Dato-DXd + Pembrolizumab for Lung Cancer

Recruiting at 25 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

145 Participants Needed

Trial Summary

What is the purpose of this trial?

This study will assess safety and treatment activity of datopotamab deruxtecan (Dato-DXd) in combination with pembrolizumab with or without platinum chemotherapy in participants with advanced or metastatic non-small cell lung cancer.

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.

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

The combination of Dato-DXd and pembrolizumab has shown encouraging safety and antitumor activity in advanced non-small-cell lung cancer (NSCLC), as highlighted in the TROPION-Lung08 study. Pembrolizumab alone has demonstrated significant efficacy and long-lasting responses in NSCLC, suggesting potential benefits when combined with Dato-DXd. ^{1 2 3 4 5}

Is the combination of Dato-DXd and Pembrolizumab safe for humans?

The combination of Dato-DXd and Pembrolizumab has shown encouraging safety in advanced non-small-cell lung cancer (NSCLC) patients. Pembrolizumab, used in various cancers, can cause immune-related side effects, including a rare risk of type 1 diabetes in 0.2% of cases. Adverse events have been reported in up to 60% of patients using Pembrolizumab, with serious side effects in some cases. ^{1 2 6 7 8}

What makes the drug Dato-DXd + Pembrolizumab unique for lung cancer?

Dato-DXd + Pembrolizumab is unique because it combines a novel antibody-drug conjugate (Dato-DXd) that targets a specific protein on cancer cells with pembrolizumab, an immunotherapy that helps the immune system attack cancer. This combination aims to improve outcomes for patients with advanced non-small-cell lung cancer who have high levels of a protein called PD-L1, compared to using pembrolizumab alone. ^{1 2 4 5 9}

Research Team

Global Clinical Leader

Principal Investigator

Daiichi Sankyo

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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 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, 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 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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

TROPION-Lung08: phase III study of datopotamab deruxtecan plus pembrolizumab as first-line therapy for advanced NSCLC. [2023]

2. Ireland pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. [2022]

3. United States 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. [2022]

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

Acute myelomonocytic leukemia during pembrolizumab treatment for non-small cell lung cancer: A case report. [2020]

5. China pubmed.ncbi.nlm.nih.gov

PD-L1 immunohistochemistry comparison of 22C3 and 28-8 assays for gastric cancer. [2022]

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

Programmed Cell Death-1 Inhibitor-Induced Type 1 Diabetes Mellitus. [2022]

7. Ireland 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. [2021]

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

Pembrolizumab (Keytruda). [2023]

9. England pubmed.ncbi.nlm.nih.gov

Safety of pembrolizumab in recurrent or advanced gastric cancer expressing PD-L1 refractory to platinum and fluoropyrimidine. [2022]