomes in stage III non-small cell lung cancer (NSCLC) patients treated with consolidation durvalumab. [2022]

5. Ireland pubmed.ncbi.nlm.nih.gov

Final overall survival and safety update for durvalumab in third- or later-line advanced NSCLC: The phase II ATLANTIC study. [2021]

6. Germany pubmed.ncbi.nlm.nih.gov

First-in-human study of oleclumab, a potent, selective anti-CD73 monoclonal antibody, alone or in combination with durvalumab in patients with advanced solid tumors. [2023]