Clinical trial • Phase II • Oncology

DATOPOTAMAB DERUXTECAN for Advanced non-small cell lung cancer | Non-small cell lung cancer

Phase II trial of DATOPOTAMAB DERUXTECAN for Advanced non-small cell lung cancer | Non-small cell lung cancer.

Overview

Trial Therapeutic Area
Oncology
Trial Disease
Advanced non-small cell lung cancer | Non-small cell lung cancer
Trial Stage
Phase II
Drug Modality
ADC | Small molecule | Monoclonal antibody
Orphan Drug
Yes

Key dates

Initial CTIS Submission Date
05-07-2024
First CTIS Authorization Date
14-08-2024

Trial design

open-label, none/not specified-controlled, adaptive Phase II trial across 16 sites in Italy, Netherlands, Norway and others.

Open Label
Yes
Comparator
None/Not specified
Adaptive
True, Study is modular in design consisting of biomarker-matched and biomarker non-matched cohorts (biomarker-directed phase 2 platform study).
Biomarker Stratified
True, EGFR mutation status; biomarker-matched and biomarker non-matched cohorts
Target Sample Size
54

Eligibility

Recruits 54 Vulnerable population selected; informed consent is obtained using subject information and informed consent forms. Subject information and informed consent forms for adults, pregnant partners and pre-screening are listed in the application documents (ICFs available in multiple languages). No specific assent/parental consent procedures for minors are described in the record..

Vulnerable Population
Vulnerable population selected; informed consent is obtained using subject information and informed consent forms. Subject information and informed consent forms for adults, pregnant partners and pre-screening are listed in the application documents (ICFs available in multiple languages). No specific assent/parental consent procedures for minors are described in the record.

Inclusion criteria

  • {"criterion_text":"- NSCLC with the following features: (a) Locally advanced or metastatic disease (ie, advanced NSCLC) not amenable to curative surgery or radiotherapy at study entry. (b) Histologically or cytologically confirmed adenocarcinoma of the lung (patients with mixed histology are eligible if adenocarcinoma is the predominant histology) harboring EGFR mutation(s) known to be associated with EGFR TKI sensitivity at diagnosis. (c) Received only one line of therapy, with single-agent osimertinib, for advanced NSCLC, with clinical benefit as judged by investigator discretion. (Note: a ‘line’ of therapy is defined as a daily anti-cancer treatment administered for >14 days, or a single infusion of an intravenous anti-cancer treatment. For instance, patients who have had <14 days of a first- or second- generation TKI prior to osimertinib, and stopped due to adverse events, would be eligible to enter this study, see also exclusion criteria 5). Patients previously treated adjuvantly or neo-adjuvantly are eligible per exclusion criterion 5. (d) Evidence of radiological disease progression on first-line monotherapy with osimertinib 80 mg po QD."}
  • {"criterion_text":"- Suitable for a mandatory biopsy defined as having an accessible tumor; by whichever modality the site uses and, ideally, confirmed by the person who will perform the procedure; and a stable clinical condition that will allow the patient to tolerate the procedure. The biopsy should be performed within 60 days of the planned first dose of study treatment."}
  • {"criterion_text":"- Patients must have measurable disease per RECIST 1.1, as defined by at least 1 lesion that can be accurately measured at baseline as ≥ 10 mm at the longest diameter (except lymph nodes which must have a short axis ≥ 15 mm) with computed tomography (CT) or magnetic resonance imaging (MRI), which is suitable for accurate repeated measurements. Previously irradiated lesions or a lesion in the field of radiation should not be used as measurable disease unless the lesion(s) has/have demonstrated unequivocal disease progression by RECIST 1.1. Target lesions should not be used for the baseline tumour biopsy, unless there are no other lesions suitable for biopsy and they fulfil requirements."}
  • {"criterion_text":"- Adequate coagulation parameters, defined as: International Normalisation Ratio (INR) < 1.5 × upper limit of normal (ULN) and activated partial thromboplastin time < 1.5 × ULN unless patients are receiving therapeutic anti-coagulation which affects these parameters."}

