AZD8701 + Durvalumab for Solid Cancers

Recruiting at 16 trial locations

Overseen By AZ Breast Cancer Study Navigators

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: AstraZeneca

Must not be taking: Immunosuppressants, Anticoagulants

Disqualifiers: Autoimmune disorders, Cardiac disease, Covid-19, others

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

Compensation: Varies

Number of Visits: 8701

Duration: Up to 2 years

60 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a new drug, AZD8701, alone and with an existing drug, Durvalumab, in adults with advanced cancers. The goal is to see if these treatments can stop cancer growth or help the immune system fight the cancer. The study focuses on patients whose cancers are hard to treat or have responded to similar treatments before. Durvalumab is a drug that helps the immune system fight cancer and has been used with other treatments to help patients live longer.

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

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot use immunosuppressive medication within 14 days before the first dose, and you must not be on any concurrent cancer treatments.

What data supports the effectiveness of the drug AZD8701 + Durvalumab for solid cancers?

Durvalumab, a component of the treatment, has shown effectiveness in treating various solid tumors, including non-small cell lung cancer and urothelial carcinoma, by enhancing the immune system's response against cancer cells. It has been approved for use in certain cancers and is being tested in combination with other drugs, showing promising results in ongoing trials. ^{1 2 3 4 5}

Is the combination of AZD8701 and Durvalumab safe for treating solid cancers?

Durvalumab, also known as Imfinzi or MEDI4736, has been shown to have a manageable safety profile in various solid tumors, including non-small-cell lung cancer. When combined with other drugs, such as tremelimumab, the incidence of severe side effects was higher compared to durvalumab alone, with common issues like reduced appetite and diarrhea. However, it is generally considered to have acceptable tolerability in advanced cancer patients. ^{1 2 3 5 6}

What makes the drug AZD8701 + Durvalumab unique for treating solid cancers?

The combination of AZD8701 and Durvalumab is unique because it targets the immune system to fight cancer, with Durvalumab blocking PD-L1, a protein that helps cancer cells evade the immune system. This approach is different from traditional chemotherapy as it aims to enhance the body's own immune response against tumors. ^{1 2 4 5 7}

Eligibility Criteria

Adults with advanced solid tumors, including various cancers like lung, breast, and melanoma. They must have a tumor sample available, weigh over 35 kg, and have tried standard treatments without success or no options exist. Participants should be in relatively good health (ECOG 0-1), not pregnant or breastfeeding, willing to use contraception if of childbearing potential, and free from significant heart disease or active COVID-19.

Inclusion Criteria

You need to provide a recent or past sample of your tumor for the study.

You weigh more than 35 kilograms.

The study is comprised of 2 main parts Monotherapy (AZD8701) and Combined Therapy (AZD8701 and Durvalumab).

Exclusion Criteria

You have a serious heart condition.

Receipt of the last dose of anticancer therapy within 5 half-lives or ≤ 21 days prior to the first dose of study

Female participants who are pregnant or breastfeeding or male and female participants of reproductive potential who are not willing to employ effective birth control

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive AZD8701 intravenously, on Day 1, 3, 5, and 8, then weekly for a maximum of 2 years. In combination therapy, participants also receive durvalumab monthly.

Up to 2 years

Weekly visits for AZD8701, monthly visits for durvalumab

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments of pharmacokinetics and pharmacodynamics.

105 days after last dose

Open-label extension (optional)

Participants may opt into continuation of treatment long-term

Long-term

Treatment Details

Interventions

• AZD8701
• Durvalumab

Trial Overview The trial is testing AZD8701 alone and combined with Durvalumab for safety and effectiveness against certain advanced solid tumors. It will look at how the body processes these drugs (pharmacokinetics/dynamics) as well as their ability to provoke an immune response (immunogenicity) and fight cancer cells.

Participant Groups

Group I: Monotherapy Experimental Treatment 1 Intervention

Participants will receive AZD8701 intravenously, on Day 1, 3, 5 and 8 and then weekly for a maximum of 2 years.

Group II: Combination Therapy Experimental Treatment 2 Interventions

Participants will receive AZD8701 (intravenously, on Day 1, 3, 5 and 8 and then weekly) and durvalumab (MEDI4736) intravenously monthly for a maximum of 2 years.

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

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, a PD-L1 blocking antibody, has shown clinical efficacy and a manageable safety profile in treating advanced non-small-cell lung cancer, especially in patients with ≥25% PD-L1 expression.

The drug is being evaluated in various treatment settings, including as a monotherapy and in combination with other therapies, showing promising results particularly after chemoradiation, although lower response rates were noted in patients with EGFR and ALK mutations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab in non-small-cell lung cancer patients: current developments. Mezquita, L., Planchard, D.[2018]

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]

The combination of MEDI0680 and durvalumab was found to be safe and tolerable in patients with advanced clear-cell renal cell carcinoma, but it did not show improved efficacy compared to nivolumab alone, with objective response rates of 16.7% for the combination and 23.8% for nivolumab.

Both treatment groups had a median progression-free survival of 3.6 months, and a notable percentage of patients (23.8% in the combination group) discontinued treatment due to adverse events, highlighting the need for careful monitoring of side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Randomized Phase II Study of MEDI0680 in Combination with Durvalumab versus Nivolumab Monotherapy in Patients with Advanced or Metastatic Clear-cell Renal Cell Carcinoma. Voss, MH., Azad, AA., Hansen, AR., 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]

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 58 patients with advanced solid tumors, the combination of MEDI0562 with either durvalumab or tremelimumab showed moderate toxicity, with 74.1% and 67.7% of patients reporting treatment-related adverse events, respectively.

While three patients showed a partial response to the MEDI0562 and durvalumab combination, the study did not demonstrate clear efficacy signals, indicating that further research is needed to evaluate the effectiveness of these combinations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Tolerability of MEDI0562, an OX40 Agonist mAb, in Combination with Durvalumab or Tremelimumab in Adult Patients with Advanced Solid Tumors. Goldman, JW., Piha-Paul, SA., Curti, B., et al.[2022]

References

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

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

2. England pubmed.ncbi.nlm.nih.gov

Durvalumab in non-small-cell lung cancer patients: current developments. [2018]

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

Durvalumab: First Global Approval. [2022]

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

A Randomized Phase II Study of MEDI0680 in Combination with Durvalumab versus Nivolumab Monotherapy in Patients with Advanced or Metastatic Clear-cell Renal Cell Carcinoma. [2023]

5. England pubmed.ncbi.nlm.nih.gov

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

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

Safety and Tolerability of MEDI0562, an OX40 Agonist mAb, in Combination with Durvalumab or Tremelimumab in Adult Patients with Advanced Solid Tumors. [2022]