Dato-DXd + Pembrolizumab for Lung Cancer

Not currently recruiting at 28 trial locations

Overseen By (US & EU sites) Daiichi Sankyo Contact for Clinical Trial Information

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Daiichi Sankyo

Must not be taking: Corticosteroids, Immunosuppressants

Disqualifiers: Autoimmune disease, Organ transplant, CNS metastases, others

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

Compensation: Varies

Number of Visits: 1

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment for individuals with advanced or metastatic non-small cell lung cancer (NSCLC). Researchers aim to determine if the combination of two drugs, datopotamab deruxtecan (a TROP2-directed antibody-drug conjugate) and pembrolizumab, is safe and effective, possibly with added chemotherapy. The trial seeks participants whose lung cancer has progressed despite previous treatments and who have specific types of lung cancer without certain genetic changes. Eligible participants should have experienced a worsening of their condition and not be candidates for curative surgery. 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 treatment.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot use chronic systemic corticosteroids or other immunosuppressive medications during the trial, except for managing side effects.

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

Research shows that using datopotamab deruxtecan (Dato-DXd) with pembrolizumab holds promise for treating advanced non-small cell lung cancer. Studies indicate that most patients tolerate this treatment well. While some side effects can occur, they are usually manageable. Datopotamab deruxtecan has been tested in several studies, demonstrating positive effects against tumors and a safety profile that supports its use in clinical trials. Pembrolizumab is already approved for treating various cancers, so its safety is well-known. As researchers continue to study this combination, they carefully monitor for any side effects to ensure patient safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Datopotamab Deruxtecan (Dato-DXd) combined with Pembrolizumab for lung cancer because it offers a novel approach to tackling the disease. Unlike standard treatments that typically focus on targeting specific proteins like EGFR or ALK, Dato-DXd is an antibody-drug conjugate that delivers a potent chemotherapy directly to cancer cells, potentially minimizing damage to healthy cells. This targeted delivery method could lead to more effective treatment outcomes and fewer side effects. Additionally, when paired with Pembrolizumab, an immunotherapy known for unleashing the immune system against cancer cells, the combination holds promise for enhanced effectiveness in treating advanced or metastatic non-small cell lung cancer (NSCLC).

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

Research has shown that datopotamab deruxtecan (Dato-DXd), which participants in this trial may receive, may effectively treat advanced non-small cell lung cancer (NSCLC). In earlier studies, Dato-DXd helped patients live longer without their cancer worsening compared to the chemotherapy drug docetaxel. This trial tests Dato-DXd in combination with pembrolizumab, another treatment option in this trial and a common treatment for this type of lung cancer. Pembrolizumab alone works well for lung cancer with certain tumor markers. The combination of Dato-DXd and pembrolizumab aims to enhance the overall treatment effect, potentially leading to better results for patients. ^{3 6 7 8 9}

Who Is on the Research Team?

Global Clinical Leader

Principal Investigator

Daiichi Sankyo

Are You a Good Fit for This Trial?

This trial is for adults with advanced or metastatic non-small cell lung cancer (NSCLC) who can't have surgery or chemoradiation. They must have progressed after recent treatment, be able to provide a tumor biopsy, and not have certain genetic alterations in their cancer cells. People with prior severe immune-related side effects from similar drugs, active autoimmune diseases, interstitial lung disease/pneumonitis, other cancers within the last 3 years (with some exceptions), CNS metastases requiring steroids/anticonvulsants are excluded.

Inclusion Criteria

I meet the treatment requirements for advanced lung cancer.

I can provide tissue samples from my initial cancer diagnosis for testing.

My tumor has a KRAS mutation.

Exclusion Criteria

I have not received a live vaccine in the last 30 days.

I am not on long-term steroids or immunosuppressants, except for side effect management.

I have an autoimmune disease.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive datopotamab deruxtecan (Dato-DXd) in combination with pembrolizumab with or without platinum chemotherapy

12 weeks

Cycles 1-4, each cycle is 21 days

Dose Escalation

Dose escalation from 4.0 mg/kg to 6.0 mg/kg of Dato-DXd in combination with pembrolizumab

6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Carboplatin
• Cisplatin
• Datopotamab Deruxtecan
• Pembrolizumab

Trial Overview The study tests Datopotamab Deruxtecan (Dato-DXd) combined with Pembrolizumab and possibly platinum chemotherapy (Carboplatin or Cisplatin). It aims to evaluate the safety and effectiveness of this combination therapy in treating NSCLC that has spread beyond its original site.

How Is the Trial Designed?

