A Study of Glofitamab (RO7082859) and Atezolizumab or Polatuzumab Vedotin (Plus A Single Pretreatment Dose of Obinutuzumab) in Adult Patients with Relapsed/Refractory B-Cell Non-Hodgkin’s Lymphoma

Overview

Sponsor-declared trial summary

Key facts

Sponsor

F. Hoffmann-La Roche AG

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

23 Apr 2018 → ongoing

Decision date (initial)

2024-03-29

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

F. Hoffmann-La Roche Ltd

External identifiers

EU CT number

2023-505222-34-00

EudraCT number

2017-004835-36

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Others, Pharmacodynamic, Safety, Efficacy

To evaluate the efficacy of glofitamab in combination with polatuzumab vedotin (including a single pretreatment dose of obinutuzumab) in patients diagnosed with R/R large B-cell lymphoma (LBCL) diffuse large B-cell lymphoma (DLBCL) NOS, high-grade B-cell lymphoma (HGBCL), primary mediastinal large B-cell lymphoma (PMBCL), and transformed follicular lymphoma (trFL) as measured by IRC-assessed best ORR according to standard NHL response criteriaTo determine the maximum tolerated dose (MTD) and/or recommended Phase II dose (RP2D) for glofitamab in combination with atezolizumab or polatuzumab vedotin (including a single pretreatment dose of obinutuzumab)
To determine the maximum tolerated dose (MTD) and/or recommended Phase II dose (RP2D) for glofitamab in combination with atezolizumab or polatuzumab vedotin (including a single pretreatment dose of obinutuzumab)

Secondary objectives 9

1. To evaluate the efficacy of glofitamab in combination with polatuzumab vedotin (including a single pretreatment dose of obinutuzumab) diagnosed with R/R LBCL (DLBCL NOS, HGBCL, PMBCL, and trFL) as measured by IRC and Investigator
2. To evaluate the safety and tolerability of glofitamab in combination with atezolizumab or polatuzumab vedotin (including a single pretreatment dose of obinutuzumab)
3. To assess preliminary anti-tumor activity of glofitamab in combination with atezolizumab (including a single pretreatment dose of obinutuzumab) in R/R NHL as measured by Investigator
4. To characterize the pharmacokinetics (PK) of glofitamab when administered in combination with atezolizumab or polatuzumab vedotin
5. To characterize the PK of atezolizumab and polatuzumab vedotin when administered in combination with glofitamab
6. To assess mode of action of glofitamab in combination with atezolizumab or polatuzumab vedotin
7. Glofitamab Imaging Sub-Study NP39488/IMG: To evaluate the safety and tolerability of repeated doses of 89Zr-Df-IAB22M2C
8. Glofitamab Imaging Sub-Study NP39488/IMG: To assess the relationship between 89Zr-Df- IAB22M2C PET/CT and CD8+ cells and thereby also determine the sensitivity of 89Zr-Df-IAB22M2C
9. Glofitamab Imaging Sub-Study NP39488/IMG: To relate increase of 89Zr-Df-IAB22M2C PET uptake to clinical outcomes with glofitamab and atezolizumab treatment

Conditions and MedDRA coding

Relapsed/refractory (r/r) B-cell Non-Hodgkin’s Lymphoma (NHL)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Eastern Cooperative Oncology Group performance status of 0, 1, or 2
2. Life expectancy of >= 12 weeks
3. Adequate liver function, hematological function, renal function
4. Negative serologic and/or polymerase chain reaction test results for acute or chronic hepatitis B virus (HBV) infection
5. Negative test results for hepatitis C virus (HCV) and Human immunodeficiency virus (HIV)
6. Negative HIV test at screening, with the following exception: - Individuals with a positive HIV test at screening are eligible provided they are stable on antiretroviral therapy for at least 4 weeks, have a CD4 count = 200/mL, have an undetectable viral load, and have not had a history of opportunistic infection attributable to AIDS within the last 12 months - Patients with positive HIV at screening should be monitored while receiving study treatment. HIV viral load will be performed every 3 months (± 4 weeks) in the first 6 months and subsequently every 6 months (± 4 weeks) until end of study treatment. If HIV viral load is detected (positive), the patient should be treated per local institutional standards,and the Medical Monitor should be notified. Testing may be performed at the local institution. If local laboratory assessments are not available for testing, local laboratory collections may be waived only if samples are collected for central laboratory assessments of viral infections

