Dato-DXd + Rilvegostomig for Lung Cancer

(TROPION-Lung12 Trial)

Recruiting at 169 trial locations

Overseen By AstraZeneca Clinical Study Information Center

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: AstraZeneca

Disqualifiers: EGFR mutation, ALK alteration, ILD, others

Stay on Your Current Meds

No Placebo Group

Pivotal Trial (Near Approval)

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This is a Phase III, randomised, open-label, multicentre, global study assessing the efficacy and safety of adjuvant Dato-DXd in combination with rilvegostomig compared with SoC, after complete surgical resection (R0) in participants with Stage I adenocarcinoma NSCLC who are ctDNA-positive, as determined by the Sponsor-designated ctDNA assay, or have at least one high-risk pathological feature.

Do I need to stop my current medications for the trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the drug Dato-DXd + Rilvegostomig for lung cancer?

Preliminary findings suggest that the drug datopotamab deruxtecan (Dato-DXd), which is part of the treatment, may be effective in patients with advanced non-small cell lung cancer, showing responses in nearly a quarter of patients in a phase I trial. Additionally, antibody-drug conjugates like Dato-DXd have shown promising results in lung cancer, with significant antitumor activity and manageable side effects. ^{1 2 3 4 5}

How is the drug Dato-DXd unique for lung cancer treatment?

Dato-DXd is unique because it is an antibody-drug conjugate (ADC) that targets TROP2, a protein found on cancer cells, and delivers a powerful chemotherapy agent directly to these cells, potentially reducing side effects and improving effectiveness compared to traditional chemotherapy. ^{1 2 3 4 5}

Research Team

Enriqueta Felip

Principal Investigator

Vall d'Hebron Hospital, Barcelona, Spain

David Jones, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center, New York, United States of America

Eligibility Criteria

This trial is for people who've had surgery to remove Stage I adenocarcinoma NSCLC and are either ctDNA-positive or have high-risk features. Participants should not have received prior systemic therapy for their lung cancer.

Inclusion Criteria

My bone marrow and organs are functioning well.

My surgery showed no signs of cancer remaining.

My lung cancer is in an early stage and has not been treated yet.

Exclusion Criteria

My cancer has a specific change in the EGFR gene or ALK gene.

I have a serious eye condition affecting my cornea.

I have or had an autoimmune or inflammatory disorder.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Dato-DXd in combination with rilvegostomig or rilvegostomig monotherapy or Standard of Care, administered as intravenous infusions every 3 weeks

48 weeks

16 visits (in-person, every 3 weeks)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with assessments of disease-free survival and overall survival

Up to approximately 10 years

Long-term Follow-up

Participants' overall survival and quality of life are monitored, with assessments at weeks 12, 24, and 48

Up to approximately 10 years

Treatment Details

Interventions

• Datopotamab Deruxtecan (Anti-tumor antibiotic)
• Rilvegostomig (Other)

Trial Overview The study compares adjuvant Dato-DXd with rilvegostomig versus standard chemotherapy drugs (like Pemetrexed, UFT, Etoposide) after tumor removal in patients with a specific type of lung cancer.

Participant Groups

Group I: Rilvegostomig Experimental Treatment 1 Intervention

Participants in the rilvegostomig monotherapy group will receive rilvegostomig as intravenous (IV) infusion every 3 weeks (Q3W).

Group II: Dato-DXd + rilvegostomig Experimental Treatment 2 Interventions

Participants in the Dato-DXd in combination with rilvegostomig group will receive Dato-DXd and rilvegostomig as intravenous (IV) infusion every 3 weeks (Q3W).

Group III: Standard of Care (SoC) Active Control 6 Interventions

Patients in SoC group will undergo observation or will receive Investigator's Choice of Chemotherapy (ICC).