Group I: Datopotamab deruxtecan (Dato-DXd) Experimental Treatment 4 Interventions

Dose Escalation and Dose Expansion: Datopotamab deruxtecan (Dato-DXd) in combination with pembrolizumab with or without platinum chemotherapy in participants with advanced or metastatic NSCLC

Who Is Running the Clinical Trial?

Daiichi Sankyo

Lead 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

Daiichi Sankyo, Inc.

Lead Sponsor

Trials

390

Recruited

442,000+

Yuki Abe

Daiichi Sankyo, Inc.

Chief Medical Officer since 2022

MD

Hiroyuki Okuzawa

Daiichi Sankyo, Inc.

Chief Executive Officer

Degree in Social Sciences from Hitotsubashi University

AstraZeneca

Industry 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

Merck Sharp & Dohme LLC

Industry Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Published Research Related to This Trial

The TROPION-Lung08 phase III study is investigating the combination of datopotamab deruxtecan (Dato-DXd) and pembrolizumab as a first-line treatment for patients with advanced non-small-cell lung cancer (NSCLC) who have high PD-L1 expression and no actionable genomic alterations, aiming to improve long-term disease control compared to pembrolizumab alone.

Primary endpoints of the study include progression-free survival and overall survival, with secondary endpoints assessing response rates and safety, indicating a comprehensive evaluation of the new treatment's efficacy and safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

TROPION-Lung08: phase III study of datopotamab deruxtecan plus pembrolizumab as first-line therapy for advanced NSCLC. Levy, BP., Felip, E., Reck, M., et al.[2023]

Pembrolizumab, a monoclonal antibody targeting PD-1, showed significant efficacy in treating a 79-year-old patient with advanced squamous cell lung cancer, leading to a complete response after just 3 cycles of treatment.

However, the patient developed acute myelomonocytic leukemia after starting pembrolizumab, highlighting a potential safety concern that warrants further investigation into the drug's effects on blood cell production.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute myelomonocytic leukemia during pembrolizumab treatment for non-small cell lung cancer: A case report. Kim, HB., Park, SG., Hong, R., et al.[2020]

In a study of 226 gastric adenocarcinoma patients, the 22C3 and 28-8 pharmDx assays showed strong concordance in measuring programmed death ligand-1 (PD-L1) expression, indicating they may be interchangeable for assessing PD-L1 levels.

The 22C3 assay identified a higher rate of PD-L1 positivity (28%) compared to the 28-8 assay (20%), but both assays correlated with tumor characteristics such as mismatch repair proteins and Epstein-Barr virus status, suggesting their relevance in treatment decisions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PD-L1 immunohistochemistry comparison of 22C3 and 28-8 assays for gastric cancer. Narita, Y., Sasaki, E., Masuishi, T., et al.[2022]

Pembrolizumab (Keytruda) is an effective anti-PD1 therapy that has shown overall response rates (ORRs) of 21-34% in melanoma and 19-25% in non-small cell lung cancer (NSCLC), leading to its FDA approval for these cancers.

While pembrolizumab can cause adverse events in up to 60% of patients, serious grade 3/4 toxicities are rare (<10%), although immune-related side effects like thyroid dysfunction and pneumonitis can be severe and may require stopping treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab (Keytruda). Kwok, G., Yau, TC., Chiu, JW., et al.[2023]

Pembrolizumab is an effective treatment for advanced gastric cancer (AGC) in patients who have already undergone two courses of chemotherapy, showing durable responses and an acceptable safety profile.

Approved by the FDA in 2017 for patients with PD-L1 positive AGC, pembrolizumab is now being studied in combination with other treatments, indicating its potential for broader applications in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of pembrolizumab in recurrent or advanced gastric cancer expressing PD-L1 refractory to platinum and fluoropyrimidine. Mishima, S., Kawazoe, A., Shitara, K.[2022]

In the KEYNOTE-189 study, patients with non-squamous non-small cell lung cancer who received the combination of pembrolizumab, pemetrexed, and platinum had a median progression-free survival (PFS) of 9.3 months, significantly longer than the 6.6 months observed in the placebo group, indicating enhanced efficacy of the treatment.

The objective response rate was also higher in the pembrolizumab group (58.7%) compared to the placebo group (28.9%), while the incidence of severe treatment-emergent adverse events (grade ≥3) was similar across both treatment arms, suggesting a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pemetrexed maintenance with or without pembrolizumab in non-squamous non-small cell lung cancer: A cross-trial comparison of KEYNOTE-189 versus PARAMOUNT, PRONOUNCE, and JVBL. Garon, EB., Kim, JS., Govindan, R.[2021]

In a phase I study involving 113 patients with advanced solid tumors, MK-4166 was found to be tolerable, with only 8% of patients experiencing treatment-related grade ≥3 adverse events and no treatment-related deaths reported.

