AZD0171 + Durvalumab + Chemotherapy for Pancreatic Cancer

Recruiting at 36 trial locations

Overseen By AstraZeneca Clinical Study Information Center

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: AstraZeneca

Must not be taking: Immunosuppressants, Live vaccines

Disqualifiers: CNS metastasis, Thromboembolic event, Infection, 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

Compensation: Varies

Number of Visits: 1

Duration: Variable (until progression or toxicity)

126 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a new drug (AZD0171) and an existing drug (durvalumab) along with standard chemotherapy in patients with advanced pancreatic cancer. The goal is to see if this combination can help the immune system fight the cancer while also killing cancer cells directly.

Will I have to stop taking my current medications?

The trial requires that you stop using immunosuppressive medications at least 14 days before starting the study treatment. If you are on any anticancer therapy, you must also stop before the first dose of the study intervention.

What data supports the effectiveness of the drug combination AZD0171, Durvalumab, and Chemotherapy for Pancreatic Cancer?

Research shows that nab-paclitaxel (Abraxane) combined with gemcitabine significantly improves survival in patients with advanced pancreatic cancer compared to gemcitabine alone. This suggests that the chemotherapy component of the treatment may be effective in treating pancreatic cancer. ^{1 2 3 4 5}

What safety data exists for the combination of AZD0171, Durvalumab, and Chemotherapy in humans?

Nab-paclitaxel (Abraxane), a form of chemotherapy used in the combination, has been shown to have a different toxicity profile than other forms of paclitaxel, with a lower rate of severe neutropenia (a condition where there is a low count of a type of white blood cell). It has been used in various cancer treatments, including pancreatic cancer, and is generally considered safe when combined with other drugs like gemcitabine. ^{1 2 4 6 7}

How is the drug AZD0171 + Durvalumab + Chemotherapy unique for pancreatic cancer?

This treatment combines AZD0171, an investigational drug, with Durvalumab (an immune therapy that helps the body's immune system attack cancer cells) and standard chemotherapy drugs Gemcitabine and Nab-paclitaxel. This combination is unique because it integrates an immune therapy with chemotherapy, potentially offering a new approach to treating pancreatic cancer, which has limited effective treatment options. ^{1 2 3 5 8}

Eligibility Criteria

This trial is for adults with metastatic pancreatic cancer who are in good physical condition (ECOG 0 or 1) and have a specific immune score. They must have at least one measurable tumor lesion, weigh over 35 kg, and provide tissue samples. Excluded are those with active infections, recent serious heart issues, other cancers, immunosuppressive treatments within the last two weeks, certain autoimmune diseases or prior cancer therapies.

Inclusion Criteria

All participants must consent to providing sufficient archival specimen taken during metastatic stage or fresh tumor specimens for tumoral CD8+ T cell testing for enrollment

I am fully active or restricted in physically strenuous activity but can do light work.

My cancer shows a specific immune response.

Exclusion Criteria

I have brain metastases or spinal cord issues related to my cancer.

I don't have any major side effects from previous treatments, except for possible skin or hair issues, or controlled diabetes.

I have or had an autoimmune or inflammatory disorder.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

1 visit (in-person)

Treatment

Participants receive AZD0171 and durvalumab in combination with standard-of-care chemotherapy until progressive disease or unacceptable toxicity

Variable (until progression or toxicity)

Regular visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 24 months

Periodic visits (in-person)

Pharmacokinetics and Immunogenicity Assessment

Assessment of PK profile and immunogenicity of AZD0171 and durvalumab

Up to Day 90 post last dose

Treatment Details

Interventions

• AZD0171
• Durvalumab
• Gemcitabine
• Nab-paclitaxel

Trial Overview The study tests AZD0171 combined with Durvalumab and standard chemotherapy drugs Gemcitabine and Nab-paclitaxel in patients with advanced pancreatic cancer. It aims to assess safety, how the body processes these drugs (pharmacokinetics), and their effectiveness against tumors.

Participant Groups

Group I: AZD0171 + Durvalumab + chemotherapy Experimental Treatment 4 Interventions

Participants will receive AZD0171 (intravenous \[IV\]) along with durvalumab (IV) in combination with standard-of-care chemotherapy IV (gemcitabine and nab-paclitaxel).

Who Is Running the Clinical Trial?

AstraZeneca

Lead Sponsor

Trials

4,491

Recruited

290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Findings from Research

In the NAPOLI 3 study involving 770 patients with metastatic pancreatic ductal adenocarcinoma, the NALIRIFOX treatment regimen resulted in a median overall survival of 11.1 months, which was significantly longer than the 9.2 months observed with the nab-paclitaxel and gemcitabine combination.

Both treatment groups experienced a high rate of grade 3 or higher adverse events (87% for NALIRIFOX and 86% for nab-paclitaxel-gemcitabine), indicating that while NALIRIFOX may improve survival, it does not significantly increase the risk of severe side effects compared to the standard treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

NALIRIFOX versus nab-paclitaxel and gemcitabine in treatment-naive patients with metastatic pancreatic ductal adenocarcinoma (NAPOLI 3): a randomised, open-label, phase 3 trial. Wainberg, ZA., Melisi, D., Macarulla, T., et al.[2023]

In a study involving 221 patients with metastatic pancreatic ductal adenocarcinoma and poor performance status, the combination of NAB-paclitaxel and gemcitabine was found to be well tolerated, with manageable side effects such as anemia and neutropenia.