Exclusion criteria

  • {"criterion_text":"- Patients whose disease has progressed within the first 3 months of osimertinib treatment (refractory to osimertinib treatment)."}
  • {"criterion_text":"- Patients must not have experienced a toxicity(-ies) that led to permanent discontinuation or dose reduction of prior osimertinib. (a) Patients who had dose reductions in the past, but were receiving a full dose of osimertinib at the time of pre-screening should be discussed with the Study Physician."}
  • {"criterion_text":"- Any unresolved toxicities from prior osimertinib treatment greater than CTCAE Grade 1 at the time of starting study treatment."}
  • {"criterion_text":"- Patients should not have discontinued osimertinib >60 days prior to the first dose of study treatment."}
  • {"criterion_text":"- Inadequate bone marrow reserve or organ function as demonstrated by any of the following laboratory values: a) Absolute neutrophil count < 1.5 × 109/L. b) Platelet count < 100 × 109/L. c) Haemoglobin < 9 g/dL. d) Alanine transaminase (ALT) > 2.5 × ULN. e) Aspartate aminotransferase (AST) > 2.5 × ULN. f) Total bilirubin (TBL) > 1.5 × ULN, or > 3 × ULN in the presence of documented Gilbert’s Syndrome (unconjugated hyperbilirubinaemia)."}
  • {"criterion_text":"- Creatinine clearance (CrCl) < 50 mL/min, calculated using Cockcroft-Gault equation (Cockcroft and Gault 1976) or 24-hour urine collection."}

Endpoints

Primary endpoints

  • {"endpoint_text":"- To assess the efficacy of each treatment by evaluation of objective response rate - Endpoint based on Response Evaluation Criteria in Solid Tumours (RECIST 1.1) • Objective response rate (ORR)","definition_or_measurement_approach":"Endpoint based on Response Evaluation Criteria in Solid Tumours (RECIST 1.1); Objective response rate (ORR)"}

Secondary endpoints

  • {"endpoint_text":"- To assess the efficacy of each treatment by evaluation of tumour response and overall survival Overall survival (OS) - Endpoint based on Response Evaluation Criteria in Solid Tumours (RECIST 1.1): • Progression-free survival (PFS) • Duration of response (DoR)","definition_or_measurement_approach":"Tumour response and survival endpoints measured using RECIST 1.1; includes Progression-free survival (PFS), Duration of response (DoR) and Overall survival (OS)."}
  • {"endpoint_text":"- To assess the pharmacokinetics (PK) of each treatment: plasma/serum concentrations will be measured.","definition_or_measurement_approach":"PK endpoints: plasma/serum concentrations of specific agents measured at selected time points."}
  • {"endpoint_text":"- To assess the safety and tolerability of each treatment - • Adverse events/serious adverse events (AEs/SAEs): • Physical examinations • Laboratory findings • Vital signs • Electrocardiogram (ECG). • Left ventricular ejection fraction (LVEF)","definition_or_measurement_approach":"Safety/tolerability assessed via AEs/SAEs reporting, physical examinations, laboratory tests, vital signs, ECG and LVEF measurements."}

Recruitment

Planned Sample Size
54
Recruitment Window Months
10
Consent Approach
Informed consent obtained using subject information and informed consent forms (L1_SIS and ICF documents). ICFs available for adults and for specific modules; documents listed in multiple languages including Italian, Dutch, Spanish, Swedish, Norwegian and English. No specific information on assent or parental consent for minors is provided in the record.

Geography

Total Number Of Sites
16
Total Number Of Participants
45

Italy

Earliest CTIS Part Ii Submission Date
20-08-2024
Latest Decision Or Authorization Date
09-12-2024
Processing Time Days
111
Number Of Sites
3
Number Of Participants
15

Sites

Site Name
Istituto Oncologico Veneto
Department Name
Oncology 2
Principal Investigator Name
Laura Bonanno
Principal Investigator Email
laura.bonanno@iov.veneto.it
Contact Person Name
Laura Bonanno
Contact Person Email
laura.bonanno@iov.veneto.it
Site Name
Azienda Ospedaliero-Universitaria San Luigi Gonzaga
Department Name
Oncologia
Principal Investigator Name
Silvia Novello
Principal Investigator Email
silvia.novello@unito.it
Contact Person Name
Silvia Novello
Contact Person Email
silvia.novello@unito.it
Site Name
IRCCS Istituto Nazionale Tumori Fondazione Pascale
Department Name
S.C. Oncologia Clinica Sperimentale Toraco-Polmonare
Principal Investigator Name
Alessandro Morabito
Principal Investigator Email
a.morabito@istitutotumori.na.it
Contact Person Name
Alessandro Morabito

