Trial Outcomes & Findings for PNT2258 for Treatment of Patients With r/r DLBCL (Wolverine) (NCT NCT02226965)
NCT ID: NCT02226965
Last Updated: 2023-06-29
Results Overview
The proportion of patients with complete response (CR/complete metabolic response \[CMR\]) or partial response (PR/partial metabolic response \[PMR\]) according to the revised 2014 International Working Group (IWG) criteria for lymphoma (Cheson 2014)
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
45 participants
Primary outcome timeframe
19 months
Results posted on
2023-06-29
Participant Flow
The study was initiated in December 2014 and the first subject was enrolled on 10 December 2014. A total of 60 subjects were screened. Enrollment was closed as of 07 June 2016. Subjects were enrolled at oncology clinics in the USA.
Participant milestones
| Measure |
PNT2258
PNT2258 was administered at a dose of 120 mg/m2, as a 3 - 4 hour intravenous (IV) infusion on days 1 through 5 of 21-day induction phase cycles (for eight cycles), followed by continuation phase therapy at a dose of 100 mg/m2, as a 2 - 3 hour intravenous (IV) infusion on days 1 through 4 of a 28-day cycle.
|
|---|---|
|
Overall Study
STARTED
|
45
|
|
Overall Study
COMPLETED
|
4
|
|
Overall Study
NOT COMPLETED
|
41
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
PNT2258 for Treatment of Patients With r/r DLBCL (Wolverine)
Baseline characteristics by cohort
| Measure |
PNT2258
n=45 Participants
PNT2258 was administered at a dose of 120 mg/m2, as a 3 - 4 hour intravenous (IV) infusion on days 1 through 5 of 21-day induction phase cycles (for eight cycles), followed by continuation phase therapy at a dose of 100 mg/m2, as a 2 - 3 hour intravenous (IV) infusion on days 1 through 4 of a 28-day cycle.
|
|---|---|
|
Age, Continuous
|
64 years
n=93 Participants
|
|
Sex: Female, Male
Female
|
29 Participants
n=93 Participants
|
|
Sex: Female, Male
Male
|
16 Participants
n=93 Participants
|
PRIMARY outcome
Timeframe: 19 monthsPopulation: All enrolled population: All patients who passed the screening in the study
The proportion of patients with complete response (CR/complete metabolic response \[CMR\]) or partial response (PR/partial metabolic response \[PMR\]) according to the revised 2014 International Working Group (IWG) criteria for lymphoma (Cheson 2014)
Outcome measures
| Measure |
PNT2258
n=45 Participants
PNT2258 was administered at a dose of 120 mg/m2, as a 3 - 4 hour intravenous (IV) infusion on days 1 through 5 of 21-day induction phase cycles (for eight cycles), followed by continuation phase therapy at a dose of 100 mg/m2, as a 2 - 3 hour intravenous (IV) infusion on days 1 through 4 of a 28-day cycle.
|
|---|---|
|
Overall Response Rate
|
11.1 percentage of participants
Interval 3.7 to 24.1
|
SECONDARY outcome
Timeframe: 19 monthsPopulation: All enrolled population: All patients who passed the screening in the study
The proportion of patients who have a response of stable disease (SD/no metabolic response \[NMR\]) or better by investigator assessment
Outcome measures
| Measure |
PNT2258
n=45 Participants
PNT2258 was administered at a dose of 120 mg/m2, as a 3 - 4 hour intravenous (IV) infusion on days 1 through 5 of 21-day induction phase cycles (for eight cycles), followed by continuation phase therapy at a dose of 100 mg/m2, as a 2 - 3 hour intravenous (IV) infusion on days 1 through 4 of a 28-day cycle.
|
|---|---|
|
Disease Control Rate
|
20.0 percentage of participants
Interval 9.6 to 34.6
|
SECONDARY outcome
Timeframe: 19 monthsPopulation: All enrolled population: All patients who passed the screening in the study
The number of months from Cycle 1 Day 1 until the date of the first documented response
Outcome measures
| Measure |
PNT2258
n=45 Participants
PNT2258 was administered at a dose of 120 mg/m2, as a 3 - 4 hour intravenous (IV) infusion on days 1 through 5 of 21-day induction phase cycles (for eight cycles), followed by continuation phase therapy at a dose of 100 mg/m2, as a 2 - 3 hour intravenous (IV) infusion on days 1 through 4 of a 28-day cycle.
