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)

Sponsor

Daiichi Sankyo, Inc. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04526691

Collaborator

AstraZeneca (Industry), Merck Sharp & Dohme LLC (Industry)

120

Enrollment

Locations

Arm

48.5

Anticipated Duration (Months)

4.8

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Advanced or Metastatic NSCLC	Drug: Datopotamab deruxtecan Drug: Pembrolizumab Drug: Carboplatin Drug: Cisplatin	Phase 1

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).

Study Design

Study Type:

Interventional

Anticipated Enrollment :

120 participants

Allocation:

N/A

Intervention Model:

Sequential Assignment

Intervention Model Description:

Dose escalation and dose expansion modelDose escalation and dose expansion model

Masking:

None (Open Label)

Primary Purpose:

Treatment

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)

Actual Study Start Date :

Sep 15, 2020

Anticipated Primary Completion Date :

Dec 15, 2022

Anticipated Study Completion Date :

Oct 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Datopotamab deruxtecan (Dato-DXd) 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	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) Other Names: Dato-DXd Drug: Pembrolizumab Intravenous infusion Q3W on Day 1 of each 21-day cycle (fixed pembrolizumab dose 200 mg Q3W) Drug: Carboplatin Intravenous infusion Q3W on Day 1 or Day 2 of each 21-day cycle (AUC 5) Drug: Cisplatin Intravenous infusion Q3W on Day 1 or Day 2 of each 21-day cycle (75 mg/m^2)

Arm

Intervention/Treatment

Experimental: Datopotamab deruxtecan (Dato-DXd)

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

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)

Other Names:

Dato-DXd

Drug: Pembrolizumab

Intravenous infusion Q3W on Day 1 of each 21-day cycle (fixed pembrolizumab dose 200 mg Q3W)

Drug: Carboplatin

Intravenous infusion Q3W on Day 1 or Day 2 of each 21-day cycle (AUC 5)

Drug: Cisplatin

Intravenous infusion Q3W on Day 1 or Day 2 of each 21-day cycle (75 mg/m^2)

Outcome Measures

Primary Outcome Measures

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 Outcome Measures

Objective Response Rate [Baseline up to BOR (confirmed CR or PR), up to approximately 30 months post-dose]
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]
Progression-free Survival [Baseline up PD or death (whichever occurs first), up to approximately 30 months post-dose]
Overall Survival [Baseline up to death (any cause), up to approximately 30 months post-dose]
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)]
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)]
Pharmacokinetic Parameter Area Under the Plasma Concentration-Time Curve (AUC) 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)]
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.
Anti-drug Antibodies for Dato-DXd and Pembrolizumab [Baseline up to approximately 30 months post-dose]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic	Scottsdale	Arizona	United States	85259
2	City of Hope	Duarte	California	United States	91010
3	Johns Hopkins Kimmel Cancer Center	Washington	District of Columbia	United States	20016
4	Mayo Clinic	Jacksonville	Florida	United States	32224
5	Johns Hopkins Kimmel Cancer Center at Bayview	Baltimore	Maryland	United States	21224
6	The Skip Viragh Outpatient Cancer Building	Baltimore	Maryland	United States	21287
7	Mayo Clinic	Rochester	Minnesota	United States	55905
8	Quantum Santa Fe	Santa Fe	New Mexico	United States	87505
9	NEXT Oncology	San Antonio	Texas	United States	78229
10	Instituto Europeo Di Oncologica	Milan		Italy	20141
11	Azienda Ospedaliera San Gerardo	Monza		Italy	20052
12	Istituto Nazionale Tumori Fondazione G. Pascale di Napoli Struttura di Oncologia	Naples		Italy	80131
13	Azienda Ospedaliero Universitaria di Parma	Parma		Italy	43126
14	National Cancer Center Hospital East	Chiba		Japan	277-8577
15	National Cancer Center Hospital	Tokyo		Japan	104-0045
16	Showa Univeristy Hospital	Tokyo		Japan	142-8555
17	H. Vall Hebrón (Vall Hebron Institut de Oncologia - VHIO)	Barcelona		Spain	08035
18	START Madrid - Hospital Universitario Fundacion Jimenez Diaz	Madrid		Spain	28040
19	Hospital Universitario 12 de Octubre	Madrid		Spain	28041
20	(CIOCC-START) Hospital Universitario HM Sanchinarro	Madrid		Spain	28050
21	Hospital Puerta de Hierro	Majadahonda		Spain	28222
22	Chung Shan Medical University Hospital	Taichung		Taiwan	40201
23	Taichung Veterans General Hospital	Taichung		Taiwan	40705
24	National Cheng Kung University Hospital NCKUH	Tainan		Taiwan	704
25	National Taiwan University Hospital NTUH	Taipei City		Taiwan	100