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

Daiichi Sankyo

Industry Sponsor

Trials

443

Recruited

493,000+

Hiroyuki Okuzawa

Daiichi Sankyo

Chief Executive Officer

Degree in Social Sciences from Hitotsubashi University

Yuki Abe

Daiichi Sankyo

Chief Medical Officer since 2023

MD

Findings from Research

In a phase I trial, the TROP2-directed antibody-drug conjugate datopotamab deruxtecan showed promising activity in patients with advanced or metastatic non-small cell lung cancer, with nearly 25% of participants responding to the treatment.

The treatment was associated with manageable side effects, suggesting it could be a safe option for patients with this type of lung cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

TROP2 ADC Intrigues in NSCLC. [2021]

Datopotamab deruxtecan (Dato-DXd) demonstrated promising antitumor activity in patients with advanced non-small-cell lung cancer (NSCLC), achieving an objective response rate of 26% and a median duration of response of 10.5 months in a study involving 210 patients.

The treatment was generally well-tolerated, with a maximum tolerated dose of 8 mg/kg and a recommended dose of 6 mg/kg, although some patients experienced treatment-emergent adverse events, including nausea and interstitial lung disease, indicating a manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-in-Human, Phase I Dose-Escalation and Dose-Expansion Study of Trophoblast Cell-Surface Antigen 2-Directed Antibody-Drug Conjugate Datopotamab Deruxtecan in Non-Small-Cell Lung Cancer: TROPION-PanTumor01. Shimizu, T., Sands, J., Yoh, K., et al.[2023]

Antibody-drug conjugates (ADCs) are showing promising results in lung cancer treatment, with impressive response rates and survival outcomes in patients who have already undergone other treatments.

Current clinical trials are exploring various ADCs targeting different proteins in lung cancer, and novel strategies are being developed to enhance their safety and efficacy, such as increasing the drug-to-antibody ratio and using more potent payloads.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antibody-drug conjugates: A promising novel therapeutic approach in lung cancer. Desai, A., Abdayem, P., Adjei, AA., et al.[2022]

Antibody Drug Conjugates (ADCs) are a promising new treatment for various cancers, including lung cancer, as they combine an antibody targeting tumor cells with a powerful cytotoxic drug.

Trastuzumab Deruxtecan (T-DXd) is the first ADC approved by the FDA for lung cancer, showing significant effectiveness in tumors with HER2 mutations based on results from the Destiny-Lung01 and Lung02 trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antibody-Drug Conjugates for Lung Cancer: Payloads and Progress. Rosner, S., Valdivia, A., Hoe, HJ., et al.[2023]

Datopotamab deruxtecan (Dato-DXd) is a promising new treatment for patients with metastatic HR+/HER2- breast cancer, particularly for those who have limited options after endocrine therapy and chemotherapy.

The ongoing phase III TROPION-Breast01 study is comparing the efficacy and safety of Dato-DXd against standard chemotherapy in patients who have already received one or two lines of systemic treatment, aiming to improve outcomes in this challenging patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

TROPION-Breast01: Datopotamab deruxtecan vs chemotherapy in pre-treated inoperable or metastatic HR+/HER2- breast cancer. Bardia, A., Jhaveri, K., Kalinsky, K., et al.[2023]

References

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

TROP2 ADC Intrigues in NSCLC. [2021]

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

First-in-Human, Phase I Dose-Escalation and Dose-Expansion Study of Trophoblast Cell-Surface Antigen 2-Directed Antibody-Drug Conjugate Datopotamab Deruxtecan in Non-Small-Cell Lung Cancer: TROPION-PanTumor01. [2023]

3. Ireland pubmed.ncbi.nlm.nih.gov

Antibody-drug conjugates: A promising novel therapeutic approach in lung cancer. [2022]

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

Antibody-Drug Conjugates for Lung Cancer: Payloads and Progress. [2023]

5. England pubmed.ncbi.nlm.nih.gov

TROPION-Breast01: Datopotamab deruxtecan vs chemotherapy in pre-treated inoperable or metastatic HR+/HER2- breast cancer. [2023]