Exclusion criteria 6

1. Patients with chronic lymphocytic leukemia, acute lymphoblastic leukemia (ALL) (including CD20+ ALL), lymphoblastic lymphoma, Richter’s transformation, Burkitt lymphoma or lymphoplasmacytic lymphoma
2. Patients with known active infection, or reactivation of a latent infection, whether bacterial, viral, fungal, mycobacterial, or other pathogens or any major episode of infection requiring hospitalization or treatment with IV antibiotics within 4 weeks prior to obinutuzumab (Gazyva, Gazyvaro) pretreatment (Gpt) infusion. Note: Exclusion of patients with mycobacterial infections on the basis of chest X-ray or CT or on the basis of a positive Quantiferon or Mantoux test
3. Current Grade > 1 peripheral neuropathy (only for patients being treated in the polatuzumab vedotin arm)
4. Patient with history of confirmed progressive multifocal leukoencephalopathy (PML)
5. History of leptomeningeal disease, current or past history of central nervous system (CNS) lymphoma and CNS disease, such as stroke, epilepsy, CNS vasculitis, or neurodegenerative disease
6. Major surgery or significant traumatic injury <= 28 days prior to Gpt infusion or anticipation of the need for major surgery during study treatment

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. 1. Best ORR (CR or PR) based on PET-CT and/or CT scan as determined by the IRC using Lugano 2014 criteria
2. 2. Incidence and nature of dose-limiting toxicities (DLTs) during the DLT observation period

Secondary endpoints 21

1. 1. Best ORR (CR or PR at any time in the study) based on PET-CT and/or CT scan, as determined by the investigator
2. 2. Best CR rate on study based on PET-CT and/or CT scan, as determined by the investigator and IRC
3. 3. DOCR, defined as the time from the first occurrence of a documented complete response to disease progression \ or death from any cause, whichever occurs first as determined by the investigator and IRC
4. 4. DOR, defined as the time from the first occurrence of a documented objective response to disease progression as determined by the investigator and IRC
5. 5. PFS, defined as the time from first study treatment to the first occurrence of disease progression, or death from any cause, whichever occurs first as determined by the investigator and IRC
6. 6. EFS, defined as the time from first study treatment to the first occurrence of disease progression, or relapse initiation of NALT, or death from any cause, whichever occurs first, determined by the investigator and IRC
7. 7. Time to first complete response (TFCR), defined as time from the start of treatment to the first CR among complete responders, determined by the investigator and IRC
8. 8. Time to first overall response (TFOR), defined as the first treatment to first response among responders, determined by the investigator and IRC
9. 9. OS, defined as the time from first study treatment to death from any cause
10. 10. Incidence, nature, frequency, severity, and timing of AEs and serious adverse events (SAEs) graded according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4
11. 11. Incidence and severity of CRS following glofitamab administration, with severity determined according to ASTCT criteria (Lee et al. 2019; Appendix 6)
12. 12. Changes in vital signs, electrocardiograms, and clinical laboratory results during and following study treatment administration
13. 13. Incidence of anti-drug antibody formation
14. 14. Elimination half-life
15. 15. Total serum exposure - Area under the concentration-time curve
16. 16. Time to maximum observed serum concentration
17. 17. Maximum serum concentration observed
18. 18. Minimum serum concentration under steady-state conditions within a dosing interval
19. 19. Other PK parameters such as clearance (CL), and volume of distribution at steady state (Vss), may also be calculated as data allow.
20. 20. CD8-positive T-cell proliferation in tumor tissue and blood
21. 21. B-cell reduction in blood and tumor tissue

Investigational products

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

Test 6

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

F. Hoffmann-La Roche AG

Sponsor organisation

F. Hoffmann-La Roche AG

Address

Grenzacherstrasse 124

City

Basel

Postcode

4058

Country

Switzerland

Scientific contact point

Organisation

F. Hoffmann-La Roche AG

Contact name

Trial Information System - TISL

Public contact point

Organisation

F. Hoffmann-La Roche AG

Contact name

Trial Information System - TISL

Third parties 13

Locations

4 EU/EEA countries · 13 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 81 files

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

Application history

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