Trial Outcomes & Findings for Study of Glembatumumab Vedotin in gpNMB-Expressing, Advanced or Metastatic SCC of the Lung (NCT NCT02713828)
NCT ID: NCT02713828
Last Updated: 2019-07-16
Results Overview
To determine the Maximum Tolerated Dose (MTD) by number of participants with DLTs.
Recruitment status
TERMINATED
Study phase
PHASE1/PHASE2
Target enrollment
13 participants
Primary outcome timeframe
42 (±3) days
Results posted on
2019-07-16
Participant Flow
Participant milestones
| Measure |
Phase I: Glembatumumab Vedotin
Glembatumumab vedotin once every three weeks (q3w) by 90-minute intravenous (IV) infusion, until disease progression or intolerance. The Dose-Limiting Toxicity (DLT) evaluation period for determination of the appropriateness of dose-escalation will be through the end of the second treatment cycle.
Phase I: Glembatumumab Vedotin: Escalation Phase: Three to 6 patients will be enrolled in each dose cohort based on a standard Phase I dose escalation scheme. For the dose-escalation, the starting dose of glembatumumab vedotin will be 1.9 mg/kg q3w (Cohort 1). In the event of ≥ 2 DLTs, the dose will de-escalate to Cohort -1 (1.3 mg/kg).
Dose escalation from Cohort 1 to Cohort 2 (2.2 mg/kg) may proceed if three patients in Cohort 1 complete the DLT observation period with 0 DLTs, or if six patients in Cohort 1 complete the DLT observation period with 0 or 1 DLTs.
|
Phase II: Glembatumumab Vedotin
Glembatumumab vedotin once every three weeks (q3w) by 90-minute intravenous (IV) infusion, until disease progression or intolerance. The Maximum Tolerated Dose (MTD) determined in Phase I will be used in Phase II.
Phase II: Glembatumumab Vedotin: In Stage 1, approximately 20 eligible, treated patients will be enrolled. If ≥ 2 patients achieve a tumor response (Partial Response \[PR\] or Complete Response \[CR\]), an additional 15 eligible, treated patients will be enrolled in Stage 2, for a maximum total of 35 eligible, treated patients.
|
|---|---|---|
|
Overall Study
STARTED
|
13
|
0
|
|
Overall Study
COMPLETED
|
8
|
0
|
|
Overall Study
NOT COMPLETED
|
5
|
0
|
Reasons for withdrawal
| Measure |
Phase I: Glembatumumab Vedotin
Glembatumumab vedotin once every three weeks (q3w) by 90-minute intravenous (IV) infusion, until disease progression or intolerance. The Dose-Limiting Toxicity (DLT) evaluation period for determination of the appropriateness of dose-escalation will be through the end of the second treatment cycle.
Phase I: Glembatumumab Vedotin: Escalation Phase: Three to 6 patients will be enrolled in each dose cohort based on a standard Phase I dose escalation scheme. For the dose-escalation, the starting dose of glembatumumab vedotin will be 1.9 mg/kg q3w (Cohort 1). In the event of ≥ 2 DLTs, the dose will de-escalate to Cohort -1 (1.3 mg/kg).
Dose escalation from Cohort 1 to Cohort 2 (2.2 mg/kg) may proceed if three patients in Cohort 1 complete the DLT observation period with 0 DLTs, or if six patients in Cohort 1 complete the DLT observation period with 0 or 1 DLTs.
|
Phase II: Glembatumumab Vedotin
Glembatumumab vedotin once every three weeks (q3w) by 90-minute intravenous (IV) infusion, until disease progression or intolerance. The Maximum Tolerated Dose (MTD) determined in Phase I will be used in Phase II.
Phase II: Glembatumumab Vedotin: In Stage 1, approximately 20 eligible, treated patients will be enrolled. If ≥ 2 patients achieve a tumor response (Partial Response \[PR\] or Complete Response \[CR\]), an additional 15 eligible, treated patients will be enrolled in Stage 2, for a maximum total of 35 eligible, treated patients.
|
|---|---|---|
|
Overall Study
Death
|
2
|
0
|
|
Overall Study
Withdrawal by Subject
|
1
|
0
|
|
Overall Study
study terminated but patient allowed to
|
2
|
0
|
Baseline Characteristics
Study of Glembatumumab Vedotin in gpNMB-Expressing, Advanced or Metastatic SCC of the Lung
Baseline characteristics by cohort
| Measure |
Phase I: Glembatumumab Vedotin
n=13 Participants
Glembatumumab vedotin once every three weeks (q3w) by 90-minute intravenous (IV) infusion, until disease progression or intolerance. The Dose-Limiting Toxicity (DLT) evaluation period for determination of the appropriateness of dose-escalation will be through the end of the second treatment cycle.