Netherlands

Earliest CTIS Part Ii Submission Date
14-08-2024
Latest Decision Or Authorization Date
17-01-2025
Processing Time Days
156
Number Of Sites
4
Number Of Participants
13

Sites

Site Name
Academisch Ziekenhuis Maastricht
Department Name
longziekten
Principal Investigator Name
Lizza Hendriks
Principal Investigator Email
lizza.hendriks@mumc.nl
Contact Person Name
Lizza Hendriks
Contact Person Email
lizza.hendriks@mumc.nl
Site Name
Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)
Department Name
Afdeling Oncologie
Principal Investigator Name
Marthe Paats
Principal Investigator Email
m.paats@erasmusmc.nl
Contact Person Name
Marthe Paats
Contact Person Email
m.paats@erasmusmc.nl
Site Name
Stichting Amsterdam UMC
Department Name
Afdeling Medische Oncologie
Principal Investigator Name
Sayed Hashemi
Principal Investigator Email
s.hashemi@vumc.nl
Contact Person Name
Sayed Hashemi
Contact Person Email
s.hashemi@vumc.nl
Site Name
Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis Stichting
Department Name
Thoraxoncologie
Principal Investigator Name
Adrianus Johannes de Langen
Principal Investigator Email
j.d.langen@nki.nl
Contact Person Name
Adrianus Johannes de Langen
Contact Person Email
j.d.langen@nki.nl

Norway

Earliest CTIS Part Ii Submission Date
15-08-2024
Latest Decision Or Authorization Date
20-12-2024
Processing Time Days
127
Number Of Sites
3
Number Of Participants
8

Sites

Site Name
St. Olavs Hospital HF
Department Name
Onkologisk avdeling
Principal Investigator Name
Bjørn Grønberg
Principal Investigator Email
Bjorn.Gronberg@stolav.no
Contact Person Name
Bjørn Grønberg
Contact Person Email
Bjorn.Gronberg@stolav.no
Site Name
Oslo University Hospital HF
Department Name
Onkologisk avdeling
Principal Investigator Name
Knut Smeland
Principal Investigator Email
knusme@ous-hf.no
Contact Person Name
Knut Smeland
Contact Person Email
knusme@ous-hf.no
Site Name
Vestre Viken HF
Department Name
Onkologisk avdeling
Principal Investigator Name
Odd Terje Brustugun
Principal Investigator Email
OTR@vestreviken.no
Contact Person Name
Odd Terje Brustugun
Contact Person Email
OTR@vestreviken.no

Sweden

Earliest CTIS Part Ii Submission Date
14-08-2024
Latest Decision Or Authorization Date
05-12-2024
Processing Time Days
113
Number Of Sites
1
Number Of Participants
2

Sites

Site Name
Karolinska University Hospital
Department Name
Cancerstudieenheten
Principal Investigator Name
Simon Ekman
Principal Investigator Email
simon.ekman@ki.se
Contact Person Name
Simon Ekman
Contact Person Email
simon.ekman@ki.se

Spain

Earliest CTIS Part Ii Submission Date
14-08-2024
Latest Decision Or Authorization Date
05-12-2024
Processing Time Days
113
Number Of Sites
5
Number Of Participants
7

