Datopotamab Deruxtecan (Dato-DXd) in Combination With Pembrolizumab With or Without Platinum Chemotherapy in Subjects With Advanced or Metastatic Non-Small Cell Lung Cancer (TROPION-Lung02)

Advanced or Metastatic NSCLC Clinical Trial

Official title:

Phase 1b, Multicenter, Open-label Study of Datopotamab Deruxtecan (Dato-DXd) in Combination With Pembrolizumab With or Without Platinum Chemotherapy in Subjects With Advanced or Metastatic Non-Small Cell Lung Cancer (TROPION-Lung02)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04526691
• Other study ID #: DS1062-A-U102
• Secondary ID: 2020-006047-25jR
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: September 15, 2020
• Est. completion date: June 1, 2025

Study information

• Verified date: February 2024
• Source: Daiichi Sankyo
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

The primary objective of this study will assess safety and treatment activity of datopotamab deruxtecan (Dato-DXd) in combination with pembrolizumab with or without 4 cycles of platinum chemotherapy in participants with advanced or metastatic NSCLC who have either been previously treated or are treatment naïve in a metastatic setting.

Two dose levels of Dato-DXd (4.0 mg/kg and 6.0 mg/kg) will be studied in combination with 200 mg fixed-dose pembrolizumab in 6 study cohorts. This study will be conducted sequentially and dose escalation will occur according to lower dose to higher dose in the same combination regimen (4.0 mg/kg to 6.0 mg/kg) and from 2-drug combination (Dato-DXd and pembrolizumab) to 3-drug combination regimen (Dato-DXd, pembrolizumab, and carboplatin or cisplatin).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 145
• Est. completion date: June 1, 2025
• Est. primary completion date: June 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Histologically confirmed at diagnosis of NSCLC that:

• Is advanced or metastatic.

• Participants with non-squamous histology must have documented negative test results for actionable EGFR and ALK genomic alterations. Participants with squamous histology are required to undergo testing for EGFR and ALK genomic alterations if they are nonsmokers or under the age of 40 years.

• Has either documented negative or unknown test results for actionable genomic alterations in ROS1, NTRK, BRAF, RET, MET, or other actionable oncogenic driver kinases.

• Participants with tumors that harbor KRAS mutations are eligible for this study.

• Participants with non-actionable genomic alterations in EGFR, ALK, ROS1, NTRK, BRAF, RET, MET, or other kinases are eligible for the study.

• Documentation of radiological disease progression while on or after receiving the most recent treatment regimen, if any, for advanced or metastatic NSCLC.

• Must meet the following prior therapy requirements for advanced or metastatic NSCLC:

• Dose escalation (all cohorts): Has received =2 lines of prior anticancer therapy for locally advanced or metastatic NSCLC.

• Dose expansion (cohorts with 4.0 mg/kg or 6.0 mg/kg Dato-DXd in combination with 200 mg fixed dose of pembrolizumab): Has not received PD-1/PD-L1, PD-L2, CTLA-4 directed immunotherapy and may or may not have been treated with systemic chemotherapy for advanced or metastatic NSCLC.

• Dose expansion (cohorts with 4.0 mg/kg or 6.0 mg/kg Dato-DXd in combination with 200 mg fixed dose of pembrolizumab and 4 cycles of AUC 5 carboplatin or cisplatin 75 mg/m^2): Has not been treated with systemic anticancer therapy for advanced or metastatic NSCLC.

• Willing and able to undergo a mandatory tumor biopsy.

• Archival tumor tissue from initial diagnosis, to the extent that archival tumor tissue is available, for measurement of TROP2 expression levels or other biomarkers.

• Has adequate bone marrow reserve and organ function at baseline within 7 days prior to Cycle 1 Day 1.

• Is not a candidate for surgical resection or chemoradiation with curative intent.

Exclusion Criteria:

• Experienced grade 3 or higher immune-related adverse events (AEs) with prior treatment of anti-programmed cell death 1 (anti-PD-1), anti-programmed cell death ligand 1 (anti-PD-L1), or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX 40, CD137).

• Received a live vaccine within 30 days prior to the first dose of study treatment.

• Active, known, or suspected autoimmune disease.

• Concomitant use of chronic systemic (IV or oral) corticosteroids or other immunosuppressive medications, except for managing AEs.

• Prior organ transplantation, including allogeneic tissue or solid organ transplantation.

• Has spinal cord compression or clinically active central nervous system metastases, defined as untreated and symptomatic, or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms.

• History of (non-infectious) interstitial lung disease (ILD)/pneumonitis that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening.

• Clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses.

• History of another primary malignancy (beyond NSCLC) except for:

• Malignancy treated with curative intent and with no known active disease for =3 years.

• Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease.

• Adequately treated carcinoma in situ without evidence of disease.

• Participants with a history of prostate cancer (tumor/node/metastasis stage) of Stage =T2cN0M0 without biochemical recurrence or progression.

