Clinical trial NCT04526691: 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)
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)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Advanced or Metastatic NSCLC
Keywords: Advanced or Metastatic NSCLC
Datopotamab deruxtecan (Dato-DXd)
Pembrolizumab
KEYNOTE
DS-1062a
Lead sponsor: Daiichi Sankyo
Sponsor class: INDUSTRY
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2020-08-26
Enrollment: 145
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Intervention model description: Dose escalation and dose expansion model
Primary purpose: TREATMENT

Brief 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.

Detailed 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).

Eligibility criteria: 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.

Primary outcomes:
measure: Number of Participants with Dose-limiting Toxicities (DLTs) and Treatment-emergent Adverse Events (TEAEs)
timeFrame: 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 outcomes:
measure: Objective Response Rate
timeFrame: Baseline up to BOR (confirmed CR or PR), up to approximately 30 months post-dose
measure: Duration of Response
timeFrame: From first objective response (confirmed CR or PR) to PD or death (whichever occurs first), up to approximately 30 months post-dose
measure: Progression-free Survival
timeFrame: Baseline up PD or death (whichever occurs first), up to approximately 30 months post-dose
measure: Overall Survival
timeFrame: Baseline up to death (any cause), up to approximately 30 months post-dose
measure: Pharmacokinetic Parameter Maximum Plasma Concentration (Cmax) of Dato-DXd, Total Anti-TROP2 Antibody, and MAAA-1181a
timeFrame: 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)
measure: Pharmacokinetic Parameter Time to Maximum Plasma Concentration (Tmax) of Dato-DXd, Total Anti-TROP2 Antibody, and MAAA-1181a
timeFrame: 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)
measure: Pharmacokinetic Parameter Area Under the Plasma Concentration-Time Curve (AUC) of Dato-DXd, Total Anti-TROP2 Antibody, and MAAA-1181a
timeFrame: 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)
measure: Anti-drug Antibodies for Dato-DXd and Pembrolizumab
timeFrame: Baseline up to approximately 30 months post-dose
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Mayo Clinic
state: Arizona
city: Duarte
country: United States
facility: City of Hope
state: California
city: Washington
country: United States
facility: Johns Hopkins Kimmel Cancer Center
state: District of Columbia
city: Jacksonville
country: United States
facility: Mayo Clinic
state: Florida
city: Baltimore
country: United States
facility: Johns Hopkins Kimmel Cancer Center at Bayview
state: Maryland
city: Baltimore
country: United States
facility: The Skip Viragh Outpatient Cancer Building
state: Maryland
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Santa Fe
country: United States
facility: Quantum Santa Fe
state: New Mexico
city: San Antonio
country: United States
facility: NEXT Oncology
state: Texas
city: Milan
country: Italy
facility: Instituto Europeo Di Oncologica
city: Monza
country: Italy
facility: Azienda Ospedaliera San Gerardo
city: Naples
country: Italy
facility: Istituto Nazionale Tumori Fondazione G. Pascale di Napoli Struttura di Oncologia
city: Chiba
country: Japan
facility: National Cancer Center Hospital East
city: Tokyo
country: Japan
facility: National Cancer Center Hospital
city: Tokyo
country: Japan
facility: Showa Medical University Hospital
city: Barcelona
country: Spain
facility: H. Vall Hebrón (Vall Hebron Institut de Oncologia - VHIO)
city: Madrid
country: Spain
facility: START Madrid - Hospital Universitario Fundacion Jimenez Diaz
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Madrid
country: Spain
facility: (CIOCC-START) Hospital Universitario HM Sanchinarro
city: Majadahonda
country: Spain
facility: Hospital Puerta de Hierro
city: Taichung
country: Taiwan
facility: Chung Shan Medical University Hospital
city: Taichung
country: Taiwan
facility: Taichung Veterans General Hospital
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital NCKUH
city: Taipei City
country: Taiwan
facility: National Taiwan University Hospital NTUH
Study officials:
affiliation: Daiichi Sankyo
name: Global Clinical Leader
role: STUDY_DIRECTOR
References: