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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate how well two immunotherapy drugs, oleclumab and durvalumab, work together to treat advanced sarcoma, a type of cancer that can recur, resist treatment, or spread to other parts of the body. The goal is to enhance the immune system's ability to fight the cancer and to slow the growth and spread of tumor cells. Individuals with sarcoma types such as angiosarcoma, dedifferentiated liposarcoma, or osteosarcoma, who have not responded to standard treatments, may be suitable candidates for this trial. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

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.

Is there any evidence suggesting that oleclumab and durvalumab are likely to be safe for humans?

Research has shown that the combination of oleclumab and durvalumab has been tested in various cancers. These studies indicate that while the treatment can be safe, its effectiveness varies across different cancer types.

Previous trials reported that using oleclumab and durvalumab together did not lead to serious safety issues. Most patients tolerate these treatments well. However, like most immunotherapies, some side effects can occur, such as tiredness, nausea, or skin reactions. It's important to remember that each person may react differently to the treatment.

Durvalumab alone is considered safe for many solid tumors. When combined with other drugs, like tremelimumab, it has shown a safety profile that patients can generally tolerate well.

Since this trial is in phase 2, the treatment has already passed some initial safety checks. This suggests the combination is reasonably safe for further testing, but monitoring for side effects remains necessary. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of oleclumab and durvalumab for advanced sarcoma because these treatments offer a fresh approach compared to standard chemotherapy options. Oleclumab works by targeting and inhibiting CD73, an enzyme that helps tumors evade the immune system. Durvalumab is an immune checkpoint inhibitor that blocks the PD-L1 protein, which often lets cancer cells hide from immune attack. Together, they aim to enhance the body's natural defenses against cancer, potentially improving outcomes for patients with advanced sarcoma.

What evidence suggests that oleclumab and durvalumab might be effective treatments for advanced sarcoma?

Researchers are investigating the use of a combination of two drugs, oleclumab and durvalumab, to treat advanced sarcoma in this trial. Oleclumab targets a protein called CD73, which helps cancer cells evade the immune system. By blocking CD73, oleclumab may enable the body to attack cancer cells more effectively. Durvalumab blocks another protein that prevents the immune system from fighting cancer. Some studies have shown limited success with this combination in different types of cancer. The trial aims to determine if it can help with sarcoma. Early results in similar cancers have been promising, particularly in slowing disease progression. ^{1 2 6 7 8}

Who Is on the Research Team?

Neeta Somaiah, MD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

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

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

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

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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]

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]

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 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]

Citations

1. withpower.com withpower.com/trial/phase-3-osteosarcoma-10-2020-2b250

Oleclumab + Durvalumab for Advanced Sarcoma In a phase 2 trial involving 62 patients with advanced or metastatic sarcoma, the combination of durvalumab and tremelimumab showed a promising progression-free ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04668300

NCT04668300 | Oleclumab and Durvalumab for the ... This phase II trial investigates how well oleclumab and durvalumab work in treating patients with sarcoma that has come back (recurrent) or does not respond ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04262388

Study Details | NCT04262388 | A Multi-Cancer, Multi-State ... Overall clinical activity (ORR) for oleclumab + durvalumab is minimal across tumor types and does not support further evaluation of this doublet. A Multi-Cancer ...

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.2018.36.15_suppl.4123

Safety, efficacy and pharmacodynamics (PD) of MEDI9447 ... Background: Oleclumab is a human mAb that binds to CD73 and inhibits production of immunosuppressive adenosine. This is a first-in-human study ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11508940/

PACIFIC-9: Phase III trial of durvalumab + oleclumab or ... PACIFIC-9 is a study that aims to recruit approximately 999 patients with stage III NSCLC for whom surgery is not an option and who have completed ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6038862/

Safety and efficacy of durvalumab (MEDI4736) in various ... Durvalumab is safe in patients with many solid cancers and, in combination with tremelimumab, it has a tolerable safety profile and is associated with improved ...

7. astrazenecaclinicaltrials.com astrazenecaclinicaltrials.com/study/D6070C00001/

MEDI9447 Alone and in Combination with MEDI4736 ... The purpose of this study is to Evaluate the Safety, Tolerability, Pharmacokinetics, Immunogenicity, and Antitumor Activity of MEDI9447 Alone and in ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT02503774

Study Details | NCT02503774 | MEDI9447 Alone and in ... Participants will receive oleclumab Dose 1 IV Q2W followed by durvalumab Dose 1 IV Q2W until confirmed disease progression, unacceptable toxicity, withdrawal of ...