|
|---|---|
|
Time to Response
|
2.2 months
Interval 1.9 to 5.4
|
SECONDARY outcome
Timeframe: 19 monthsPopulation: All enrolled population: All patients who passed the screening in the study
The number of months from C1D1 until the date of DLBCL progression or death from any cause, or to the last date at which progression status was adequately assessed for censored observation
Outcome measures
| Measure |
PNT2258
n=45 Participants
PNT2258 was administered at a dose of 120 mg/m2, as a 3 - 4 hour intravenous (IV) infusion on days 1 through 5 of 21-day induction phase cycles (for eight cycles), followed by continuation phase therapy at a dose of 100 mg/m2, as a 2 - 3 hour intravenous (IV) infusion on days 1 through 4 of a 28-day cycle.
|
|---|---|
|
Progression-free Survival
|
1.9 months
Interval 1.4 to 1.9
|
SECONDARY outcome
Timeframe: 36 monthsPopulation: Safety population: All patients who received at least 1 dose of PNT2258
Characterization of the type, frequency, severity, timing of onset, duration, and relationship to study drug of any treatment-emergent adverse events, laboratory abnormalities, serious adverse events or adverse events leading to discontinuation of study treatment
Outcome measures
| Measure |
PNT2258
n=45 Participants
PNT2258 was administered at a dose of 120 mg/m2, as a 3 - 4 hour intravenous (IV) infusion on days 1 through 5 of 21-day induction phase cycles (for eight cycles), followed by continuation phase therapy at a dose of 100 mg/m2, as a 2 - 3 hour intravenous (IV) infusion on days 1 through 4 of a 28-day cycle.
|
|---|---|
|
Safety - Assessment of Adverse Events
|
45 participants reporting at least 1 AE
|
SECONDARY outcome
Timeframe: 19 monthsPopulation: All enrolled population: All patients who passed the screening in the study
The number of months from C1D1 until the date of death from any cause, or to the last date at which survival status was adequately assessed for censored observations
Outcome measures
| Measure |
PNT2258
n=45 Participants
PNT2258 was administered at a dose of 120 mg/m2, as a 3 - 4 hour intravenous (IV) infusion on days 1 through 5 of 21-day induction phase cycles (for eight cycles), followed by continuation phase therapy at a dose of 100 mg/m2, as a 2 - 3 hour intravenous (IV) infusion on days 1 through 4 of a 28-day cycle.
|
|---|---|
|
Overall Survival
|
9.8 months
Interval 0.3 to 19.1
|
SECONDARY outcome
Timeframe: 19 monthsPopulation: All enrolled population: All patients who passed the screening in the study
The time from the initial CMR or PMR until the date of progression or death from any cause, or to the last date at which progression status was adequately assessed for censored observations
Outcome measures
| Measure |
PNT2258
n=45 Participants
PNT2258 was administered at a dose of 120 mg/m2, as a 3 - 4 hour intravenous (IV) infusion on days 1 through 5 of 21-day induction phase cycles (for eight cycles), followed by continuation phase therapy at a dose of 100 mg/m2, as a 2 - 3 hour intravenous (IV) infusion on days 1 through 4 of a 28-day cycle.
|
|---|---|
|
Duration of Overall Response
|
5.3 months
Interval 0.0 to 8.3
|
Adverse Events
PNT2258
Serious events: 18 serious events
Other events: 45 other events
Deaths: 11 deaths
Serious adverse events
| Measure |
PNT2258
n=45 participants at risk
PNT2258 was administered at a dose of 120 mg/m2, as a 3 - 4 hour intravenous (IV) infusion on days 1 through 5 of 21-day induction phase cycles (for eight cycles), followed by continuation phase therapy at a dose of 100 mg/m2, as a 2 - 3 hour intravenous (IV) infusion on days 1 through 4 of a 28-day cycle.
