Clinical Trials Register

Summary
EudraCT Number:	2016-002579-83
Sponsor's Protocol Code Number:	54767414LUC2001
National Competent Authority:	Hungary - National Institute of Pharmacy
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2016-11-14
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Hungary - National Institute of Pharmacy

A.2

EudraCT number

2016-002579-83

A.3

Full title of the trial

A Phase 1b/2, Open-Label, Randomized Study of Daratumumab Administered in Combination with Atezolizumab Compared with Atezolizumab Alone in Subjects with Previously Treated Advanced or Metastatic Non-Small Cell Lung Cancer

Az atezolizumabbal kombináltan alkalmazott daratumumab, illetve az önmagában alkalmazott atezolizumab 1b/2 fázisú, nyílt címkés randomizált vizsgálata a korábban már kezelt, előrehaladott vagy metasztázisos, nem kis sejtes tüdőrákban szenvedő betegeknél

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

A study of Daratumumab combined with Atezolizumab versus Atezolizumab in Previously Treated Subjects with Advanced Non-Small Cell Lung Cancer.

Az atezolizumabbal kombináltan alkalmazott daratumumab, illetve az önmagában alkalmazott atezolizumab vizsgálata a korábban már kezelt, előrehaladott nem kis sejtes tüdőrákban szenvedő betegeknél

A.3.2

Name or abbreviated title of the trial where available

CALLISTO

A.4.1

Sponsor's protocol code number

54767414LUC2001

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Janssen-Cilag International NV
B.1.3.4	Country	Belgium
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Janssen Research & Development
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	PAREXEL International LLC
B.5.2	Functional name of contact point
B.5.6	E-mail	clinicaltrial.enquiries@PAREXEL.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Daratumumab
D.3.4	Pharmaceutical form	Concentrate for solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	DARATUMUMAB
D.3.9.1	CAS number	945721-28-8
D.3.9.2	Current sponsor code	JNJ-54767414 (Daratumumab)
D.3.9.3	Other descriptive name	HUMAX-CD38
D.3.9.4	EV Substance Code	SUB175772
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	20
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Yes
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	Yes
D.3.11.13.1	Other medicinal product type	human monoclonal antibody
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Comparator
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	TECENTRIQ
D.2.1.1.2	Name of the Marketing Authorisation holder	Genentech
D.2.1.2	Country which granted the Marketing Authorisation	United States
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Atezolizumab
D.3.4	Pharmaceutical form	Concentrate for solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	ATEZOLIZUMAB
D.3.9.2	Current sponsor code	RO5541267
D.3.9.4	EV Substance Code	SUB178312
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	1200
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC)

E.1.1.1

Medical condition in easily understood language

A specific type of lung cancer called "Non-Small Cell Lung Cancer"

E.1.1.2

Therapeutic area

Diseases [C] - Cancer [C04]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	PT
E.1.2	Classification code	10029522
E.1.2	Term	Non-small cell lung cancer stage IV
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	PT
E.1.2	Classification code	10029521
E.1.2	Term	Non-small cell lung cancer stage IIIB
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To compare the overall response rate (ORR) in subjects treated with daratumumab in combination with atezolizumab versus atezolizumab alone.

E.2.2

Secondary objectives of the trial

- To assess the safety of the combination of daratumumab and atezolizumab
- To compare the duration of response (DoR) in subjects treated with daratumumab in combination with atezolizumab versus atezolizumab alone
- To compare the clinical benefit rate (CBR) in subjects treated with daratumumab in combination with atezolizumab versus atezolizumab alone
- To compare progression-free survival (PFS) in subjects treated with daratumumab in combination with atezolizumab versus atezolizumab alone
- To compare overall survival (OS) in subjects treated with daratumumab in combination with atezolizumab versus atezolizumab alone
- To evaluate the pharmacokinetic and immunogenicity profile of daratumumab when given in combination with atezolizumab
- To evaluate the pharmacokinetic and immunogenicity profile of atezolizumab when given in combination with daratumumab

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. ≥18 years of age
2. ECOG performance status of 0 or 1.
3. Have histologically or cytologically confirmed advanced or metastatic NSCLC (Stage IIIb or IV).
4. Measurable disease, as defined by RECIST v1.1.
5. Known PD-L1 tumor status as determined by an IHC assay performed by the central laboratory on tissue obtained at Screening.
6. Specific laboratory results obtained within 14 days prior to first administration of study drug.
7. A woman of childbearing potential must have a negative highly sensitive serum (b-human chorionic gonadotropin [b-hCG]) at Screening within 14 days prior to study drug administration.
8. Contraceptive use by men or women should be consistent with local regulations regarding the use of contraceptive methods for subject participating in clinical studies.
9. During the study and for a minimum of approximately 3 months after the last dose of daratumumab or 5 months after the last dose of atezolizumab, in addition to the highly effective method of contraception, a man
- who is sexually active with a woman of childbearing potential must agree to use a barrier method of contraception (eg, condom with spermicidal foam/gel/film/cream/suppository)
- who is sexually active with a woman who is pregnant must use a condom
- must agree not to donate sperm.
10. Willing and able to adhere to the prohibitions and restrictions specified in this protocol.
11. Must sign an informed consent form (ICF) indicating that he or she understands the purpose of, and procedures required for, the study and is willing to participate in the study.

