What side effects are associated with this type of intervention?

Treatments for solid tumors, particularly those involving immune checkpoint inhibitors like Durvalumab (PD-L1 inhibition), commonly result in immune-related adverse events such as pneumonitis, colitis, hepatitis, endocrinopathies, and skin reactions. STAT3 inhibitors, such as AZD9150, may cause side effects related to immune modulation and general chemotherapy-related toxicities, including fatigue, nausea, and hematologic abnormalities. Patients should discuss these potential side effects with their healthcare provider to manage and mitigate risks effectively.

What prior FDA approvals exist?

The FDA has approved several PD-1 and PD-L1 inhibitors for the treatment of solid tumors. Notable examples include Pembrolizumab (Keytruda) and Nivolumab (Opdivo), which are PD-1 inhibitors, and Atezolizumab (Tecentriq) and Durvalumab (Imfinzi), which are PD-L1 inhibitors. These drugs have been approved for various types of solid tumors, including non-small cell lung cancer (NSCLC), melanoma, and head and neck squamous cell carcinoma. While STAT3 inhibitors like AZD9150 are still under investigation, the use of immune checkpoint inhibitors targeting PD-1 and PD-L1 pathways has become a cornerstone in the treatment of advanced solid tumors.

What other types of research exist?

Promising alternatives for solid tumor treatment in 2024 include: 1) Pembrolizumab (PD-1 Inhibition) combined with chemotherapy, as shown in the KEYNOTE-062 study for gastric cancer. 2) Nivolumab (PD-1 Inhibition) combined with Ipilimumab (CTLA-4 Inhibition), which has demonstrated efficacy in various cancers including melanoma and renal cell carcinoma. 3) Relatlimab combined with Nivolumab, which has shown promising results in untreated advanced melanoma. These alternatives leverage immune checkpoint inhibition and combination strategies to enhance anti-tumor activity.

← Back to Search

Antisense Oligonucleotide

AZD9150 + Durvalumab and Chemotherapy for Solid Cancers

Phase 1

Waitlist Available

Research Sponsored by AstraZeneca

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Part A of the study will include patients that have histological confirmation of a solid malignancy [other than Hepatocellular Carcinoma (HCC)] that is refractory to standard therapy or for which no standard of care regimen currently exists

Part D of the study will include patients with histological confirmation of a solid malignancy (other than HCC) that are refractory to standard therapy of for which no standard of care regimen currently exists

Timeline

Screening 3 weeks

Treatment Varies

Follow Up through study completion (an average of 6 months). dose-limiting toxicities (dlts) will be assessed through 5 weeks for patients who do not receive chemotherapy or 3 weeks for patients receiving chemotherapy.

Awards & highlights

Study Summary

This trial is testing a new drug, AZD9150, to see if it is safe and works well against cancer. The trial will first test AZD9150 alone and then in combination with another drug, durvalumab, or with chemotherapy.

Who is the study for?

Adults over 18 with advanced solid tumors or non-small-cell lung cancer (NSCLC) that standard treatments can't help. They must have a life expectancy of at least 12 weeks, agree to genetic sampling, and meet certain health criteria. Women must not be pregnant and use birth control; men need contraception too. Participants should be fairly active and healthy overall (ECOG score of 0 or 1).Check my eligibility

What is being tested?

The trial is testing AZD9150 in combination with Durvalumab, alone or alongside chemotherapy drugs like Gemcitabine, Nab-paclitaxel, Cisplatin, Carboplatin, and 5-Flourouracil for their safety and effectiveness against advanced solid tumors including NSCLC.See study design

What are the potential side effects?

Possible side effects include reactions related to the immune system affecting organs, infusion-related reactions from the drug entering the body, fatigue, nausea or vomiting due to chemotherapy drugs used in combination therapy.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

Select...

I have a confirmed solid tumor cancer, not liver cancer, with no effective standard treatment left.

Select...

My cancer does not respond to standard treatments anymore.

Select...

I have a tumor that can be measured and has not been treated with radiation.

Select...

I am 18 years old or older.

Select...

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

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ through study completion (an average of 6 months). dose-limiting toxicities (dlts) will be assessed through 5 weeks for patients who do not receive chemotherapy or 3 weeks for patients receiving chemotherapy.

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~through study completion (an average of 6 months). dose-limiting toxicities (dlts) will be assessed through 5 weeks for patients who do not receive chemotherapy or 3 weeks for patients receiving chemotherapy.

This trial's timeline: 3 weeks for screening, Varies for treatment, and through study completion (an average of 6 months). dose-limiting toxicities (dlts) will be assessed through 5 weeks for patients who do not receive chemotherapy or 3 weeks for patients receiving chemotherapy. for reporting.

Treatment Details

Study Objectives

Outcome measures can provide a clearer picture of what you can expect from a treatment.

