AZD2936 for Non-Small Cell Lung Cancer

(ARTEMIDE-01 Trial)

Recruiting at 35 trial locations

Overseen By AstraZeneca Clinical Study Information Center

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: AstraZeneca

Must not be taking: Chemotherapy, Radiotherapy, Biologic, Hormonal

Disqualifiers: EGFR mutations, ALK fusion, others

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

Compensation: Varies

Number of Visits: Unknown

199 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a new medicine that helps the immune system fight severe lung cancer by stopping the cancer from hiding. It is aimed at adults with advanced lung cancer that cannot be removed by surgery.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, you cannot have any concurrent chemotherapy, radiotherapy, investigational, biologic, or hormonal therapy for cancer treatment while participating in the trial.

What data supports the effectiveness of the drug AZD2936 for treating non-small cell lung cancer?

Research on similar drugs like ZD1839 shows they can help improve symptoms and quality of life in patients with advanced non-small cell lung cancer by targeting specific molecular processes involved in cancer growth. Additionally, AZD2171, another related drug, has shown broad antitumor activity in preclinical models, suggesting potential effectiveness in treating this type of cancer. ^{1 2 3 4 5}

What safety data exists for AZD2936 or similar treatments in humans?

ZD1839, a similar treatment, showed manageable side effects like skin rash, nausea, vomiting, and diarrhea in early studies, with good tolerance in healthy volunteers. AZD9291, another related treatment, has been associated with rare but serious lung disease in some cases. ^{1 4 6 7 8}

Eligibility Criteria

Adults with advanced or metastatic non-small cell lung cancer (NSCLC) that can't be removed by surgery or cured with radiation, and who have seen their cancer progress after treatment. They must not have certain genetic mutations treatable by other drugs, no recent serious blood clots, no other cancers in the last 2 years, and no previous anti-TIGIT therapy.

Inclusion Criteria

Your PD-L1 levels have been tested and reported by your local laboratory.

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

My stage IV lung cancer cannot be cured with surgery or radiation.

Exclusion Criteria

My cancer has a specific genetic change that can be treated with targeted therapy.

I have not had any other cancer besides this one in the last 2 years.

I have not had a blood clot in the last 3 months.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive rilvegostomig IV monotherapy to determine the maximum tolerated dose

6 months

Regular visits at predefined intervals

Dose Expansion

Participants receive rilvegostomig IV monotherapy to further evaluate safety and efficacy

Approximately 2 years

Regular visits at predefined intervals

Follow-up

Participants are monitored for safety and effectiveness after treatment

90 days after the last dose

Treatment Details

Interventions

• AZD2936

Trial Overview The trial is testing AZD2936, a new bispecific antibody targeting two immune checkpoints: TIGIT and PD-1. It's for people whose NSCLC has worsened despite current treatments. The study aims to find out if this drug is safe and effective at controlling their cancer.

Participant Groups

Group I: Dose Expansion Part E: treatment Naive Squamous NSCLC Experimental Treatment 1 Intervention

Rilvegostomig IV monotherapy

Group II: Dose Expansion Part D: CPI Naive NSCLC Experimental Treatment 1 Intervention

Rilvegostomig IV monotherapy

Group III: Dose Expansion Part C: CPI Naive NSCLC Experimental Treatment 1 Intervention

Rilvegostomig IV monotherapy

Group IV: Dose Expansion Part B: CPI experienced NSCLC Experimental Treatment 1 Intervention

Rilvegostomig IV monotherapy

Group V: Dose Escalation Part A: Checkpoint inhibitor (CPI) experienced Non-small Cell Lung Cancer (NSCLC) Experimental Treatment 1 Intervention

Rilvegostomig Intravenous (IV) monotherapy

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 a study of 32 patients with non-small-cell lung cancer (NSCLC) treated with ZD1839 for over 90 days, the drug achieved a disease control rate of 56.25%, with 18.75% experiencing partial remission.

ZD1839 was associated with manageable side effects, including acneiform rash (31.25%) and diarrhea (18.75%), but notably did not cause interstitial lung disease, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinical observation of ZD1839 in treating 32 cases of non-small-cell lung cancer]. Zhang, L.[2018]

In a phase II trial involving 43 patients with FGFR-altered squamous cell lung cancer, the FGFR inhibitor AZD4547 was found to have an acceptable safety profile, with only a few grade 3 adverse events reported.

