Clinical Trials Register

Summary
EudraCT Number:	2021-003266-13
Sponsor's Protocol Code Number:	Com-IT-2
National Competent Authority:	Norway - NOMA
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2021-07-01
Trial 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

Norway - NOMA

A.2

EudraCT number

2021-003266-13

A.3

Full title of the trial

A PHASE 2 RANDOMISED OPEN TWO-ARM STUDY TO ASSESS THE TOLERABILITY AND EFFICACY OF IMMUNOTHERAPY COMBINED WITH EXTENSIVE RADIATIOTHERAPY FOR THE TREATMENT OF STAGE IV NON-SMALL CELL LUNG CANCER

A.3.1

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

COMBINATORY IMMUNOTHERAPY-2 (COM-IT-2)

A.3.2

Name or abbreviated title of the trial where available

Com-IT-2

A.4.1

Sponsor's protocol code number

Com-IT-2

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	Oslo University Hospital
B.1.3.4	Country	Norway
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Oslo university Hospital
B.4.2	Country	Norway
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Oslo University Hospital
B.5.2	Functional name of contact point	National coordinator and PI
B.5.3	Address:
B.5.3.1	Street Address	Kirkveien 166
B.5.3.2	Town/ city	Oslo
B.5.3.3	Post code	0450 Oslo
B.5.3.4	Country	Norway
B.5.4	Telephone number	+4702770
B.5.6	E-mail	vdd@ous-hf.no

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.2.1.1.1	Trade name	Pembrolizumab (KEytruda)
D.2.1.1.2	Name of the Marketing Authorisation holder	MSD
D.2.1.2	Country which granted the Marketing Authorisation	Norway
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	Keytruda
D.3.4	Pharmaceutical form	Injection/infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	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.IMP: 2
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.2.1.1.1	Trade name	Atezolizumab (Tecentriq)
D.2.1.1.2	Name of the Marketing Authorisation holder	Roche
D.2.1.2	Country which granted the Marketing Authorisation	Norway
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.3.4	Pharmaceutical form	Injection/infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	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.IMP: 3
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.2.1.1.1	Trade name	Nivolumab (Opdivio)
D.2.1.1.2	Name of the Marketing Authorisation holder	BMS
D.2.1.2	Country which granted the Marketing Authorisation	Norway
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.3.4	Pharmaceutical form	Injection/infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	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.IMP: 4
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.2.1.1.1	Trade name	Libtayo (Cemiplimab)
D.2.1.1.2	Name of the Marketing Authorisation holder	Regeneron Ireland Designated Activity Company (DAC)
D.2.1.2	Country which granted the Marketing Authorisation	Norway
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	Libtayo - Cemiplimab
D.3.4	Pharmaceutical form	Injection/infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	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

Non small cell lung cancer, stage IV
Patients are eligible if when they are planned to start immunotherapy according to standard routines and are not in need of radiotherapy

E.1.1.1

Medical condition in easily understood language

Non small cell lung cancer with extensive disease (metastases) and when immunotherapy is planned to start

E.1.1.2

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

MedDRA Classification

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

The aim of the trial is to study the acute and subacute toxicity of adding extensive radiotherapy to immunotherapy in the treatment of non small cell lung cancer with stage IV disease

E.2.2

Secondary objectives of the trial

The secondary objectives are to study the effect and quality of life of the treatment in question.
Specifically, secondary objectives are to evaluate:
- progression free survival and overall survival
- response rate, duration of respons
- Time to NeXT treatment
- Health related quality of life
- therapy response in non-irradiated lesions, if any
Exploratory objectives: Investigate
- biomarkers of treatment response
- immune response
- imaging to predict therapy response
- ctDNA as a tool to monitoring treatment effect

