Dato-DXd + Rilvegostomig for Lung Cancer

(TROPION-Lung12 Trial)

Recruiting at 212 trial locations

Overseen By AstraZeneca Clinical Study Information Center

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: AstraZeneca

Disqualifiers: EGFR mutation, ALK alteration, ILD, others

Stay on Your Current Meds You can continue your current medications while participating

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 16

Duration: 48 weeks

660 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the effectiveness of a new drug combination for individuals with early-stage lung cancer, specifically adenocarcinoma NSCLC. The trial compares two drugs, Datopotamab Deruxtecan (Dato-DXd) and rilvegostomig, against the usual care, which may include chemotherapy or observation. It targets individuals who have undergone surgical removal of lung cancer but still possess certain risk factors, such as specific DNA markers (ctDNA-positive) or high-risk cancer features. This trial may suit those who recently had lung cancer surgery and meet the specific risk criteria. As a Phase 3 trial, it represents the final step before FDA approval, offering participants the opportunity to contribute to potentially groundbreaking treatment advancements.

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.

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

Research shows that the combination of Dato-DXd and rilvegostomig is generally safe. The safety profile of this combination aligns with what is known about each drug individually. In previous studies, patients tolerated the treatment well, with no unexpected side effects. Specifically, studies found rilvegostomig alone to be safe for patients with lung cancer, demonstrating good tolerance and a strong safety record. Overall, earlier research has shown both treatments to be safe, which is encouraging for their use in this trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they offer a fresh approach to tackling lung cancer. Unlike the standard chemotherapy options, Datopotamab Deruxtecan (Dato-DXd) is an antibody-drug conjugate, which means it combines a targeted antibody with a chemotherapy drug, aiming directly at cancer cells with precision. Rilvegostomig, another investigational treatment in the trial, is a novel agent delivered via intravenous infusion, designed to work in synergy with Dato-DXd or as a standalone therapy to enhance efficacy. This targeted approach could potentially minimize side effects compared to traditional chemotherapy, making it a promising alternative for patients.

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

Research has shown that the combination of datopotamab deruxtecan (Dato-DXd) and rilvegostomig, which participants in one arm of this trial may receive, yields promising results in treating certain cancers. Dato-DXd targets a protein called TROP2, often found in large amounts on cancer cells, and effectively delivers treatment to these cells. In earlier studies, this combination demonstrated strong cancer-fighting activity and was well-tolerated by patients with advanced bladder cancer.

Rilvegostomig alone, another treatment arm in this trial, has also shown positive effects in treating non-small cell lung cancer (NSCLC). Early studies reported it as safe and effective, especially for patients who haven't had certain previous treatments. Together, these findings offer hope for using Dato-DXd and rilvegostomig in treating lung cancer. ^{2 4 5 6 7}

Who Is on the 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

Are You a Good Fit for This Trial?

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 surgery showed no signs of cancer remaining.

My bone marrow and organs are functioning well.

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Datopotamab Deruxtecan
• Rilvegostomig

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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) 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]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/34413126/

Datopotamab Deruxtecan, a Novel TROP2-directed ... Dato-DXd demonstrated potent antitumor activity against TROP2-expressing tumors by efficient payload delivery into tumors and acceptable safety profiles in ...

2. daiichisankyo.us daiichisankyo.us/press-releases/-/article/datroway-plus-rilvegostomig-showed-promising-tumor-responses-in-patients-with-metastatic-urothelial-cancer-in-tropion-pantumor03-phase-2-trial

DATROWAY Plus Rilvegostomig Showed Promising Tumor ... DATROWAY Plus Rilvegostomig Showed Promising Tumor Responses in Patients with Metastatic Urothelial Cancer in TROPION-PanTumor03 Phase 2 Trial.

3. onclive.com onclive.com/view/dato-dxd-plus-rilvegostomig-elicits-activity-in-cisplatin-ineligible-or-platinum-pretreated-urothelial-cancer

Dato-DXd Plus Rilvegostomig Elicits Activity in Cisplatin- ... The combination of datopotamab deruxtecan-dlnk (Dato-DXd; Datroway) and rilvegostomig demonstrated potent antitumor activity as first-line ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT05489211

NCT05489211 | Study of Dato-Dxd as Monotherapy and in ... This study will evaluate various solid tumour types, including endometrial cancer (Substudy 1), gastric cancer (Substudy 2), metastatic castration-resistant ...

5. astrazeneca.com astrazeneca.com/content/astraz/media-centre/press-releases/2023/datopotamab-deruxtecan-plus-imfinzi-showed-promising-clinical-activity-in-the-first-line-advanced-non-small-cell-lung-cancer-setting.html

Datopotamab deruxtecan plus Imfinzi showed promising ... AstraZeneca and Daiichi Sankyo's datopotamab deruxtecan plus Imfinzi with or without chemotherapy demonstrated objective response rates of 77% and 50%.

6. datasourcebydaiichisankyo.com datasourcebydaiichisankyo.com/documents/d/datahub/asco-2025_dato-dxd_waqar_poster_final

First-line datopotamab deruxtecan (Dato-DXd) + ... The safety profile for the combination of Dato-DXd and rilvegostomig was consistent with the known safety profiles of each individual agent,.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12034271/

Therapeutic Potential of Datopotamab Deruxtecan in the ... Progress in targeted therapy and immunotherapy has greatly improved outcomes for NSCLC patients, especially those with identifiable genetic ...