Primary outcome measures

Part A: Maximum Tolerated Dose (MTD) in subjects receiving AZD9150 plus durvalumab and AZD9150 plus durvalumab plus chemotherapy.

Part D: Area under the plasma concentration versus time curve at steady state [AUC(ss)] of AZD9150 administered once per week in combination with durvalumab.

Part D: Minimum plasma concentration at steady state [Ctrough (ss)] of AZD9150 administered once per week in combination with durvalumab.

Secondary outcome measures

Part A: AZD9150 anti-drug antibody titres

Part A: Area under the plasma concentration versus time curve (AUC) of AZD9150 after single-dose.

Part A: Area under the plasma concentration versus time curve [AUC(ss)] at steady state after multiple doses.

+27 more

Trial Design

7Treatment groups

Experimental Treatment

Group I: Arm D: AZD9150 SCExperimental Treatment2 Interventions

Part D will compare the single and steady state pharmacokinetics of AZD9150 given subcutaneously (SC) QW to AZD9150 given by IV QW in combination with durvalumab 1500 mg Q4W. Patients will be randomly assigned to either SC or IV AZD9150.

Group II: Arm D: AZD9150 IVExperimental Treatment2 Interventions

Group III: Arm A5Experimental Treatment4 Interventions

Patients will receive AZD9150 every two weeks (Q2W) plus durvalumab every three weeks (Q3W) plus carboplatin on Day 1 plus nab-paclitaxel on Days 1, 8, and 15 (every 3 weeks for up to 12-18 weeks). There will be a 1 week AZD9150 + chemotherapy lead-in prior to durvalumab dosing.

Group IV: Arm A4Experimental Treatment5 Interventions

Patients will receive AZD9150 every two weeks (Q2W) + durvalumab every three weeks (Q3W) + gemcitabine on Days 1 and 8. This regimen will be repeated every 3 weeks. In addition, the following will be added to the regimen: For cisplatin-eligible patients: cisplatin on Day 1 (every 3 weeks for up to 12-18 weeks); or For cisplatin ineligible patients: carboplatin on Day 1 and Day 8 (every 3 weeks for up to 12-18 weeks) There will be a 1 week AZD9150 + chemotherapy lead-in prior to durvalumab dosing.

Group V: Arm A3Experimental Treatment4 Interventions

Depending on the results of Arm A2, Arm A3 may not be conducted. If Arm A3 is conducted, patients will receive AZD9150 every two weeks (Q2W) + durvalumab every three weeks (Q3W) + cisplatin on Day 1 + 5-flourouracil (5-FU) over Days 1 to 4. This regimen will be repeated every 3 weeks for up to 18 weeks. There will be a 1 week AZD9150 + chemotherapy lead-in prior to durvalumab dosing.

Group VI: Arm A2Experimental Treatment4 Interventions

Patients will receive AZD9150 once weekly (QW) + durvalumab every three weeks (Q3W) + Cisplatin on Day 1 + 5-flourouracil (5-FU) on Days 1 to 4. This regimen will be repeated every 3 weeks for up to 18 weeks. There will be a 1 week AZD9150 + chemotherapy lead-in prior to durvalumab dosing.

Group VII: Arm A1Experimental Treatment2 Interventions

Patients will receive AZD9150 every two weeks (Q2W) + durvalumab every four weeks (Q4W). There will be a 1 week AZD9150 lead-in prior to durvalumab dosing.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Gemcitabine

2017

Completed Phase 3

~2070

Nab-paclitaxel

2014

Completed Phase 3

~2030

AZD9150

2018

Completed Phase 1

~120

Durvalumab

2017

Completed Phase 2

~3870

Cisplatin

2013

Completed Phase 3

~1940

Carboplatin

2014

Completed Phase 3

~6670

0 / 5Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The treatment of solid tumors often involves targeting specific molecular pathways that contribute to tumor growth and immune evasion. AZD9150 works by inhibiting STAT3, a transcription factor that promotes tumor cell survival, proliferation, and immune suppression. By blocking STAT3, AZD9150 can reduce tumor growth and enhance the immune system's ability to attack cancer cells. Durvalumab, on the other hand, is an immune checkpoint inhibitor that targets PD-L1, a protein that tumors use to protect themselves from immune attack. By inhibiting PD-L1, Durvalumab helps to restore the immune system's ability to recognize and destroy cancer cells. These mechanisms are crucial for patients with solid tumors as they offer a way to directly interfere with tumor growth and improve the body's natural immune response against cancer.

Expanding Therapeutic Options for Older Adults: Case-Based Updates in Breast and Lung Cancer.Recurrent glioma clinical trial, CheckMate-143: the game is not over yet.Emerging and mechanism-based therapies for recurrent or metastatic Merkel cell carcinoma.