|
|---|---|
|
General disorders
Pyrexia
|
11.1%
5/45 • 24 months
Adverse events were collected until 30 days after the last dose of PNT2258 for each subject
|
|
Vascular disorders
Hypotension
|
6.7%
3/45 • 24 months
Adverse events were collected until 30 days after the last dose of PNT2258 for each subject
|
|
General disorders
Disease progression
|
6.7%
3/45 • 24 months
Adverse events were collected until 30 days after the last dose of PNT2258 for each subject
|
|
Infections and infestations
Sepsis
|
6.7%
3/45 • 24 months
Adverse events were collected until 30 days after the last dose of PNT2258 for each subject
|
|
Infections and infestations
Pneumonia
|
6.7%
3/45 • 24 months
Adverse events were collected until 30 days after the last dose of PNT2258 for each subject
|
|
Gastrointestinal disorders
Abdominal pain
|
4.4%
2/45 • 24 months
Adverse events were collected until 30 days after the last dose of PNT2258 for each subject
|
|
Metabolism and nutrition disorders
Failure to thrive
|
4.4%
2/45 • 24 months
Adverse events were collected until 30 days after the last dose of PNT2258 for each subject
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
4.4%
2/45 • 24 months
Adverse events were collected until 30 days after the last dose of PNT2258 for each subject
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumor flare
|
4.4%
2/45 • 24 months
Adverse events were collected until 30 days after the last dose of PNT2258 for each subject
|
|
Gastrointestinal disorders
Abdominal distension
|
2.2%
1/45 • 24 months
Adverse events were collected until 30 days after the last dose of PNT2258 for each subject
|
|
Renal and urinary disorders
Acute kidney injury
|
2.2%
1/45 • 24 months
Adverse events were collected until 30 days after the last dose of PNT2258 for each subject
|
|
Cardiac disorders
Atrial fibrillation
|
2.2%
1/45 • 24 months
Adverse events were collected until 30 days after the last dose of PNT2258 for each subject
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
2.2%
1/45 • 24 months
Adverse events were collected until 30 days after the last dose of PNT2258 for each subject
|
|
Infections and infestations
Cellulitis
|
2.2%
1/45 • 24 months
Adverse events were collected until 30 days after the last dose of PNT2258 for each subject
|
|
General disorders
Chills
|
2.2%
1/45 • 24 months
Adverse events were collected until 30 days after the last dose of PNT2258 for each subject
|
|
Gastrointestinal disorders
Colitis
|
2.2%
1/45 • 24 months
Adverse events were collected until 30 days after the last dose of PNT2258 for each subject
|
|
Metabolism and nutrition disorders
Dehydration
|
2.2%
1/45 • 24 months
Adverse events were collected until 30 days after the last dose of PNT2258 for each subject
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
2.2%
1/45 • 24 months
Adverse events were collected until 30 days after the last dose of PNT2258 for each subject
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea exertional
|
2.2%
1/45 • 24 months
Adverse events were collected until 30 days after the last dose of PNT2258 for each subject
|
|
Vascular disorders
Embolism
|
2.2%
1/45 • 24 months
Adverse events were collected until 30 days after the last dose of PNT2258 for each subject
|
|
Infections and infestations
Escherichia bacteraemia
|
2.2%
1/45 • 24 months
Adverse events were collected until 30 days after the last dose of PNT2258 for each subject
|
|
Injury, poisoning and procedural complications
Foot fracture
|
2.2%
1/45 • 24 months
Adverse events were collected until 30 days after the last dose of PNT2258 for each subject
|
|
Hepatobiliary disorders
Hepatic failure
|
2.2%
1/45 • 24 months
Adverse events were collected until 30 days after the last dose of PNT2258 for each subject
|
|
Metabolism and nutrition disorders
Hypercalcaemia
|
2.2%
1/45 • 24 months
Adverse events were collected until 30 days after the last dose of PNT2258 for each subject
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
2.2%
1/45 • 24 months
Adverse events were collected until 30 days after the last dose of PNT2258 for each subject
|
|
Blood and lymphatic system disorders
Lymphadenopathy
|
2.2%
1/45 • 24 months
Adverse events were collected until 30 days after the last dose of PNT2258 for each subject
|
|
Psychiatric disorders
Mental status changes
|
2.2%
1/45 • 24 months
Adverse events were collected until 30 days after the last dose of PNT2258 for each subject
|
|
Gastrointestinal disorders
Nausea
|
2.2%
1/45 • 24 months
Adverse events were collected until 30 days after the last dose of PNT2258 for each subject
|
|
General disorders
Non-cardiac chest pain
|
2.2%
1/45 • 24 months
Adverse events were collected until 30 days after the last dose of PNT2258 for each subject
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
2.2%
1/45 • 24 months
Adverse events were collected until 30 days after the last dose of PNT2258 for each subject
|
|
Infections and infestations
Septic shock
|
2.2%
1/45 • 24 months
Adverse events were collected until 30 days after the last dose of PNT2258 for each subject
|
|
Nervous system disorders
Spinal cord compression
|
2.2%
1/45 • 24 months
Adverse events were collected until 30 days after the last dose of PNT2258 for each subject
|
|
Injury, poisoning and procedural complications
Spinal fracture
|
2.2%
1/45 • 24 months
Adverse events were collected until 30 days after the last dose of PNT2258 for each subject
|
|
Infections and infestations
Upper respiratory tract infection
|
2.2%
1/45 • 24 months
Adverse events were collected until 30 days after the last dose of PNT2258 for each subject
|
|
Gastrointestinal disorders
Vomiting
|
2.2%
1/45 • 24 months
Adverse events were collected until 30 days after the last dose of PNT2258 for each subject
|
Other adverse events
| Measure |
PNT2258
n=45 participants at risk
PNT2258 was administered at a dose of 120 mg/m2, as a 3 - 4 hour intravenous (IV) infusion on days 1 through 5 of 21-day induction phase cycles (for eight cycles), followed by continuation phase therapy at a dose of 100 mg/m2, as a 2 - 3 hour intravenous (IV) infusion on days 1 through 4 of a 28-day cycle.
