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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the potential immune benefits of two drugs, durvalumab (an immunotherapy drug) and oleclumab (an experimental treatment), for individuals with surgically resectable pancreatic ductal adenocarcinoma (PDAC). The study aims to determine how these treatments, administered before surgery, might enhance the immune system's ability to combat the cancer. It seeks participants diagnosed with resectable PDAC who are in good physical health and can perform daily activities independently. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

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.

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

Research has shown that durvalumab is generally safe for people with various types of solid cancers and is usually well-tolerated, even when combined with other treatments. Early results suggest that combining oleclumab with durvalumab is also safe for different cancers, including pancreatic cancer.

In past studies, this combination caused few serious side effects. However, it was not very effective at shrinking tumors in many cases. While the drugs are generally safe, they might not always reduce tumors as much as expected.

For those considering joining a trial, it's important to know that these treatments are generally safe but may not work for everyone. Discuss the potential risks and benefits with a doctor to understand what it means for your specific situation. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Durvalumab and Oleclumab for pancreatic cancer because these treatments offer a novel approach compared to the current standard of care, which typically includes chemotherapy and surgery. Unlike traditional treatments, Durvalumab is an immunotherapy that enhances the body's immune response against cancer cells, targeting the PD-L1 protein to help the immune system recognize and attack tumors. Oleclumab, on the other hand, targets the CD73 enzyme, which is involved in suppressing the immune response, thereby potentially boosting the effectiveness of Durvalumab. This dual-action strategy could lead to more effective treatment outcomes by harnessing the body's own defenses to fight cancer.

What evidence suggests that this trial's treatments could be effective for pancreatic cancer?

Research has shown that combining durvalumab and oleclumab might offer a promising treatment for certain cancers. Some studies have found this combination to be generally safe and effective. Although its overall effectiveness has been limited across various cancers, it has helped some patients, such as those with lung cancer, live longer without disease progression. In this trial, participants will receive durvalumab and oleclumab to assess its potential benefits in pancreatic cancer, building on positive results observed in other cancers. ^{1 2 6 7 8}

Who Is on the Research Team?

Malcolm Moore, MD

Principal Investigator

Princess Margaret Cancer Centre/University Health Network

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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]

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]

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]

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]

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. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39106081/

A Phase Ib/II Randomized Clinical Trial of Oleclumab with ... Combining oleclumab (CD73 inhibitor) and durvalumab with chemotherapy may identify an effective treatment option.

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

Safety, efficacy and pharmacodynamics (PD) of MEDI9447 ... Conclusions: Treatment with oleclumab and durvalumab had a manageable safety profile and PD consistent with mechanism of action. Combination ...

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. asco.org asco.org/abstracts-presentations/ABSTRACT228203

Safety, efficacy and pharmacodynamics (PD) of MEDI9447 ... Treatment is ongoing for 1 CRC (322 days) and 2 panc pts (140 and 182 days). Conclusions: Treatment with oleclumab and durvalumab had a manageable safety ...

5. astrazeneca-us.com astrazeneca-us.com/media/press-releases/2021/imfinzi-combined-with-novel-immunotherapies-improved-clinical-outcomes-for-patients-with-unresectable-stage-iii-non-small-cell-lung-cancer-09172021.html

IMFINZI combined with novel immunotherapies improved ... The 10-month PFS rate was 64.8% for the durvalumab plus oleclumab combination and 72.7% for durvalumab plus monalizumab, versus 39.2% with ...

6. astrazenecaclinicaltrials.com astrazenecaclinicaltrials.com/study/D6070C00005

MEDI9447(Oleclumab) Pancreatic Chemotherapy ... The objective of this study is to evaluate the safety, tolerability, and antitumor activity of oleclumab (MEDI9447) in combination with or without durvalumab ...

7. 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 ...

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

Study Details | NCT02503774 | MEDI9447 Alone and in ... Participants with previously treated pancreatic adenocarcinoma will receive oleclumab Dose 4 IV Q2W followed by durvalumab Dose 1 IV Q2W until confirmed ...