COMBINATORY IMMUNOTHERAPY-2 (COM-IT-2) A phase 2 randomised open two-arm study to assess the tolerability and efficacy of immunotherapy combined with extensive radiotherapyfor the treatment of stage IV non-small cell lung cancer

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Oslo University Hospital HF

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Pathological Conditions, Signs and Symptoms [C23]

Trial duration

22 May 2024 → ongoing

Decision date (initial)

2024-05-21

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2023-510089-28-00

EudraCT number

2021-003266-13

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

The primary objective is to evaluate the acute toxicity (<3 months) and subacute toxicity (3-6 months) of immunotherapy combined with extensive radiotherapy in patients with stage IV NSCLC.

Secondary objectives 1

1. The secondary objectives are to evaluate measures of treatment effect (PFS, OS, DoR, ORR, TNT) and HRQoL between the treatment arms.

Conditions and MedDRA coding

Non-small cell lung cancer (Stage IV)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. • Stage IV NSCLC with clinical indication of starting systemic treatment with immunotherapy alone or in combination with chemotherapy (first or later lines)
2. • Available core or excisional biopsy of a tumour lesion
3. • Measurable disease according to RECIST criteria (RECIST 1.1)
4. • Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
5. • Life expectancy > 3 months
6. • At least 1 tumour lesion suitable for radiotherapy treatment
7. Age >18 years
8. Written informed consent
9. Adequate organ function based on clinical examination and lab values (o Hb>9 g/dL o Neutrophils >1500 pr mm3 o Estimated creatinine clearance >40 mL/min o AST and ALT <2.5 x upper normal limit (if liver metastases: AST/ALT must be <5x upper normal limit) o 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

Exclusion criteria 17

1. • Indication for radiotherapy other than stereotactic radiosurgery of brain metastases
2. • Significant cardiac, pulmonary or other medical illness that would limit activity or survival
3. • Previous treatment with PD1/PDL-1 inhibitor
4. • Radiotherapy given within the last 4 weeks prior to inclusion
5. • 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
6. • Patients with EGFR-mutation or ALK-translocation not previously treated with tyrosine kinase inhibitor
7. • Patients who test positive for hepatitis B, C or HIV
8. • 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
9. • Diagnosis of immunodeficiency or medical condition requiring high doses (>20 mg prednisolone daily) of systemic steroids or other forms of immunosuppressive therapy
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. Positive test is exclusion criterion.
11. Known hypersensitivity to the immunotherapy regimen planned for the patient the investigational product
12. Live vaccine administered last 30 days, active infection requiring IV antibiotics, active viral hepatitis or HIV
13. Previous allogenic or organ transplant
14. Any reason why, in the opinion of the investigator, the patient should not participate
15. Pregnancy or lactation
16. Treatment with any investigational medicinal product (IMP) that may interfere with the study treatment, within 2 weeks prior to first administration of study drug.
17. Disease suitable for curative salvage surgery

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary objective is to evaluate the acute toxicity (<3 months) and subacute toxicity (3-6 months) toxicity) of immunotherapy combined with extensive radiotherapy in patients with stage IV NSCLC compared with immunotherapy without radiotherapy.

Secondary endpoints 3

1. Adverse events and laboratory values will be graded according to the NCI-CTCAE version 5.0. and published
2. Response will be evaluated by iRECIST 1.1 and RECIST 1.1. Survival data (PFS and OS) and response rates (RR and DOR) will be evaluated and published.
3. HRQoL will be evaluated at baseline, end of radiotherapy and at 3 and 6 months for both study arms and published.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Oslo University Hospital HF

Sponsor organisation

Oslo University Hospital HF

Address

Taarnbygget, Kirkeveien 166 Kirkeveien 166

City

Oslo

Postcode

0450

Country

Norway

Scientific contact point

Organisation

Oslo University Hospital HF

Contact name

Department of Clinical Cancer Research

Public contact point

Organisation

Oslo University Hospital HF

Contact name

Department of Clinical Cancer Research

Locations

1 EU/EEA country · 3 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 13 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications