NCT04313608

A Study Evaluating the Safety and Efficacy of Glofitamab or Mosunetuzumab in Combination With Gemcitabine Plus Oxaliplatin in Participants With Relapsed or Refractory Diffuse Large B-Cell Lymphoma and High-Grade Large B-Cell Lymphoma

Completed Phase 1 Results posted Last updated 25 March 2024

What this trial tests

Phase 1 trial testing Glofitamab in B-cell Lymphoma in 23 participants. Completed in 26 October 2021.

Timeline

4 June 2020

Primary endpoint
26 October 2021

26 October 2021

Quick facts

Lead sponsor	Hoffmann-La Roche
Phase	Phase 1
Status	Completed
Study type	INTERVENTIONAL
Allocation	non randomized
Design	sequential
Masking	none
Primary purpose	treatment
Enrollment	23
Start date	4 June 2020
Primary completion	26 October 2021
Estimated completion	26 October 2021
Sites	3 locations across Australia

Drugs / interventions tested

• Glofitamab (glofitamab) — full drug profile →
• Gemcitabine
• Oxaliplatin (Oxaliplatin) — full drug profile →
• Mosunetuzumab (MOSUNETUZUMAB) — full drug profile →
• Obinutuzumab — full drug profile →
• Tocilizumab (tocilizumab) — full drug profile →

Conditions studied

• B-cell Lymphoma — all drugs for B-cell Lymphoma →

Sponsor

Hoffmann-La Roche — full company profile →

Who can join

18 and older, any sex, with B-cell Lymphoma. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Deaths Due to Adverse Events (AEs) Primary · Baseline - 90 days after last dose of study treatment

An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Pre-existing conditions which worsen during a study are also considered as adverse events.

Group	Value	95% CI
Arm A: Glofit-GemOx	1
Arm B: Mosun-GemOx	0

Tolerability of Study Treatment as Measured by Dose Interruptions, Dose Reductions, and Treatment Discontinuation Due to AEs Secondary · Up to approximately 16 months

AEs leading to treatment discontinuation

Group	Value	95% CI
Arm A: Glofit-GemOx	5.9
Arm B: Mosun-GemOx	16.7

AEs leading to dose modification or interruption

Group	Value	95% CI
Arm A: Glofit-GemOx	29.4
Arm B: Mosun-GemOx	50.0

Complete Response (CR) Based on PET/CT as Determined by the Investigator According to the 2014 Lugano Response Criteria Secondary · Up to approximately 16 months

Per the 2014 Lugano Response Criteria for malignant lymphoma a CR = complete metabolic response with a score of 1, 2, or 3 on a 5-point scale (5PS), with higher scores indicating more extensive disease.

Group	Value	95% CI
Arm A: Glofit-GemOx	23.5	6.81 – 49.90
Arm B: Mosun-GemOx	50.0	11.81 – 88.19

Objective Response Rate (ORR), Defined as the Proportion of Participants With a Best Overall Response of Partial Response (PR) or CR, as Determined by the Investigator According to the 2014 Lugano Response Criteria Secondary · Up to approximately 16 months

Per the 2014 Lugano Response Criteria for malignant lymphoma a CR = complete metabolic response with a score of 1, 2, or 3 on a 5-point scale (5PS), while a PR = partial metabolic response with a score of 4 or 5 on 5PS with higher scores indicating more extensive disease.

Group	Value	95% CI
Arm A: Glofit-GemOx	35.3
Arm B: Mosun-GemOx	50.0

Maximum Serum Concentration (Cmax) of Glofitamab Secondary · Cycle 1 Day 8 and Cycle 2 Day 1

Pre-infusion Cycle 1 Day 8

Group	Value	95% CI
Arm A: Glofit-GemOx	0	0 – 0

Within 30 mins post infusion Cycle 1 Day 8

Group	Value	95% CI
Arm A: Glofit-GemOx	0.6	0.3 – 1.7

12 hours post infusion Cycle 1 Day 8

Group	Value	95% CI
Arm A: Glofit-GemOx	0.6	0.1 – 0.9

24 hours post infusion Cycle 1 Day 8

Group	Value	95% CI
Arm A: Glofit-GemOx	0.5	0.1 – 0.8

48 hours post infusion Cycle 1 Day 8

Group	Value	95% CI
Arm A: Glofit-GemOx	0.3	0 – 0.4

Pre-infusion Cycle 2 Day 1

Group	Value	95% CI
Arm A: Glofit-GemOx	0.8	0.1 – 1.3

Within 30 minutes post infusion Cycle 2 Day 1

Group	Value	95% CI
Arm A: Glofit-GemOx	9	6.8 – 17.7

6 hours post infusion Cycle 2 Day 1

Group	Value	95% CI
Arm A: Glofit-GemOx	7.8	5.5 – 13.1

Number of Treatment Discontinuations Due to AE Primary · Baseline - 90 days after last dose of study treatment

An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Pre-existing conditions which worsen during a study are also considered as adverse events.