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Age >18 years
2. Written informed consent
3. Advanced NSCLC with clinical indication of starting systemic treatment with immunotherapy alone or in combination with chemotherapy (first or later lines)
4. Available core or excisional biopsy of a tumour lesion
5. Measurable disease according to RECIST criteria (RECIST 1.1)
6. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
7. Life expectancy > 3 months
8. At least 1 tumour lesion suitable for radiotherapy treatment
9. Adequate organ function based on clinical examination and lab values
Hb>9 g/dL
Neutrophils >1500 pr mm3
Estimated creatinin clearance >40 mL/min
AST and ALT <2.5 x upper normal limit (if liver metastases: AST/ALT must be <5x upper normal limit)
Serum bilirubin < 1.5 x upper normal limit
10. Women of childbearing potential (WOCBP) should use a highly effective method during the treatment period and for at least 5 months after the last dose of immunotherapy to avoid pregnancy. Methods considered as highly effective birth control methods include combined (estrogen and progestogen containing) or progestogen-only hormonal contraception associated with inhibition of ovulation (oral, intravaginal, injectable, implantable or transdermal), intrauterine device (including hormone-releasing), male condom, bilateral tubal occlusion, vasectomised partner or sexual abstinence
11. Able to understand oral and written information and able to answer questionnaires

E.4

Principal exclusion criteria

1. Disease suitable for curative salvage surgery
2. Indication for radiotherapy other than stereotactic radiosurgery of brain metastases
3. Treatment with any investigational medicinal product (IMP) that may interfere with the study treatment, within 2 weeks prior to first administration of study drug.
4. Expected use of anti-inflammatory medications as defined in 5.7.1 during the treatment period
5. Significant cardiac, pulmonary or other medical illness that would limit activity or survival
6. Previous treatment with PD1/PDL-1 inhibitor
7. Radiotherapy given within the last 4 weeks prior to inclusion
8. History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan
9. Pregnancy or lactation
10. Women who are not postmenopausal (postmenopausal defined as ≥ 12 months of non-drug-induced amenorrhea) or surgically sterile must have a negative serum pregnancy test result within 2 weeks prior to initiation of study drug
11. Patients with EGFR-mutation or ALK-translocation not previously treated with tyrosine kinase inhibitor
12. Known hypersensitivity to the immunotherapy regimen planned for the patient the investigational product
13. Patients who test positive for hepatitis B, C or HIV.
14. Known larger active brain metastases that cannot be treated with stereotactic radiotherapy. Patients with stable/previously treated brain metastases can be included. Patients with several smaller brain metastases may be included if the larger metastases are treated with stereotactic radiotherapy
15. Live vaccine administered last 30 days, active infection requiring IV antibiotics, active viral hepatitis or HIV
16. Previous allogenic or organ transplant
17. Diagnosis of immunodeficiency or medical condition requiring high doses (>20 mg prednisolone daily) of systemic steroids or other forms of immunosuppressive therapy
18. Any reason why, in the opinion of the investigator, the patient should not participate

E.5 End points

E.5.1

Primary end point(s)

Primary: Acute (<3 months) and subacute (3-6 months) toxicity

E.5.1.1

Timepoint(s) of evaluation of this end point

3-6 monts

E.5.2

Secondary end point(s)

PFS
OS
ORR
DoR
TNT
HR-QoL: EORTC QLQ-C30 and QLQ-LC29

E.5.2.1

Timepoint(s) of evaluation of this end point

3, 6 and 12, 18 and 24 months

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

E.6.7

Pharmacodynamic

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

Yes

E.6.13.1

Other scope of the trial description

The Scope of the trial is to evaluate if the toxicity of adding radiotherapy to immunotherapy leads to increased toxicity and if so, if the increased toxicity seems to be in proportion to the increase in treatment effect. This will be used to consider creating a phase 3 trial.

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

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)

E.8.2.2

Placebo

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

the comparator is without radiotherapy (the intervension arm is with radiotherapy)

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.8.5

The trial involves multiple Member States

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

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

The end of trial is defined as 1 year after the last patient’s last visit for treatment.

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

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.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)

Treatment after the trial will be according to local guidelines and be decided by the treating physician

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

2021-09-14

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2021-09-08

P. End of Trial
P.	End of Trial Status	Ongoing

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