E.4

Principal exclusion criteria

1. Received any of the following prescribed medications or therapies in
the past:
- Anti-CD38 therapy, including daratumumab
- CD137 agonists, immune checkpoint inhibitors including but not limited
to anti-CTLA-4, anti-PD-1, and anti-PD-L1 therapies
2. Received any of the following prescribed medications or therapies
within the specified period:
- Approved anti-cancer therapy, including chemotherapy, within 3 weeks
prior to first administration of study drug.
- Other investigational agent or participation in another clinical study
with therapeutic intent within 28 days or 5 half-lives of the
investigational agent (whichever is longer) prior to first administration
of study drug.
-Whole brain radiation within 28 days or other radiotherapy within 14
days prior to first administration of study drug.
-Use of systemic corticosteroids >10 mg/day prednisone equivalent
within 14 days prior to first administration of study drug.
3. Has any of the following conditions:
- Active or untreated CNS metastases as determined by computed
tomography (CT) or magnetic resonance imaging (MRI) evaluation.
- Leptomeningeal disease or spinal cord compression not definitively
treated with surgery or
radiation, or requiring corticosteroid treatment at first administration of
study drug.
- Uncontrolled tumor-related pain
4. Uncontrolled pleural effusion, pericardial effusion, or ascites requiring
recurrent drainage procedures (once monthly or more frequently);indwelling catheters are allowed.
5. Malignancies other than NSCLC within 2 years prior to first
administration of study drug, with
the exception of carcinoma in situ of the cervix or breast, basal or
squamous-cell skin cancer, or other malignancy that in the opinion of the
investigator and Sponsor is considered cured with a minimal risk of
recurrence within 5 years.
6. History of autoimmune disease.
7. History of pulmonary fibrosis, organizing pneumonia (eg, bronchiolitis
obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or
evidence of active pneumonitis on screening chest CT scan; history of
radiation pneumonitis in the radiation field (fibrosis) is permitted.
8. Known chronic obstructive pulmonary disease (COPD) with a forced
expiratory volume in
1 second (FEV1) <50% of predicted normal. Note that spirometry is
required during the screening
period for subjects suspected of having COPD and subjects must be
excluded if FEV1 <50% of
predicted normal.
9. Known to be seropositive for human immunodeficiency virus (HIV)
10. Active hepatitis B, defined by a positive test for hepatitis B surface
antigen (HBsAg) or prior
history of hepatitis B, defined by presence of antibodies to hepatitis B
core antigen [anti-HBc],
regardless of hepatitis B surface antibody [anti-HBs] status; active
hepatitis C or prior history of
hepatitis C (anti-HCV positive), except in the setting of a sustained
virologic response (SVR),
defined as aviremia 12 weeks after completion of antiviral therapy.
11. Severe infections (including active tuberculosis) within 1 week prior
to first administration of study drug.
12. Clinically significant cardiac disease, including myocardial infarction
within 6 months before first administration of study drug, or unstable or
uncontrolled disease/condition related to or affecting cardiac
function,uncontrolled cardiac arrhythmia or clinically significant ECG
abnormalities,a baseline corrected QT interval (QTc) >470 msec
13. Prior allogeneic bone marrow transplantation or solid organ
transplant.
14. Administration of a live, attenuated vaccine within 4 weeks before
first administration of study drug.
15. Women who are pregnant, lactating, or intending to become
pregnant during the study or within at least 3 months after last dose of
daratumumab or 5 months after the last dose of atezolizumab; men who
intend to father a child during the study or within at least 3 months after
the last dose of daratumumab or 5 months after the last dose of
atezolizumab.
16. History of severe allergic, anaphylactic, or other hypersensitivity
reactions to chimeric or humanized antibodies or fusion proteins.
17. Known hypersensitivity or allergy to biopharmaceuticals produced in
Chinese hamster ovary cells or any component of the daratumumab or
atezolizumab formulation.
18. Any other concurrent medical or psychiatric condition, diseases,
metabolic dysfunction, physical examination finding, or clinical
laboratory finding giving reasonable suspicion of a disease or condition
that contraindicates the use of an investigational drug or that may affect
the interpretation of the results or render the subject at high risk from
treatment complications.
19. Major surgery (eg, requiring general anesthesia) within 2 weeks
before Screening, not fully
recovered from surgery, or surgery planned during the time the subject
is expected to participate in the study or within 2 weeks after the last dose of study treatment.

E.5 End points

E.5.1

Primary end point(s)

The primary endpoint is ORR: the proportion of subjects with a partial response (PR) or complete response (CR) as defined by RECIST 1.1 response criteria

E.5.1.1

Timepoint(s) of evaluation of this end point

Throughout the whole study.

E.5.2

Secondary end point(s)

- Incidence of adverse events
- DoR: the duration from the date of the initial documentation of a response to the date of the first objectively documented evidence of recurrence or progressive disease or death, whichever status is recorded first.
- CBR: the proportion of subjects who achieve disease control (CR, PR, or SD with duration of at least 16 weeks).
- PFS: the duration from the date of randomization to the date of objectively documented progression or death due to any cause, whichever status is recorded first.
- OS: the duration from the date of randomization to the date of death due to any cause.
- Serum daratumumab concentration (Cmin, Cmax) and incidence of anti-daratumumab antibodies
- Serum atezolizumab concentration (Cmin, Cmax) and incidence of anti-atezolizumab antibodies

E.5.2.1

Timepoint(s) of evaluation of this end point

Throughout the whole study.

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

Yes

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

Yes

E.7.1.3.1

Other trial type description

Satefy run-in cohort to assess safety/tolerability of atezolizumab administered with daratumumab

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

Yes

E.8.2.2

Placebo

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

France

Hungary

Poland

Spain

United States

E.8.7

Trial has a data monitoring committee

Yes

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

Last patient last visit.

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

No post-trial medication will be provided, the further treatment of patients after end of trial will be carried out according to their physicians' decision.

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2017-01-25

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2017-01-05

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2019-09-26

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