Group	Value	95% CI
Arm A: Glofit-GemOx	1
Arm B: Mosun-GemOx	1

Proportion of Participants With Serious Adverse Events (SAEs) Primary · Baseline - 90 days after last dose of study treatment

An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Pre-existing conditions which worsen during a study are also considered as adverse events.

Group	Value	95% CI
Arm A: Glofit-GemOx	70.6
Arm B: Mosun-GemOx	66.7

Proportion of Participants With Cytokine Release Syndrome (CRS) by Grade of Severity Primary · Baseline - 90 days after last dose of study treatment

Severity of CRS was determined according to the American Society for Transplantation and Cell Therapy (ASTCT) Consensus Grading Criteria, in which Grade 1 as fever (≥38.0°C) with or without other symptoms; Grade 2 as fever with hypotension not requiring vasopressors and/or hypoxia requiring the use of oxygen (low-flow); and Grade 3 as fever with hypotension requiring one vasopressor with or without vasopressin and/or hypoxia requiring the use of oxygen (high-flow).

Grade 1

Group	Value	95% CI
Arm A: Glofit-GemOx	29.4
Arm B: Mosun-GemOx	16.7

Grade 2

Group	Value	95% CI
Arm A: Glofit-GemOx	11.8
Arm B: Mosun-GemOx	0

Grade 3

Group	Value	95% CI
Arm A: Glofit-GemOx	5.9
Arm B: Mosun-GemOx	0

Adverse events — posted to ClinicalTrials.gov

Time frame: Baseline - 90 days after the final dose of study treatment. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Arm A: Glofit-GemOx

Serious: 12/17 (71%)

Deaths: 1/17

Arm B: Mosun-GemOx

Serious: 4/6 (67%)

Deaths: 0/6

Serious adverse events (21 terms)

Reaction	System	Arm A: Glofit-GemOx	Arm B: Mosun-GemOx
Pyrexia	General disorders	—	—
Sepsis	Infections and infestations	—	—
Neutropenia	Blood and lymphatic system disorders	—	—
Colitis	Gastrointestinal disorders	—	—
Cytokine release syndrome	Immune system disorders	—	—
Fall	Injury, poisoning and procedural complications	—	—
Thrombocytopenia	Blood and lymphatic system disorders	—	—
Diarrhoea	Gastrointestinal disorders	—	—
Vomiting	Gastrointestinal disorders	—	—
Asthenia	General disorders	—	—
Hepatic cirrhosis	Hepatobiliary disorders	—	—
Cellulitis	Infections and infestations	—	—
Neutropenic sepsis	Infections and infestations	—	—
Urinary tract infection	Infections and infestations	—	—
Wound infection	Infections and infestations	—	—
Tumour lysis syndrome	Metabolism and nutrition disorders	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—
Squamous cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—
Immune effector cell-associated neurotoxicity syndrome	Nervous system disorders	—	—
Transient ischaemic attack	Nervous system disorders	—	—
Orthostatic hypotension	Vascular disorders	—	—

Other adverse events (104 terms — click to expand)