|
|---|---|
|
General disorders
Fatigue
|
44.4%
20/45 • 24 months
Adverse events were collected until 30 days after the last dose of PNT2258 for each subject
|
|
Gastrointestinal disorders
Nausea
|
40.0%
18/45 • 24 months
Adverse events were collected until 30 days after the last dose of PNT2258 for each subject
|
|
Gastrointestinal disorders
Diarrhoea
|
40.0%
18/45 • 24 months
Adverse events were collected until 30 days after the last dose of PNT2258 for each subject
|
|
General disorders
Pyrexia
|
28.9%
13/45 • 24 months
Adverse events were collected until 30 days after the last dose of PNT2258 for each subject
|
|
Blood and lymphatic system disorders
Anaemia
|
28.9%
13/45 • 24 months
Adverse events were collected until 30 days after the last dose of PNT2258 for each subject
|
|
Gastrointestinal disorders
Vomiting
|
24.4%
11/45 • 24 months
Adverse events were collected until 30 days after the last dose of PNT2258 for each subject
|
|
Musculoskeletal and connective tissue disorders
Back Pain
|
22.2%
10/45 • 24 months
Adverse events were collected until 30 days after the last dose of PNT2258 for each subject
|
|
Metabolism and nutrition disorders
Decreased appetite
|
24.4%
11/45 • 24 months
Adverse events were collected until 30 days after the last dose of PNT2258 for each subject
|
|
Nervous system disorders
Dizziness
|
24.4%
11/45 • 24 months
Adverse events were collected until 30 days after the last dose of PNT2258 for each subject
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
24.4%
11/45 • 24 months
Adverse events were collected until 30 days after the last dose of PNT2258 for each subject
|
|
Gastrointestinal disorders
Constipation
|
22.2%
10/45 • 24 months
Adverse events were collected until 30 days after the last dose of PNT2258 for each subject
|
|
Investigations
Aspartate aminotransferase increased
|
20.0%
9/45 • 24 months
Adverse events were collected until 30 days after the last dose of PNT2258 for each subject
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
20.0%
9/45 • 24 months
Adverse events were collected until 30 days after the last dose of PNT2258 for each subject
|
|
Vascular disorders
Hypotension
|
17.8%
8/45 • 24 months
Adverse events were collected until 30 days after the last dose of PNT2258 for each subject
|
|
General disorders
Chills
|
17.8%
8/45 • 24 months
Adverse events were collected until 30 days after the last dose of PNT2258 for each subject
|
|
Investigations
Alanine aminotransferase increased
|
17.8%
8/45 • 24 months
Adverse events were collected until 30 days after the last dose of PNT2258 for each subject
|
|
Psychiatric disorders
Insomnia
|
15.6%
7/45 • 24 months
Adverse events were collected until 30 days after the last dose of PNT2258 for each subject
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
15.6%
7/45 • 24 months
Adverse events were collected until 30 days after the last dose of PNT2258 for each subject
|
|
Gastrointestinal disorders
Abdominal pain
|
13.3%
6/45 • 24 months
Adverse events were collected until 30 days after the last dose of PNT2258 for each subject
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
13.3%
6/45 • 24 months
Adverse events were collected until 30 days after the last dose of PNT2258 for each subject
|
|
Nervous system disorders
Hypoaesthesia
|
13.3%
6/45 • 24 months
Adverse events were collected until 30 days after the last dose of PNT2258 for each subject
|
|
Nervous system disorders
Headache
|
11.1%
5/45 • 24 months
Adverse events were collected until 30 days after the last dose of PNT2258 for each subject
|
|
Investigations
Neutrophil count decreased
|
11.1%
5/45 • 24 months
Adverse events were collected until 30 days after the last dose of PNT2258 for each subject
|
|
Investigations
Platelet count decreased
|
11.1%
5/45 • 24 months
Adverse events were collected until 30 days after the last dose of PNT2258 for each subject
|
|
Gastrointestinal disorders
Abdominal distension
