Nivolumab and ipilimumab +/- UV1 vaccination as second line treatment in patients with malignant mesothelioma (the NIPU-study)

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] - Neoplasms [C04], Diseases [C] - Respiratory Tract Diseases [C08]

Trial duration

20 Dec 2019 → ongoing

Decision date (initial)

2023-02-20

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Funding sources

Ultimovacs · South-Eastern Norway Regional Health Authority · Bristol-Myers Squibb Pharmaceuticals Ltd.

External identifiers

EU CT number

2022-502604-67-00

EudraCT number

2019-002721-30

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Therapy

To evaluate and compare the efficacy of nivolumab and ipilimumab with or without UV1-vaccine in patients with inoperable malignant pleural mesothelioma progressing after first-line platinum-based chemotherapy.

Secondary objectives 3

1. To compare overall survival (OS), objective response rate (ORR), disease control rate (DCR), time to response (TTR) and duration of response (DOR) according to Response Evaluation Criteria in Solid Tumours, version 1.1 (Modified RECIST), in patients who receive nivlumab and ipilimumab with patients who receive nivolumab and ipilimumab in combination with UV1.
2. To evaluate changes from baseline in patient-reported outcomes (PROs) of lung cancer symptoms, patient functioning, and health-related quality of life (HRQoL) in patients who receive nivlumab and ipilimumab compared to patients who receive nivolumab and ipilimumab in combination with UV1.
3. To determine the safety and tolerability in patients who receive nivlumab and ipilimumab compared to patients who receive nivolumab and ipilimumab in combination with UV1.

Conditions and MedDRA coding

Malignant pleural mesothelioma (MPM)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. Histologically and/or cytologically confirmed malignant pleural mesothelioma.
2. Unresectable disease (defined as the participant not being a candidate for curative surgery).
3. Measurable disease, defined as at least 1 lesion (measurable) that can be accurately assessed at baseline by computed tomography (CT) or magnetic resonance imaging (MRI) and is suitable for repeated assessment (modified RECIST).
4. Available unstained archived tumour tissue sample in sufficient quantity to allow for analyses. At least fifteen unstained slides or a tumour block (preferred). NOTE: A fine needle aspiration sample is not sufficient to make the patient eligible for enrollment. Given the complexity of mesothelioma pathological diagnosis , it is expected that they will have a core needle biopsy or surgical tumour biopsy as part of their initial diagnostic work up.
5. Age ≥ 18 years.
6. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
7. Willing to provide archived tumour tissue and blood samples for research.
8. Adequate organ function as defined below − Haemoglobin ≥9.0 g/dL − Absolute neutrophil count (ANC) 1.5 (or 1.0) x (> 1500 per mm3) − Platelet count ≥100 (or 75) x 109/L (>75,000 per mm3) − Serum bilirubin ≤1.5 x institutional upper limit of normal (ULN). − AST (SGOT)/ALT (SGPT) ≤2.5 x institutional upper limit of normal unless liver metastases are present, in which case it must be ≤5x ULN − Measured creatinine clearance (CL) >40 mL/min or Calculated creatinine CL>40 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urine collection for determination of creatinine clearance: Males: Creatinine CL (mL/min) = Weight (kg) x (140 – Age) 72 x serum creatinine (mg/dL) Females: Creatinine CL (mL/min) = Weight (kg) x (140 – Age) x 0.85 72 x serum creatinine (mg/dL)
9. Previously treated with at least one line of platinum -pemetrexed

Exclusion criteria 17

1. Disease suitable for curative surgery.
2. Uncontrolled seizures.
3. Current or prior use of immunosuppressive medication within 28 days before the first dose of nivolumab, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid. Standard steroid premedication given prior to chemotherapy or as prophylaxis for imaging contrast allergy should not be counted for this criterion.
4. Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease, diverticulitis with the exception of diverticulosis, celiac disease, irritable bowel disease; Wegner syndrome) within the past 2 years. Subjects with vitiligo, alopecia, Grave's disease, or psoriasis not requiring systemic treatment (within the past 3 years) are not excluded.
5. Known history of leptomeningeal carcinomatosis.
6. Pregnant or lactating women.
7. Live attenuated vaccination within 30 days prior to study entry or within 30 days of receiving nivolumab.
8. History of primary immunodeficiency.
9. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis, active bleeding diatheses including any subject known to have psychiatric illness/social situations that would limit compliance with study requirements or compromise the ability of the subject to give written informed consent.
10. Active infection including tuberculosis (clinical evaluation including: physical examination findings, radiographic findings, positive PPD test, etc.), hepatitis B (known positive HBV surface antigen [HBsAg] result), hepatitis C, or human immunodeficiency virus (positive HIV 1/2 antibodies as defined by a positive ELISA test). Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible. Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA. HIV testing is not required in the absence of clinical suspicion.
11. History of allogeneic organ transplant.
12. Previous treatment with a PD-1 or PD-L1 inhibitor, including nivolumab or any other agent targeting immune checkpoints.
13. Non-pleural mesothelioma e.g. mesothelioma arising in peritoneum, tunica vaginalis or any serosal surface other than the pleura.
14. Active second malignancy other than non-melanoma skin cancer or cervical carcinoma in situ.
15. Symptomatic or uncontrolled brain metastases requiring concurrent treatment, inclusive of but not limited to surgery, radiation and/or corticosteroids (prednisone >10 mg or equivalent). Surgery, radiation and/or corticosteroids (any dose >10 mg prednisone equivalent) must have been completed ≥ 2 weeks prior to registration.
16. Any condition that, in the opinion of the investigator, would interfere with the evaluation of study treatment or interpretation of patient safety or study results.
17. History of allergy or hypersensitivity to any of the active substances or excipients in the study drug.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Progression-free survival (PFS) per Modified Response Evaluation Criteria in Solid Tumours (RECIST) as determined by blinded independent central review (BICR).

Secondary endpoints 4

1. Overall survival (OS), objective response rate (ORR), disease control rate (DCR), time to response (TTR) and duration of response (DOR).
2. European Organisation for Research and Treatment of Cancer (EORTC) Quality-of-Life Questionnaire Core 30 (QLQ-C30) and it's Lung Cancer Module (LC13) scores.
3. Adverse events (AEs).
4. Study drug discontinuations due to AEs.

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

Åslaug Helland

Public contact point

Organisation

Oslo University Hospital Hf

Contact name

Åslaug Helland

Locations

4 EU/EEA countries · 5 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 4 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