Sites

Site Name
Hospital Universitario La Paz
Department Name
Oncología
Principal Investigator Name
Javier de Castro
Principal Investigator Email
javier.decastro@salud.madrid.org
Contact Person Name
Javier de Castro
Site Name
Complexo Hospitalario Universitario A Coruna
Department Name
Oncología
Principal Investigator Name
Rosario García Campelo
Principal Investigator Email
MA.Rosario.Garcia.Campelo@sergas.es
Contact Person Name
Rosario García Campelo
Site Name
Hospital Universitario 12 De Octubre
Department Name
Oncología
Principal Investigator Name
Santiago Ponce
Principal Investigator Email
sponceaix@gmail.com
Contact Person Name
Santiago Ponce
Contact Person Email
sponceaix@gmail.com
Site Name
Hospital Clinic De Barcelona
Department Name
Oncología
Principal Investigator Name
Noemí Reguart
Principal Investigator Email
nreguart@clinic.cat
Contact Person Name
Noemí Reguart
Contact Person Email
nreguart@clinic.cat
Site Name
Hospital De La Santa Creu I Sant Pau
Department Name
Oncología
Principal Investigator Name
Margarita Majem
Principal Investigator Email
mmajem@santpau.cat
Contact Person Name
Margarita Majem
Contact Person Email
mmajem@santpau.cat

Sponsor

Primary sponsor

Full Name
AstraZeneca AB
Organisation Type
Pharmaceutical company
Country Of Registered Address
Sweden

Investigational products

Investigational Product Name
Datopotamab deruxtecan
Active Substance
DATOPOTAMAB DERUXTECAN
Modality
ADC
Routes Of Administration
INFUSION
Route
INFUSION
Authorisation Status
PRD9684738
Maximum Dose
6 mg/Kg (max daily dose amount 6 mg/Kg as listed)
Investigational Product Name
TAGRISSO 80 mg film-coated tablets
Active Substance
OSIMERTINIB
Modality
Small molecule
Routes Of Administration
ORAL USE
Route
ORAL
Authorisation Status
EU/1/16/1086/004
Starting Dose
80 mg po QD
Frequency
Once daily (QD) as per product description/inclusion criteria
Maximum Dose
80 mg
Investigational Product Name
TAGRISSO 40 mg film-coated tablets
Active Substance
OSIMERTINIB
Modality
Small molecule
Routes Of Administration
ORAL USE
Route
ORAL
Authorisation Status
EU/1/16/1086/003
Maximum Dose
80 mg (product max daily dose listed 80 mg)
Investigational Product Name
Koselugo 25 mg hard capsules
Active Substance
SELUMETINIB
Modality
Small molecule
Routes Of Administration
ORAL USE
Route
ORAL
Authorisation Status
EU/1/21/1552/002
Orphan Designation
Yes
Maximum Dose
150 mg
Investigational Product Name
IMFINZI 50 mg/mL concentrate for solution for infusion.
Active Substance
DURVALUMAB
Modality
Monoclonal antibody
Routes Of Administration
IV INFUSION
Route
IV INFUSION
Authorisation Status
EU/1/18/1322/001
Maximum Dose
1500 mg/m2 (max daily dose amount listed 1500 mg/m2)
Investigational Product Name
CISPLATIN
Active Substance
CISPLATIN
Modality
Small molecule
Routes Of Administration
IV INFUSION
Route
IV INFUSION
Authorisation Status
SUB07483MIG
Maximum Dose
80 mg/m2 (max daily dose amount listed 80 mg/m2; max total dose amount 300 mg)
Investigational Product Name
ETOPOSIDE
Active Substance
ETOPOSIDE
Modality
Small molecule
Routes Of Administration
IV INFUSION
Route
IV INFUSION
Authorisation Status
SUB07337MIG
Maximum Dose
100 mg/m2
Investigational Product Name
CARBOPLATIN
Active Substance
CARBOPLATIN
Modality
Small molecule
Routes Of Administration
INTRAVENIOUS INFUSION
Route
INTRAVENIOUS INFUSION
Authorisation Status
SUB06614MIG
Maximum Dose
750 mg/m2
Investigational Product Name
Inflectra 100 mg powder for concentrate for solution for infusion
Active Substance
INFLIXIMAB
Modality
Monoclonal antibody
Routes Of Administration
ORAL
Route
ORAL
Authorisation Status
EU/1/13/854 (multiple PRD numbers listed)
Investigational Product Name
Mycophenolate Mofetil Accord 250 mg capsules
Active Substance
MYCOPHENOLATE MOFETIL
Modality
Small molecule
Routes Of Administration
ORAL
Route
ORAL
Authorisation Status
PA 2315/064/001
Combination Treatment
Yes

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