AZD8701 + Durvalumab for Solid Cancers

No longer recruiting at 18 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and effectiveness of a new treatment for certain advanced solid cancers. The treatment uses a drug called AZD8701, given alone or with another drug, Durvalumab (also known as Imfinzi). The study targets solid tumors, including certain types of lung, breast, and kidney cancers. Individuals with these cancers who have not responded to standard treatments might be suitable for this trial. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the chance to be among the first to receive it.

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.

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

Research has shown that AZD8701 has been tested for safety, though it has not demonstrated strong effects yet. Reported side effects are generally manageable. This treatment blocks certain genetic instructions in cancer cells.

For those considering AZD8701 with durvalumab, additional safety information is available. Durvalumab, already used for other cancers, has a safety profile that patients usually tolerate well. It has been applied in various solid tumors, such as lung cancer.

While these findings provide some insights, the study remains in its early stages. More research is necessary to fully understand the safety and effects of these treatments when used together. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about AZD8701 and Durvalumab for treating solid cancers because these drugs offer unique approaches compared to existing treatments. Most current therapies rely on traditional chemotherapy or radiation, which can have widespread effects on healthy cells. In contrast, AZD8701 is an innovative compound that targets specific cancer cell mechanisms to potentially minimize damage to normal cells. Durvalumab, an immune checkpoint inhibitor, works by boosting the immune system's ability to recognize and fight cancer cells. Together, these treatments aim to offer a more targeted and potentially effective approach to cancer care.

What evidence suggests that this trial's treatments could be effective for solid cancers?

Research has shown that AZD8701, which participants in this trial may receive as monotherapy, has produced promising results. Specifically, 24.4% of patients experienced stable disease for at least 16 weeks, and 15.6% for at least 24 weeks, indicating the cancer did not worsen for a significant period.

In this trial, some participants will receive a combination of AZD8701 with Durvalumab. Durvalumab has proven effective in treating several types of solid tumors, such as those in the lungs and bladder. Together, these treatments might better control the growth of certain solid tumors. ^{2 3 4 5 6}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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 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]

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, 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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11995004/

AZD8701, an Antisense Oligonucleotide Targeting FOXP3 ... We report a phase I study of AZD8701 alone or combined with durvalumab in patients with advanced solid tumors.

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39937271/

AZD8701, an Antisense Oligonucleotide Targeting FOXP3 ... With AZD8701 monotherapy, 24.4% and 15.6% of the patients had stable disease for ≥16 and ≥24 weeks, respectively; one patient treated with ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04504669

NCT04504669 | First Time in Human Study of AZD8701 ... A Phase I First-in-Human Study to Evaluate the Safety, Pharmacokinetics, Pharmacodynamics and Efficacy of AZD8701 Administered Intravenously as Monotherapy and ...

4. withpower.com withpower.com/trial/phase-1-head-and-neck-neoplasms-7-2020-0791b

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 ...

5. astrazenecaclinicaltrials.com astrazenecaclinicaltrials.com/study/D9950C00001

First time in Human Study of AZD8701 with or without ... The purpose of this study is to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, Immunogenicity and Antitumor Activity of AZD8701 ...

6. aacrjournals.org aacrjournals.org/clincancerres/article/31/8/1449/754529/AZD8701-an-Antisense-Oligonucleotide-Targeting

AZD8701, an Antisense Oligonucleotide Targeting FOXP3 ... Based on these efficacy data, which suggest that AZD8701 has limited activity and safety data, the planned dose-expansion parts of the study were not initiated.