AZD9291 Combinations for Non-Small Cell Lung Cancer

Not currently recruiting at 49 trial locations
Age: 18+
Sex: Any
Trial Phase: Phase 1
Sponsor: AstraZeneca
Must be taking: EGFR TKIs
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and initial effectiveness of combining AZD9291, a targeted therapy, with either AZD6094 or selumetinib for advanced lung cancer. It targets individuals with non-small cell lung cancer (NSCLC) who have a specific EGFR mutation and whose condition has worsened despite previous treatment. Participants must have an EGFR mutation responsive to certain treatments and must have experienced disease progression on previous EGFR therapies like gefitinib or erlotinib. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

Will I have to stop taking my current medications?

The trial requires stopping certain medications before starting the study. You must stop taking EGFR TKIs (like erlotinib or gefitinib) about 8 days before the first dose and avoid certain other medications and supplements that affect liver enzymes at least 3 weeks prior.

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

Previous studies have generally found AZD9291 (osimertinib) to be safe and well-tolerated. Research suggests that combining it with AZD6094 (savolitinib) is safe for patients with certain types of lung cancer. Other studies have shown that AZD6094, often used with other drugs, is safe on its own.

For the combination of AZD9291 and selumetinib, early findings suggest it is likely safe, though more research is needed to confirm this. Selumetinib has been tested in various cancer treatments and is generally considered safe when used correctly.

However, a significant safety concern arises with AZD9291 when combined with MEDI4736. This combination previously led to more cases of interstitial lung disease (a condition affecting lung tissue) and pneumonitis (lung inflammation). Due to these safety concerns, this combination is no longer under study.

Overall, while some combinations show promising safety results, the AZD9291 and MEDI4736 pairing has shown notable risks and is no longer being researched. Participants should discuss potential risks with their healthcare provider before joining any trial.12345

Why are researchers excited about this trial's treatments?

Researchers are excited about AZD9291 combinations for non-small cell lung cancer (NSCLC) because they offer a fresh approach to treatment compared to traditional therapies like chemotherapy and targeted therapies such as EGFR inhibitors. Unlike existing options, AZD9291 targets specific mutations in the EGFR gene, which are often responsible for resistance to first-line treatments. When combined with AZD6094 or selumetinib, AZD9291 may enhance the treatment's effectiveness by addressing different pathways involved in cancer growth. This multi-faceted attack on cancer cells has the potential to improve outcomes for patients who have limited options after initial therapies fail.

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

Research has shown that AZD9291, also known as osimertinib, holds promise for treating non-small cell lung cancer (NSCLC) with specific EGFR mutations. Studies have found that patients with certain resistant mutations experienced an average of 9.6 months before cancer progression. In this trial, researchers are testing AZD9291 in combination with selumetinib, which targets specific cancer cell pathways. Early lab tests indicate better cancer cell inhibition with this combination. Another arm of this trial involves AZD9291 combined with savolitinib (AZD6094), which targets a protein called MET, known to be overly active in some cancers. This combination has shown effectiveness in lung cancer. These findings suggest these treatments may be effective against certain advanced lung cancers.12367

Who Is on the Research Team?

PA

Pasi A Jänne, MD, PhD

Principal Investigator

Dana-Faber Cancer Institute

Are You a Good Fit for This Trial?

Adults with advanced lung cancer and specific EGFR mutations who've seen their disease progress on previous EGFR TKI treatments like gefitinib or erlotinib. They must have at least one measurable lesion, be able to take oral meds, and have good organ function. Pregnant women, those with certain heart conditions or active infections, and patients recently on other cancer therapies are excluded.

Inclusion Criteria

My lung cancer has a specific EGFR mutation.
Signed informed consent
My cancer progressed despite treatment with drugs like gefitinib or erlotinib.
See 9 more

Exclusion Criteria

I do not have stomach or intestine problems affecting medication absorption.
I have previously been treated with a specific type of lung cancer medication.
I am not taking any strong CYP3A4 inducers for the last 3 weeks.
See 19 more

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Combination Dose Finding

Participants receive AZD9291 in combination with novel therapeutics to determine optimal dosing and schedule