Both dosing regimens of NAB-paclitaxel (100 mg/m2 and 125 mg/m2) showed similar efficacy, with comparable response rates and median progression-free survival, indicating that this treatment is effective for fragile patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I/II Trial to Evaluate the Efficacy and Safety of Nanoparticle Albumin-Bound Paclitaxel in Combination With Gemcitabine in Patients With Pancreatic Cancer and an ECOG Performance Status of 2. Macarulla, T., Pazo-Cid, R., Guillén-Ponce, C., et al.[2022]

The combination of nab-paclitaxel, gemcitabine, and capecitabine was found to be well tolerated in a phase I study with 15 patients, establishing a maximum-tolerated dose (MTD) but showing only modest antitumor activity in metastatic pancreatic cancer.

Despite the regimen being generally safe, with a low incidence of severe hematologic toxicities, only 14.3% of patients had a partial response, indicating that optimizing dose intensity may be crucial for improving treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I trial of nab-paclitaxel, gemcitabine, and capecitabine for metastatic pancreatic cancer. Ko, AH., Truong, TG., Kantoff, E., et al.[2022]

In a small study of 6 women with heavily pretreated HER2-negative metastatic breast cancer, the combination of nab-paclitaxel (nab-P) and bevacizumab (B), with or without gemcitabine (G), showed promising safety and preliminary efficacy, with only one patient experiencing significant toxicity.

Out of the 6 patients, 2 achieved partial responses and 4 had stable disease, indicating that this combination therapy may be effective, warranting further investigation in a formal phase II trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel albumin-bound particles (abraxane) in combination with bevacizumab with or without gemcitabine: early experience at the University of Miami/Braman Family Breast Cancer Institute. Lobo, C., Lopes, G., Silva, O., et al.[2022]

In a study of 80 Italian patients with metastatic pancreatic cancer, treatment with nab-paclitaxel in combination with gemcitabine resulted in a median overall survival of 8 months and a median progression-free survival of 5 months, indicating its efficacy.

Nab-paclitaxel was well-tolerated and led to significant pain relief, with reductions in the tumor marker CA 19-9 correlating positively with overall survival, suggesting it may be a useful predictor of treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical efficacy of nab-paclitaxel in patients with metastatic pancreatic cancer. De Luca, R., Blasi, L., Alù, M., et al.[2022]

The combination of nab-paclitaxel (Abraxane) and the fusion protein hIL15-ABD significantly reduced tumor size by 40%-60% in murine models of pancreatic ductal adenocarcinoma (PDAC), indicating enhanced efficacy compared to vehicle treatment.

This combination therapy increased the presence of active immune cells, such as CD8+ T cells and M1 macrophages, while reducing immunosuppressive cells in the tumor microenvironment, suggesting a mechanism that enhances anticancer immune responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Synergistic effect of Abraxane that combines human IL15 fused with an albumin-binding domain on murine models of pancreatic ductal adenocarcinoma. Hsu, FT., Tsai, CL., Chiang, IT., et al.[2022]

The maximum tolerated doses (MTD) of ABI-007 in combination with carboplatin were determined to be 300 mg/m², 100 mg/m², and 125 mg/m² for three different treatment schedules, indicating a well-defined dosing strategy for future studies.

The combination therapy was well tolerated with a lower incidence of severe neutropenia compared to traditional solvent-based paclitaxel, showing promising activity against various solid tumors, including lung and breast cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I and pharmacokinetic trial of carboplatin and albumin-bound paclitaxel, ABI-007 (Abraxane) on three treatment schedules in patients with solid tumors. Stinchcombe, TE., Socinski, MA., Walko, CM., et al.[2018]

A study of 5465 patients with advanced pancreatic cancer in Ontario showed that the introduction of new chemotherapy regimens, GEMNAB and FOLFIRINOX, significantly improved overall survival rates over time, with median survival increasing from 5.6 months to 7.6 months between 2008 and 2018.

FOLFIRINOX was found to provide better overall survival compared to GEMNAB, particularly in younger and healthier patients, while GEMNAB still showed improved survival compared to the older standard treatment, gemcitabine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Association of Drug-Funding Reimbursement With Survival Outcomes and Use of New Systemic Therapies Among Patients With Advanced Pancreatic Cancer. Raphael, MJ., Raskin, W., Habbous, S., et al.[2023]

References

1. England pubmed.ncbi.nlm.nih.gov

NALIRIFOX versus nab-paclitaxel and gemcitabine in treatment-naive patients with metastatic pancreatic ductal adenocarcinoma (NAPOLI 3): a randomised, open-label, phase 3 trial. [2023]

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

Phase I/II Trial to Evaluate the Efficacy and Safety of Nanoparticle Albumin-Bound Paclitaxel in Combination With Gemcitabine in Patients With Pancreatic Cancer and an ECOG Performance Status of 2. [2022]

3. Germany pubmed.ncbi.nlm.nih.gov

A phase I trial of nab-paclitaxel, gemcitabine, and capecitabine for metastatic pancreatic cancer. [2022]

4. France pubmed.ncbi.nlm.nih.gov

Paclitaxel albumin-bound particles (abraxane) in combination with bevacizumab with or without gemcitabine: early experience at the University of Miami/Braman Family Breast Cancer Institute. [2022]

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

Clinical efficacy of nab-paclitaxel in patients with metastatic pancreatic cancer. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Synergistic effect of Abraxane that combines human IL15 fused with an albumin-binding domain on murine models of pancreatic ductal adenocarcinoma. [2022]

7. Germany pubmed.ncbi.nlm.nih.gov

Phase I and pharmacokinetic trial of carboplatin and albumin-bound paclitaxel, ABI-007 (Abraxane) on three treatment schedules in patients with solid tumors. [2018]

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

The Association of Drug-Funding Reimbursement With Survival Outcomes and Use of New Systemic Therapies Among Patients With Advanced Pancreatic Cancer. [2023]