AZD2936 for Non-Small Cell Lung Cancer

(ARTEMIDE-01 Trial)

Recruiting at 43 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

210 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment, AZD2936, to determine its safety and effectiveness for individuals with advanced or metastatic non-small cell lung cancer. It evaluates a special antibody, a protein used by the immune system, designed to target specific proteins involved in cancer growth. The trial includes different groups: some consist of participants who have tried certain treatments before, while others have not. Suitable candidates have advanced lung cancer that cannot be treated with surgery or radiation and may have undergone previous treatments. As a Phase 1, Phase 2 trial, it provides an opportunity to be among the first to receive a new treatment and helps assess its effectiveness in an initial group.

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.

Is there any evidence suggesting that AZD2936 is likely to be safe for humans?

Research has shown that rilvegostomig (AZD2936) is generally safe for individuals with advanced or spreading non-small cell lung cancer. In studies, patients who had already tried standard treatments received AZD2936. Most tolerated the treatment well, experiencing no severe side effects. Some encountered mild to moderate side effects, which are common with many cancer treatments.

Another study tested rilvegostomig combined with a different drug as an initial treatment for lung cancer patients. This study also demonstrated positive safety results, with manageable side effects.

These findings are promising, suggesting that rilvegostomig is reasonably safe. Ongoing trials aim to confirm these results and explore additional benefits of the treatment. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for non-small cell lung cancer?

Unlike the standard treatments for non-small cell lung cancer (NSCLC), which often include chemotherapy, targeted therapies, and immunotherapies, AZD2936 works differently by targeting specific pathways involved in cancer cell growth. Researchers are excited about AZD2936 because it employs Rilvegostomig, an innovative compound, administered intravenously, which may offer a new mechanism of action compared to existing options. This could potentially improve outcomes for patients, particularly those who have not responded well to current therapies. The treatment's unique approach and delivery method provide hope for more effective management of NSCLC, especially in patients with limited treatment options.

What evidence suggests that AZD2936 might be an effective treatment for non-small cell lung cancer?

Research has shown that rilvegostomig (AZD2936) could be a promising treatment for non-small cell lung cancer (NSCLC). This trial includes several treatment arms where participants receive rilvegostomig as an intravenous monotherapy. The treatment targets specific proteins, PD-1 and TIGIT, which usually prevent the immune system from fighting cancer effectively. Early results suggest that rilvegostomig is safe and effective, especially for patients who haven't used similar treatments before. Studies have reported positive responses in patients and a good safety record. This suggests that rilvegostomig might help the immune system attack cancer cells more effectively. ^{1 2 3 6 7}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

Citations

1. annalsofoncology.org annalsofoncology.org/article/S0923-7534(23)03314-8/fulltext

1446P Preliminary efficacy and safety of rilvegostomig ... Rilvegostomig is a bispecific, humanised IgG1 targeting PD-1 and TIGIT, receptors that suppress antitumour T cell activity. Initial data from the first-in-human ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.8521

First-line (1L) datopotamab deruxtecan (Dato-DXd) + ... Dato-DXd + rilvegostomig had encouraging activity as 1L treatment for pts with a/mNSCLC without AGAs, with responses seen in both histologies and across all PD ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04995523

NCT04995523 | A Study of AZD2936 Anti-TIGIT/Anti-PD-1 ... This is a Phase I/II study designed to evaluate if experimental anti-TIGIT/anti-PD-1 bispecific antibody rilvegostomig (AZD2936) is safe, tolerable and ...

4. lungcancerstoday.com lungcancerstoday.com/post/rilvegostomig-appears-safe-effective-for-cpi-naive-metastatic-nsclc

Rilvegostomig Appears Safe and Effective for CPI-naïve ... Rilvegostomig showed a favorable safety profile and encouraging preliminary efficacy in checkpoint inhibitor (CPI)-naïve patients with metastatic non-small- ...

5. oncodaily.com oncodaily.com/oncolibrary/artemide-01-trial

ARTEMIDE-01 Trial Demonstrates Promising Efficacy and ... The ARTEMIDE-01 trial (NCT04995523) represents the first-in-human study of rilvegostomig in patients with metastatic non-small cell lung cancer ...

6. asco.org asco.org/abstracts-presentations/ABSTRACT400910

Safety, pharmacokinetics (PK), pharmacodynamics ( ... AZD2936 showed an acceptable safety profile and preliminary antitumor activity in pts with advanced/metastatic NSCLC previously treated with standard therapy ...

7. astrazenecaclinicaltrials.com astrazenecaclinicaltrials.com/study/D702BC00001

A Global Phase III Study of Rilvegostomig or ... This is a Phase III, two-arm, randomized, double-blind, global, multicenter study assessing the efficacy and safety of rilvegostomig compared to pembrolizumab.