Related Conditions & MeSH terms

• Advanced or Metastatic NSCLC
• Carcinoma, Non-Small-Cell Lung

Intervention

Drug:
• Datopotamab deruxtecan
Intravenous infusion every 3 weeks (Q3W) on Day 1 of each 21-day cycle (starting datopotamab deruxtecan dose of 4.0 mg/kg)
• KEYTRUDA®
Intravenous infusion Q3W on Day 1 of each 21-day cycle (fixed pembrolizumab dose 200 mg Q3W)
• Carboplatin
Intravenous infusion Q3W on Day 1 or Day 2 of each 21-day cycle (AUC 5)
• Cisplatin
Intravenous infusion Q3W on Day 1 or Day 2 of each 21-day cycle (75 mg/m^2)

Locations

Country	Name	City	State
Italy	Instituto Europeo Di Oncologica	Milan
Italy	Azienda Ospedaliera San Gerardo	Monza
Italy	Istituto Nazionale Tumori Fondazione G. Pascale di Napoli Struttura di Oncologia	Naples
Japan	National Cancer Center Hospital East	Chiba
Japan	National Cancer Center Hospital	Tokyo
Japan	Showa Univeristy Hospital	Tokyo
Spain	H. Vall Hebrón (Vall Hebron Institut de Oncologia - VHIO)	Barcelona
Spain	(CIOCC-START) Hospital Universitario HM Sanchinarro	Madrid
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	START Madrid - Hospital Universitario Fundacion Jimenez Diaz	Madrid
Spain	Hospital Puerta de Hierro	Majadahonda
Taiwan	Chung Shan Medical University Hospital	Taichung
Taiwan	Taichung Veterans General Hospital	Taichung
Taiwan	National Cheng Kung University Hospital NCKUH	Tainan
Taiwan	National Taiwan University Hospital NTUH	Taipei City
United States	Johns Hopkins Kimmel Cancer Center at Bayview	Baltimore	Maryland
United States	The Skip Viragh Outpatient Cancer Building	Baltimore	Maryland
United States	City of Hope	Duarte	California
United States	Mayo Clinic	Jacksonville	Florida
United States	Mayo Clinic	Rochester	Minnesota
United States	NEXT Oncology	San Antonio	Texas
United States	Quantum Santa Fe	Santa Fe	New Mexico
United States	Mayo Clinic	Scottsdale	Arizona
United States	Johns Hopkins Kimmel Cancer Center	Washington	District of Columbia

Sponsors (3)

Lead Sponsor	Collaborator
Daiichi Sankyo	AstraZeneca, Merck Sharp & Dohme LLC

Countries where clinical trial is conducted

United States,  Italy,  Japan,  Spain,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants with Dose-limiting Toxicities (DLTs) and Treatment-emergent Adverse Events (TEAEs)		Baseline up to Cycle 1 (Days 1 to 21) for DLTs and up to 28 days after last dose for TEAEs, up to approximately 30 months post-dose
Secondary	Objective Response Rate		Baseline up to BOR (confirmed CR or PR), up to approximately 30 months post-dose
Secondary	Duration of Response		From first objective response (confirmed CR or PR) to PD or death (whichever occurs first), up to approximately 30 months post-dose
Secondary	Progression-free Survival		Baseline up PD or death (whichever occurs first), up to approximately 30 months post-dose
Secondary	Overall Survival		Baseline up to death (any cause), up to approximately 30 months post-dose
Secondary	Pharmacokinetic Parameter Maximum Plasma Concentration (Cmax) of Dato-DXd, Total Anti-TROP2 Antibody, and MAAA-1181a		Cycle 1, Day 1: pre-dose, 30 minutes, 3 hours, 5 hours, and 7 hours post-dose; Cycles 1 and 3, Day 2, Day 4, Day 8, and Day 15; Cycles 2-4, Cycle 6, and Cycle 8, Day 1: pre-dose and post-dose (each cycle is 21 days)
Secondary	Pharmacokinetic Parameter Time to Maximum Plasma Concentration (Tmax) of Dato-DXd, Total Anti-TROP2 Antibody, and MAAA-1181a		Cycle 1, Day 1: pre-dose, 30 minutes, 3 hours, 5 hours, and 7 hours post-dose; Cycles 1 and 3, Day 2, Day 4, Day 8, and Day 15; Cycles 2-4, Cycle 6, and Cycle 8, Day 1: pre-dose and post-dose (each cycle is 21 days)
Secondary	Pharmacokinetic Parameter Area Under the Plasma Concentration-Time Curve (AUC) of Dato-DXd, Total Anti-TROP2 Antibody, and MAAA-1181a	Area under the plasma concentration-time curve up to last quantifiable time (AUClast) and area under the plasma concentration-time curve during dosing interval (AUCtau) will be assessed.	Cycle 1, Day 1: pre-dose, 30 minutes, 3 hours, 5 hours, and 7 hours post-dose; Cycles 1 and 3, Day 2, Day 4, Day 8, and Day 15; Cycles 2-4, Cycle 6, and Cycle 8, Day 1: pre-dose and post-dose (each cycle is 21 days)
Secondary	Anti-drug Antibodies for Dato-DXd and Pembrolizumab		Baseline up to approximately 30 months post-dose