The combination of MK-4166 with pembrolizumab showed promising efficacy, particularly in patients with immune checkpoint inhibitor (ICI)-naïve melanoma, achieving an objective response rate of 62%, indicating potential for effective treatment in this subgroup.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I Study of MK-4166, an Anti-human Glucocorticoid-Induced TNF Receptor Antibody, Alone or with Pembrolizumab in Advanced Solid Tumors. Papadopoulos, KP., Autio, K., Golan, T., et al.[2022]

Pembrolizumab, a PD-1 inhibitor used in cancer treatment, can lead to rare but serious immune-related adverse events, including type 1 diabetes mellitus, occurring in about 0.2% of cases.

A review of 42 cases revealed that patients may develop diabetic ketoacidosis during treatment, highlighting the need for blood glucose monitoring and awareness of this potential side effect among clinicians.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Programmed Cell Death-1 Inhibitor-Induced Type 1 Diabetes Mellitus. Clotman, K., Janssens, K., Specenier, P., et al.[2022]

In a phase II trial involving 15 patients with resectable non-small cell lung cancer (NSCLC), neoadjuvant treatment with pembrolizumab showed a major pathologic response in 27% of patients, indicating promising antitumor activity before surgery.

The treatment was found to be feasible and safe, with only 33% of patients experiencing moderate adverse events, and no postoperative mortality, suggesting that pembrolizumab does not compromise surgical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. Eichhorn, F., Klotz, LV., Kriegsmann, M., et al.[2022]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO-24-01544

Datopotamab Deruxtecan Versus Docetaxel for Previously ... Dato-DXd significantly improved PFS versus docetaxel in patients with advanced/metastatic NSCLC, driven by patients with nonsquamous histology.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05555732

NCT05555732 | Datopotamab Deruxtecan (Dato-DXd) and ... This study is designed to assess the efficacy and safety of datopotamab deruxtecan (Dato-DXd) in combination with pembrolizumab versus pembrolizumab in ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37249038/

TROPION-Lung08: phase III study of datopotamab ... Pembrolizumab monotherapy is a standard first-line treatment for PD-L1-high advanced non-small-cell lung cancer (NSCLC) without actionable ...

4. onclive.com onclive.com/view/datopotamab-deruxtecan-plus-pembrolizumab-displays-efficacy-in-advanced-nsclc-with-or-without-chemotherapy

Datopotamab Deruxtecan Plus Pembrolizumab Displays ... Datopotamab deruxtecan has already shown efficacy NSCLC as a single agent and a phase 3 study [TROPION-Lung01] is ongoing in the second-line ...

5. tandfonline.com tandfonline.com/doi/full/10.2217/fon-2023-0230

TROPION-Lung08: phase III study of datopotamab ... Five-year outcomes with pembrolizumab versus chemotherapy as first-line therapy in patients with non-small-cell lung cancer and programmed death ligand-1 tumor ...

6. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.8501

TROPION-Lung02: Datopotamab deruxtecan (Dato-DXd) ... The combination of Dato-DXd plus pembro treatment both with and without Pt-CT elicited durable antitumor activity in pts with aNSCLC.

7. astrazeneca-us.com astrazeneca-us.com/media/press-releases/2025/DATROWAY-datopotamab-deruxtecan-dlnk-demonstrated-an-unprecedented-median-overall-survival-improvement-of-five-months-vs-chemotherapy-as-1st-line-treatment-for-patients-with-metastatic-triple-negative-breast-cancer-for-whom-immunotherapy-was-not-an-option-in-TROPION-Breast02.html

DATROWAY® (datopotamab deruxtecan-dlnk) ... AstraZeneca and Daiichi Sankyo's DATROWAY also demonstrated a highly statistically significant and clinically meaningful 43% reduction in ...

8. daiichisankyo.us daiichisankyo.us/press-releases/-/article/three-phase-3-trials-of-datopotamab-deruxtecan-based-combinations-initiated-in-patients-with-advanced-nonsquamous-non-small-cell-lung-cancer

Three Phase 3 Trials of Datopotamab Deruxtecan-Based ... The first patients have been dosed in three global, randomized phase 3 trials evaluating the efficacy and safety of datopotamab deruxtecan (Dato- DXd)-based ...

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11572237/

TROPION-Lung07: Phase III study of Dato-DXd + ... Datopotamab deruxtecan (Dato-DXd), a TROP2-directed antibody-drug conjugate, has demonstrated encouraging antitumor activity and safety in this ...