Phase II study: efficacy and safety of tislelizumab in patients with de novo Hodgkin lymphoma unsuitable for standard chemotherapy

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Fondazione Italiana Linfomi Onlus

Participant type

Patients

Age range

65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Hemic and Lymphatic Diseases [C15]

Trial duration

23 May 2024 → ongoing

Decision date (initial)

2023-11-16

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

BeOne Medicines

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy, Safety

The study is aimed at evaluating efficacy in terms of overall response rate (ORR) of tislelizumab as frontline treatment in patients with untreated Hodgkin Lymphoma (HL) considered unsuitable for chemotherapy.

Secondary objectives 5

1. To evaluate efficacy, as measured by the following and determined by investigator: duration of response (DoR)
2. To evaluate efficacy, as measured by the following and determined by investigator: progression-free survival (PFS)
3. To evaluate efficacy, as measured by the following and determined by investigator: overall survival (OS)
4. To evaluate efficacy, as measured by the following and determined by investigator: disease free survival (DFS)
5. To evaluate the safety and tolerability of tislelizumab

Conditions and MedDRA coding

Hodgkin lymphoma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. Histologically confirmed diagnosis of de novo classical Hodgkin Lymphoma (cHL)
2. Patients >= 65 years ineligible for frontline standard chemotherapy (mainly due to medical comorbidities)
3. Treatment naïve
4. Measurable disease defined as presence of both fluorodeoxyglucose-avid nodal involvement and at least one nodal target lesion measurable in two diameters (and at least 1.5 cm in its major diameter)
5. Indication for systemic treatment, i.e., all stages except IA without a large tumor burden, as radiotherapy is regarded curative in those patients
6. Eastern Cooperative Oncology Group (ECOG) performance status (PS) <= 2
7. Adequate organ and marrow function as defined below: Absolute neutrophil count (ANC) > 10 x 10^9/L (without growth factor support within 7 days of ANC measurement), unless due to bone marrow involvment by lymphoma; Platelet > 50 x 10^9/L (without growth factor support or transfusion within 7 days of platelets measurement), unless due to bone marrow involvment by lymphoma; Hemoglobin > 8 g/dL (prior transfusion is acceptable); Creatinine clearance ≥ 30 ml/min (as estimated by the Cockcroft-Gault equation or as measured by nuclear medicine scan or 24-hour urine collection); Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase, and alanine aminotransferase (ALT)/serum glutamic pyruvic transaminase ≤ 3.0 × upper limit of normal (ULN); Serum total bilirubin < 1.5 × ULN (or < 3 x ULN in case of documented Gilbert’s syndrome)
8. Life expectancy ≥ 6 months
9. Men must agree to use effective contraception if sexually active. This applies for the time period between signing of the informed consent form and 4 months after last tislelizumab dose.
10. Subject voluntarily signs and dates an informed consent form approved by an National Ethics Committee prior to the initiation of any screening or study-specific procedures, indicating that they understand the purpose of and procedures required for the study and are willing to participate in it
11. Subject must be able to adhere to the study visit schedule and other protocol requirements, and to return to enrolling institution for follow-up (during the active monitoring phase of the study)

Exclusion criteria 20

1. Nodular lymphocyte predominant HL
2. Hypersensitivity to tislelizumab or any of its excipients
3. Active central nervous system (CNS) involvement or leptomeningeal metastases involvement
4. Evidence of other clinically significant uncontrolled and/or active systemic infection (viral, bacterial or fungal), including active ongoing infection from SARS-CoV-2
5. Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
6. Major surgery within 4 weeks of the first dose of study drug
7. Vaccination with a live vaccine within 4 weeks prior to the first dose of study drug
8. Clinically significant cardiovascular disease including the following: Myocardial infarction within 6 months before screening; Unstable angina within 3 months before screening; New York Heart Association Classification III or IV congestive heart failure; History of clinically significant arrhythmias (e.g., sustained ventricular tachycardia, ventricular fibrillation, torsade de pointes); QTcF > 480 msecs based on Fridericia’s formula; History of Mobitz II second-degree or third-degree heart block without a permanent pacemaker in place; Uncontrolled hypertension as indicated by a minimum of 2 consecutive blood pressure measurements showing systolic blood pressure > 170 mm Hg and diastolic blood pressure > 105 mm Hg at screening
9. Significant history of neurologic, psychiatric, endocrinological, metabolic, immunologic, or hepatic disease that would preclude participation in the study or compromise ability to give informed consent
10. Any history of other active malignancies within 3 years prior to study entry, with the exception of adequately treated in situ carcinoma of the cervix uterine, basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin, previous malignancy confined and surgically resected with curative intent
11. Any previous treatment (including radiation therapy) for HL
12. History of severe hypersensitivity reactions to other monoclonal antibodies
13. Concurrent participation in another therapeutic clinical trial
14. Any active autoimmune disease requiring systemic treatment (including disease-modifying agents, corticosteroids, immunosuppressants) in the past 2 years. Note: Patients with the following diseases are not excluded and may proceed to further screening: type I diabetes under control; Hypothyroidism (provided it is managed with hormone replacement therapy only); Controlled celiac disease
15. Has known history of interstitial lung disease, non-infectious pneumonitis, pulmonary fibrosis, acute lung diseases or evidence of dyspnea at rest or pulse oximetry of < 92% while breathing room air
16. A history of previous exposure to anti-PD1, anti-PDL1 or anti-PDL2 or anti-CTLA-4 agents for any disease other than HL
17. Use of systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications ≤14 days from registration; Note: Inhaled or topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease
18. Known infection with HIV, human T-cell lymphotropic virus-1, -2
19. Serologic status reflecting active hepatitis B defined as presence of hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) (mandatory testing). Patients with occult or prior HBV infection (respectively defined as patient with HBsAg-/HBcAb+ and patients HBsAg+ with HBV DNA undetectable) are eligible, provided that they are willing to undergo prophylactic antiviral medication according to local standard of care. Patients who have protective titers of hepatitis B surface antibody (HBsAb) after vaccination are eligible
20. Presence of hepatitis C virus (HCV) antibody (mandatory HCV antibody serology testing). Patients with presence of HCV antibody are eligible only if PCR is negative for HCV RNA

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary endpoint of the study is the ORR (the sum of complete response (CR) and partial response (PR) rate).

Secondary endpoints 5

1. Duration of response (DoR)
2. Progression Free Survival (PFS)
3. Overall Survival (OS)
4. Disease free survival (DFS)
5. Incidence and severity of adverse events occurred during therapy and up to 90 days after treatment and incidence and severity of serious adverse event occurred from the IC signed to the end of the study (LPLV)

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Fondazione Italiana Linfomi Onlus

Sponsor organisation

Fondazione Italiana Linfomi Onlus

Address

Piazza Filippo Turati 5

City

Alexandria

Postcode

15121

Country

Italy

Scientific contact point

Organisation

Fondazione Italiana Linfomi Onlus

Contact name

Prof. Pier Luigi Zinzani

Public contact point

Organisation

Fondazione Italiana Linfomi Onlus

Contact name

Prof. Pier Luigi Zinzani

Locations

1 EU/EEA country · 12 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 20 files

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

Application history

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