Despite its safety, AZD4547 showed minimal therapeutic activity, achieving confirmed partial responses in only 7% of patients, with a median progression-free survival of 2.7 months and overall survival of 7.5 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

SWOG S1400D (NCT02965378), a Phase II Study of the Fibroblast Growth Factor Receptor Inhibitor AZD4547 in Previously Treated Patients With Fibroblast Growth Factor Pathway-Activated Stage IV Squamous Cell Lung Cancer (Lung-MAP Substudy). Aggarwal, C., Redman, MW., Lara, PN., et al.[2022]

ZD1839, a targeted therapy that inhibits EGFR-associated tyrosine kinase activity, has shown efficacy in treating advanced non-small cell lung cancer (NSCLC) by disrupting tumor growth and survival mechanisms.

Clinical trials of ZD1839 not only assessed response rates but also focused on improving symptoms and quality of life for patients, highlighting its potential benefits beyond traditional chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inhibition of epidermal growth factor receptor and symptom improvement in advanced non-small cell lung cancer. Natale, RB.[2005]

ZD 1839, a treatment for Non-Small-Cell Lung Cancer (NSCLC), has shown activity against brain metastases in four reported cases, indicating potential efficacy in this challenging area.

The response of brain metastases to ZD 1839 suggests that it may be a promising therapeutic option for patients with NSCLC who develop brain metastases, although further studies are needed to confirm these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ZD 1839 in patients with brain metastases from non-small-cell lung cancer (NSCLC): report of four cases. Cappuzzo, F., Calandri, C., Bartolini, S., et al.[2023]

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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]

AZD9291, an EGFR-TKI used for treating non-small cell lung cancer, has a rare but serious side effect of inducing interstitial lung disease (ILD).

The case presented highlights the potential severity of ILD associated with AZD9291 treatment, emphasizing the need for awareness and monitoring in patients receiving this medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fatal interstitial lung disease associated with AZD9291. Deng, SM., Huang, JA., Chen, YB.[2022]

ZD 1839 is a specific inhibitor of the EGF receptor that effectively blocks cell signaling, leading to antiproliferative effects, particularly in non-small cell lung cancer, as shown in preclinical studies.

The drug has a long half-life of 27 to 41 hours, allowing for convenient single oral dosing, and has demonstrated manageable toxicity in phase I studies, with common side effects including skin rash, nausea, vomiting, and diarrhea.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Zd 1839 "Iressa"]. Meric, JB., Faivre, S., Monnerat, C., et al.[2018]

Shikonin, a natural compound that induces reactive oxygen species (ROS), enhances the antitumor effects of AZD9291 in non-small cell lung cancer (NSCLC) cells with wild-type EGFR, suggesting a potential new treatment strategy.

The combination of shikonin and AZD9291 increases apoptosis in NSCLC cells through ROS-mediated endoplasmic reticulum (ER) stress, indicating that targeting ROS could improve outcomes for patients with wtEGFR NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A natural anthraquinone derivative shikonin synergizes with AZD9291 against wtEGFR NSCLC cells through reactive oxygen species-mediated endoplasmic reticulum stress. Hu, X., Zhang, ZY., Wu, LW., et al.[2022]

References

1. China pubmed.ncbi.nlm.nih.gov

[Clinical observation of ZD1839 in treating 32 cases of non-small-cell lung cancer]. [2018]

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

SWOG S1400D (NCT02965378), a Phase II Study of the Fibroblast Growth Factor Receptor Inhibitor AZD4547 in Previously Treated Patients With Fibroblast Growth Factor Pathway-Activated Stage IV Squamous Cell Lung Cancer (Lung-MAP Substudy). [2022]

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

Inhibition of epidermal growth factor receptor and symptom improvement in advanced non-small cell lung cancer. [2005]

4. England pubmed.ncbi.nlm.nih.gov

ZD 1839 in patients with brain metastases from non-small-cell lung cancer (NSCLC): report of four cases. [2023]

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

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. [2015]

6. India pubmed.ncbi.nlm.nih.gov

Fatal interstitial lung disease associated with AZD9291. [2022]

7. France pubmed.ncbi.nlm.nih.gov

[Zd 1839 "Iressa"]. [2018]

8. Germany pubmed.ncbi.nlm.nih.gov

A natural anthraquinone derivative shikonin synergizes with AZD9291 against wtEGFR NSCLC cells through reactive oxygen species-mediated endoplasmic reticulum stress. [2022]