Durvalumab + Oleclumab for Pancreatic Cancer

(DORA Trial)

Overseen By Malcolm Moore, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University Health Network, Toronto

Must not be taking: Immunosuppressants, Anticancer therapies

Disqualifiers: Autoimmune disorders, Hepatitis, 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: 3

Duration: 4 weeks

22 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a multi-site Canadian, window of opportunity study to evaluate the immune activity of durvalumab and oleclumab in resectable pancreatic ductal adenocarcinoma (PDAC) when given prior to surgery.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot have used any immunosuppressive medication within 14 days before starting the study, except for certain low-dose or specific types of steroids. It's best to discuss your current medications with the study team.

What data supports the effectiveness of the drug Durvalumab + Oleclumab for treating pancreatic cancer?

Durvalumab has shown promise in increasing survival rates and response rates in non-small cell lung cancer, and Oleclumab has been studied in combination with Durvalumab for advanced solid tumors, including pancreatic cancer, suggesting potential benefits in enhancing immune responses against cancer. ^{1 2 3 4 5}

Is the combination of Durvalumab and Oleclumab safe for humans?

Durvalumab has been studied in various cancers and generally shows acceptable safety, though some patients experience serious side effects like reduced appetite and diarrhea. Oleclumab, when combined with Durvalumab, has been tested in advanced cancers, and while specific safety data for pancreatic cancer is limited, the combination has been evaluated in other solid tumors. ^{1 4 6 7 8}

How is the drug Durvalumab + Oleclumab unique for treating pancreatic cancer?

Durvalumab + Oleclumab is unique because it combines two monoclonal antibodies that target different immune pathways to help the body's immune system fight cancer. Durvalumab blocks PD-L1, a protein that helps cancer cells evade the immune system, while Oleclumab targets CD73, which is involved in creating an immunosuppressive environment around tumors. ^{1 4 5 7 9}

Research Team

Malcolm Moore, MD

Principal Investigator

Princess Margaret Cancer Centre/University Health Network

Eligibility Criteria

This trial is for adults with a specific type of pancreatic cancer (PDAC) who are strong enough for surgery, weigh at least 35 kg, and have an expected lifespan of 12 weeks or more. They must not have had recent cancer treatments or certain heart issues, autoimmune diseases, infections like hepatitis or HIV, and can't be on immune-suppressing drugs. Women must avoid pregnancy during the trial.

Inclusion Criteria

My cancer is confirmed as pancreatic ductal adenocarcinoma.

I am fully active or can carry out light work.

I weigh at least 35 kilograms.

Exclusion Criteria

Concurrent enrolment in another therapeutic clinical study. Enrolment in observational studies will be allowed

You are allergic or have a strong sensitivity to the experimental product being tested.

I have severe swelling.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive durvalumab and oleclumab prior to surgical resection

4 weeks

3 visits (in-person)

Surgery

Participants undergo surgical resection of pancreatic ductal adenocarcinoma

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Durvalumab
• Oleclumab

Trial Overview The study tests two drugs—Durvalumab and Oleclumab—in patients before they undergo surgery for PDAC. It's conducted across multiple Canadian sites to see how these drugs affect the body's immune response against this type of cancer.

Participant Groups

Group I: Durvalumab and Oleclumab Experimental Treatment 2 Interventions

Durvalumab, 1500 mg x 1 dose and oleclumab 3000 mg x 2 doses every 2 weeks prior to surgical resection.

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?

University Health Network, Toronto

Lead Sponsor

Trials

1,555

Recruited

526,000+

Findings from Research

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]

Durvalumab, a PD-L1 inhibitor, has shown promising results in increasing progression-free survival and objective response rates in patients with inoperable and locally advanced stage III non-small cell lung cancer, based on interim results from a phase III trial.

The significant benefits observed suggest that durvalumab could potentially become the standard treatment for these patients in the United States.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab Promising for NSCLC. [2019]

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 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]

The combination of durvalumab and tremelimumab in cancer treatment is associated with a higher incidence of severe adverse events (32.6%) compared to durvalumab alone (23.8%), indicating increased safety concerns with the combination therapy.

Patients receiving the combination therapy also experienced higher rates of specific side effects such as diarrhea (15.6% vs. 8.1%), rash (11.1% vs. 6.5%), and treatment discontinuation (18% vs. 3%), highlighting the need for careful monitoring and patient counseling regarding these risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse Events and Tolerability of Combined Durvalumab and Tremelimumab versus Durvalumab Alone in Solid Cancers: A Systematic Review and Meta-Analysis. Fahmy, O., Ahmed, OAA., Khairul-Asri, MG., et al.[2023]

Durvalumab, an immunotherapy drug for non-small cell lung cancer (NSCLC), has shown significant activity and acceptable tolerability, especially in patients with at least 25% PD-L1 tumor expression, and has been established as a standard treatment following chemoradiation based on the PACIFIC study results.

While durvalumab is effective in wild-type EGFR and ALK patients, its efficacy is lower in those with EGFR mutations or ALK-positive status, highlighting the need for ongoing research into combination therapies and the management of treatment-related toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab for the treatment of non-small cell lung cancer. Mezquita, L., Planchard, D.[2019]

In a safety run-in phase of the DURIGAST PRODIGE 59 study involving 11 patients with advanced gastric or gastro-oesophageal junction adenocarcinoma, 63.6% experienced significant adverse events, primarily neutropenia, indicating a notable safety concern with the treatment combination.

The combination of FOLFIRI with Durvalumab and/or Tremelimumab showed an expected safety profile, allowing progression to the randomized phase II study, although careful monitoring for serious adverse events is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of FOLFIRI + Durvalumab +/- Tremelimumab in Second Line of Patients with Advanced Gastric Cancer: A Safety Run-In from the Randomized Phase II Study DURIGAST PRODIGE 59. Evrard, C., Aparicio, T., Soularue, E., et al.[2022]

In a study of 14 patients with stage III NSCLC receiving Atezolizumab after chemoradiotherapy, 57% developed pneumonitis, indicating a significant risk associated with this treatment approach.

The onset of pneumonitis occurred on average 2.45 months after starting Atezolizumab, suggesting that monitoring for this side effect is crucial in patients undergoing this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pneumonitis in Non-Small Cell Lung Cancer Patients Receiving Atezolizumab Post Chemo-Radiation. Saade, LJ., Tfayli, A.[2023]

References

1. 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]

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

Durvalumab Promising for NSCLC. [2019]

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

Durvalumab: First Global Approval. [2022]

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

Safety and efficacy of durvalumab (MEDI4736) in various solid tumors. [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. Switzerland pubmed.ncbi.nlm.nih.gov

Adverse Events and Tolerability of Combined Durvalumab and Tremelimumab versus Durvalumab Alone in Solid Cancers: A Systematic Review and Meta-Analysis. [2023]

7. England pubmed.ncbi.nlm.nih.gov

Durvalumab for the treatment of non-small cell lung cancer. [2019]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Safety of FOLFIRI + Durvalumab +/- Tremelimumab in Second Line of Patients with Advanced Gastric Cancer: A Safety Run-In from the Randomized Phase II Study DURIGAST PRODIGE 59. [2022]

9. Thailand pubmed.ncbi.nlm.nih.gov

Pneumonitis in Non-Small Cell Lung Cancer Patients Receiving Atezolizumab Post Chemo-Radiation. [2023]