|
8.9%
4/45 • 24 months
Adverse events were collected until 30 days after the last dose of PNT2258 for each subject
|
|
Gastrointestinal disorders
Dry mouth
|
8.9%
4/45 • 24 months
Adverse events were collected until 30 days after the last dose of PNT2258 for each subject
|
|
Respiratory, thoracic and mediastinal disorders
Hiccups
|
8.9%
4/45 • 24 months
Adverse events were collected until 30 days after the last dose of PNT2258 for each subject
|
|
Vascular disorders
Hypertension
|
8.9%
4/45 • 24 months
Adverse events were collected until 30 days after the last dose of PNT2258 for each subject
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
8.9%
4/45 • 24 months
Adverse events were collected until 30 days after the last dose of PNT2258 for each subject
|
|
Metabolism and nutrition disorders
Hypophosphataemia
|
8.9%
4/45 • 24 months
Adverse events were collected until 30 days after the last dose of PNT2258 for each subject
|
|
Cardiac disorders
Sinus tachycardia
|
8.9%
4/45 • 24 months
Adverse events were collected until 30 days after the last dose of PNT2258 for each subject
|
|
Investigations
White blood cell count decreased
|
8.9%
4/45 • 24 months
Adverse events were collected until 30 days after the last dose of PNT2258 for each subject
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
6.7%
3/45 • 24 months
Adverse events were collected until 30 days after the last dose of PNT2258 for each subject
|
|
General disorders
Asthenia
|
6.7%
3/45 • 24 months
Adverse events were collected until 30 days after the last dose of PNT2258 for each subject
|
|
Investigations
Blood creatinine increased
|
6.7%
3/45 • 24 months
Adverse events were collected until 30 days after the last dose of PNT2258 for each subject
|
|
Psychiatric disorders
Depression
|
6.7%
3/45 • 24 months
Adverse events were collected until 30 days after the last dose of PNT2258 for each subject
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
6.7%
3/45 • 24 months
Adverse events were collected until 30 days after the last dose of PNT2258 for each subject
|
|
Metabolism and nutrition disorders
Hypercalcaemia
|
6.7%
3/45 • 24 months
Adverse events were collected until 30 days after the last dose of PNT2258 for each subject
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
6.7%
3/45 • 24 months
Adverse events were collected until 30 days after the last dose of PNT2258 for each subject
|
|
General disorders
Influenza like illness
|
6.7%
3/45 • 24 months
Adverse events were collected until 30 days after the last dose of PNT2258 for each subject
|
|
Nervous system disorders
Lethargy
|
6.7%
3/45 • 24 months
Adverse events were collected until 30 days after the last dose of PNT2258 for each subject
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
6.7%
3/45 • 24 months
Adverse events were collected until 30 days after the last dose of PNT2258 for each subject
|
|
Blood and lymphatic system disorders
Neutropenia
|
6.7%
3/45 • 24 months
Adverse events were collected until 30 days after the last dose of PNT2258 for each subject
|
|
Skin and subcutaneous tissue disorders
Night sweats
|
6.7%
3/45 • 24 months
Adverse events were collected until 30 days after the last dose of PNT2258 for each subject
|
|
General disorders
Non-cardiac chest pain
|
6.7%
3/45 • 24 months
Adverse events were collected until 30 days after the last dose of PNT2258 for each subject
|
|
General disorders
Oedema peripheral
|
6.7%
3/45 • 24 months
Adverse events were collected until 30 days after the last dose of PNT2258 for each subject
|
|
Nervous system disorders
Paraesthesia
|
6.7%
3/45 • 24 months
Adverse events were collected until 30 days after the last dose of PNT2258 for each subject
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour pain
|
6.7%
3/45 • 24 months
Adverse events were collected until 30 days after the last dose of PNT2258 for each subject
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place