6-12 weeks
Regular visits for safety monitoring and dose adjustments

Dose Expansion

Further evaluation of safety and tolerability of the determined combination dose

Ongoing
Visits every 6 weeks for tumor response evaluation

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

  • AZD6094
  • AZD9291
  • Selumetinib
Trial Overview The trial is testing the safety and effectiveness of AZD9291 in combination with other drugs (AZD6094 or selumetinib) for treating advanced lung cancer. It's exploring different combinations to see which works best against tumors that have a particular mutation making them resistant to standard treatments.
How Is the Trial Designed?
4Treatment groups
Experimental Treatment
Group I: SelumetinibExperimental Treatment4 Interventions
Group II: MEDI4736Experimental Treatment2 Interventions
Group III: AZD6094 (monotherapy)Experimental Treatment1 Intervention
Group IV: AZD6094Experimental Treatment4 Interventions

Find a Clinic Near You

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

This phase I/II clinical trial is investigating the safety and efficacy of a combination treatment involving selumetinib, tremelimumab, and durvalumab in 40 patients with previously treated, unresectable non-small-cell lung cancer (NSCLC).
The study aims to determine the maximum tolerated dose and progression-free survival, while also exploring biomarkers of response and resistance, which could help tailor future treatments for NSCLC patients.
Phase I/II Trial of Immunotherapy With Durvalumab and Tremelimumab With Continuous or Intermittent MEK Inhibitor Selumetinib in NSCLC: Early Trial Report.Gaudreau, PO., Lee, JJ., Heymach, JV., et al.[2021]
AZD9291 is effective for treating patients with T790M mutant non-small-cell lung cancer after failure of first-generation EGFR TKIs, but resistance to AZD9291 eventually develops, as seen in a case study of a female patient whose disease progressed after 6 months of treatment.
The patient's re-biopsy revealed a transformation of her lung adenocarcinoma to small cell lung cancer, indicating that this transformation may be a potential resistance mechanism to AZD9291, suggesting that treatments for small cell carcinoma could be considered in such cases.
Transformation to small-cell carcinoma as an acquired resistance mechanism to AZD9291: A case report.Li, L., Wang, H., Li, C., et al.[2022]
AZD2171, a potent inhibitor of vascular endothelial growth factor receptors, can be safely combined with standard chemotherapy (carboplatin and paclitaxel) in patients with advanced non-small-cell lung cancer, showing no dose-limiting toxicities at doses of 30 mg or 45 mg per day.
The combination treatment resulted in a 45% response rate, with tumor shrinkage observed in nearly all patients, indicating promising antitumor activity despite some manageable side effects like fatigue and diarrhea.
Phase I and pharmacokinetic study of daily oral AZD2171, an inhibitor of vascular endothelial growth factor tyrosine kinases, in combination with carboplatin and paclitaxel in patients with advanced non-small-cell lung cancer: the National Cancer Institute of Canada clinical trials group.Laurie, SA., Gauthier, I., Arnold, A., et al.[2015]

Citations

Landscape of Savolitinib Development for the Treatment of ...Non-small cell lung cancer (NSCLC) accounts for approximately 80% of all lung cancers with a low 5-year survival rate of about 22% [1,2]. Most ...
A phase II study of savolitinib (volitinib, AZD6094, HMPL ...This single-arm phase II study will evaluate the clinical efficacy and tolerability of savolitinib in pts with MET amplified mCRC.
Savolitinib: A Promising Targeting Agent for Cancer - PMCIn both preclinical and clinical studies, it has demonstrated efficacy in lung, kidney, and stomach cancers. Savolitinib is an oral anti-cancer medication taken ...
Savolitinib plus osimertinib in epidermal growth factor ...Savolitinib + osimertinib had activity in MET overexpressed/amplified EGFR-mutated NSCLC after progression on osimertinib.
Record History | ver. 4: 2022-09-21 | NCT03833440This table shows all the versions of this study record arranged in order by submitted date. To view one version of the study record, click the submitted ...
mutated advanced non-small cell lung cancer with MET oveSavolitinib plus osimertinib versus platinum-based doublet chemotherapy in participants with non-small cell lung cancer who have progressed on ...
Savolitinib plus osimertinib in epidermal growth factor ...Savolitinib 300 mg bid plus osimertinib demonstrated high, clinically meaningful and durable responses in patients with EGFR-mutated, advanced NSCLC.
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