Reaction	System	Arm A: Glofit-GemOx	Arm B: Mosun-GemOx
Cytokine release syndrome	Immune system disorders	—	—
Anaemia	Blood and lymphatic system disorders	—	—
Diarrhoea	Gastrointestinal disorders	—	—
Hypomagnesaemia	Metabolism and nutrition disorders	—	—
Neuropathy peripheral	Nervous system disorders	—	—
Neutropenia	Blood and lymphatic system disorders	—	—
Thrombocytopenia	Blood and lymphatic system disorders	—	—
Constipation	Gastrointestinal disorders	—	—
Nausea	Gastrointestinal disorders	—	—
Fatigue	General disorders	—	—
Liver function test abnormal	Investigations	—	—
Platelet count decreased	Investigations	—	—
Hypophosphataemia	Metabolism and nutrition disorders	—	—
Oral candidiasis	Infections and infestations	—	—
Urinary tract infection	Infections and infestations	—	—
Neutrophil count decreased	Investigations	—	—
Weight decreased	Investigations	—	—
Hypokalaemia	Metabolism and nutrition disorders	—	—
Arthralgia	Musculoskeletal and connective tissue disorders	—	—
Headache	Nervous system disorders	—	—
Lethargy	Nervous system disorders	—	—
Peripheral sensory neuropathy	Nervous system disorders	—	—
Abdominal discomfort	Gastrointestinal disorders	—	—
Abdominal pain	Gastrointestinal disorders	—	—
Gastrooesophageal reflux disease	Gastrointestinal disorders	—	—
Rectal haemorrhage	Gastrointestinal disorders	—	—
Vomiting	Gastrointestinal disorders	—	—
Oedema peripheral	General disorders	—	—
Candida infection	Infections and infestations	—	—
Contusion	Injury, poisoning and procedural complications	—	—
Fall	Injury, poisoning and procedural complications	—	—
Infusion related reaction	Injury, poisoning and procedural complications	—	—
Alanine aminotransferase increased	Investigations	—	—
Aspartate aminotransferase increased	Investigations	—	—
Blood alkaline phosphatase increased	Investigations	—	—
Pain in extremity	Musculoskeletal and connective tissue disorders	—	—
Dizziness	Nervous system disorders	—	—
Paraesthesia	Nervous system disorders	—	—
Cough	Respiratory, thoracic and mediastinal disorders	—	—
Flushing	Vascular disorders	—	—

Most-reported serious reactions: Pyrexia, Sepsis, Neutropenia, Colitis, Cytokine release syndrome, Fall, Thrombocytopenia, Diarrhoea.

Data from ClinicalTrials.gov NCT04313608 adverse events section.

Sponsor's own description

This study is designed to evaluate the safety and efficacy of glofitamab or mosunetuzumab in combination with gemcitabine and oxaliplatin (Glofit-GemOx or Mosun-GemOx) in participants with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) or high-grade B-cell lymphoma (HGBCL).

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Glofitamab, a Novel, Bivalent CD20-Targeting T-Cell-Engaging Bispecific Antibody, Induces Durable Complete Remissions in Relapsed or Refractory B-Cell Lymphoma: A Phase I Trial.
   Hutchings M, Morschhauser F, Iacoboni G, Carlo-Stella C, et al · · 2021 · cited 328× · PMID 33739857 · DOI 10.1200/jco.20.03175
2. Emerging new therapeutic antibody derivatives for cancer treatment.
   Jin S, Sun Y, Liang X, Gu X, et al · · 2022 · cited 304× · PMID 35132063 · DOI 10.1038/s41392-021-00868-x
3. Single-Agent Mosunetuzumab Shows Durable Complete Responses in Patients With Relapsed or Refractory B-Cell Lymphomas: Phase I Dose-Escalation Study.
   Budde LE, Assouline S, Sehn LH, Schuster SJ, et al · · 2022 · cited 241× · PMID 34914545 · DOI 10.1200/jco.21.00931
4. Overcoming the challenges associated with CD3+ T-cell redirection in cancer.
   Singh A, Dees S, Grewal IS. · · 2021 · cited 82× · PMID 33469153 · DOI 10.1038/s41416-020-01225-5
5. Bispecific Antibodies: A Review of Development, Clinical Efficacy and Toxicity in B-Cell Lymphomas.
   Salvaris R, Ong J, Gregory GP. · · 2021 · cited 62× · PMID 33946635 · DOI 10.3390/jpm11050355
6. Glofitamab: First Approval.
   Shirley M. · · 2023 · cited 41× · PMID 37285013 · DOI 10.1007/s40265-023-01894-5
7. DLBCL 1L-What to Expect beyond R-CHOP?
   Stegemann M, Denker S, Schmitt CA. · · 2022 · cited 28× · PMID 35326604 · DOI 10.3390/cancers14061453
8. Relapsed/Refractory Diffuse Large B-Cell Lymphoma: A Look at the Approved and Emerging Therapies.
   Sawalha Y. · · 2021 · cited 25× · PMID 34945817 · DOI 10.3390/jpm11121345