Phase I: Glembatumumab Vedotin: Escalation Phase: Three to 6 patients will be enrolled in each dose cohort based on a standard Phase I dose escalation scheme. For the dose-escalation, the starting dose of glembatumumab vedotin will be 1.9 mg/kg q3w (Cohort 1). In the event of ≥ 2 DLTs, the dose will de-escalate to Cohort -1 (1.3 mg/kg).
Dose escalation from Cohort 1 to Cohort 2 (2.2 mg/kg) may proceed if three patients in Cohort 1 complete the DLT observation period with 0 DLTs, or if six patients in Cohort 1 complete the DLT observation period with 0 or 1 DLTs.
|
Phase II: Glembatumumab Vedotin
Glembatumumab vedotin once every three weeks (q3w) by 90-minute intravenous (IV) infusion, until disease progression or intolerance. The Maximum Tolerated Dose (MTD) determined in Phase I will be used in Phase II.
Phase II: Glembatumumab Vedotin: In Stage 1, approximately 20 eligible, treated patients will be enrolled. If ≥ 2 patients achieve a tumor response (Partial Response \[PR\] or Complete Response \[CR\]), an additional 15 eligible, treated patients will be enrolled in Stage 2, for a maximum total of 35 eligible, treated patients.
|
Total
n=13 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
63 years
n=5 Participants
|
—
|
63 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
6 Participants
n=5 Participants
|
—
|
6 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
7 Participants
n=5 Participants
|
—
|
7 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
—
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=5 Participants
|
—
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
—
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
—
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
11 Participants
n=5 Participants
|
—
|
11 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
—
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=5 Participants
|
—
|
1 Participants
n=5 Participants
|
|
ECOG Performance Status
PS 0
|
2 Participants
n=5 Participants
|
—
|
2 Participants
n=5 Participants
|
|
ECOG Performance Status
PS 1
|
11 Participants
n=5 Participants
|
—
|
11 Participants
n=5 Participants
|
|
Prior lines of treatment
1
|
5 Participants
n=5 Participants
|
—
|
5 Participants
n=5 Participants
|
|
Prior lines of treatment
2
|
4 Participants
n=5 Participants
|
—
|
4 Participants
n=5 Participants
|
|
Prior lines of treatment
>=3
|
3 Participants
n=5 Participants
|
—
|
3 Participants
n=5 Participants
|
|
Prior lines of treatment
unknown
|
1 Participants
n=5 Participants
|
—
|
1 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 42 (±3) daysTo determine the Maximum Tolerated Dose (MTD) by number of participants with DLTs.
Outcome measures
| Measure |
Phase I: Glembatumumab Vedotin
n=13 Participants
Glembatumumab vedotin once every three weeks (q3w) by 90-minute intravenous (IV) infusion, until disease progression or intolerance. The Dose-Limiting Toxicity (DLT) evaluation period for determination of the appropriateness of dose-escalation will be through the end of the second treatment cycle.
Phase I: Glembatumumab Vedotin: Escalation Phase: Three to 6 patients will be enrolled in each dose cohort based on a standard Phase I dose escalation scheme. For the dose-escalation, the starting dose of glembatumumab vedotin will be 1.9 mg/kg q3w (Cohort 1). In the event of ≥ 2 DLTs, the dose will de-escalate to Cohort -1 (1.3 mg/kg).
Dose escalation from Cohort 1 to Cohort 2 (2.2 mg/kg) may proceed if three patients in Cohort 1 complete the DLT observation period with 0 DLTs, or if six patients in Cohort 1 complete the DLT observation period with 0 or 1 DLTs.
|
|---|---|
|
Phase I: Determine Maximum Tolerated Dose (MTD)
|
NA mg/kg
PrECOG received notification from Celldex noting the suspension of glembatumumab vedotin development and the closure of the PrE0504 study before the MTD was determined and the phase I part of the study was completed.
|
PRIMARY outcome
Timeframe: 40 monthsPopulation: The study terminated early during the phase I portion of the trial
Determine the anti-tumor activity, as assessed by ORR in accordance with RECIST 1.1, of the MTD of glembatumumab vedotin in patients with advanced gpNMB-expressing SCC of the lung.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: 23 monthsTo further characterize the safety of glembatumumab vedotin by the number of participants with abnormal laboratory values and/or adverse events related to treatment (including Serious Adverse Events and Other Adverse Events).
Outcome measures
| Measure |
Phase I: Glembatumumab Vedotin
n=13 Participants
Glembatumumab vedotin once every three weeks (q3w) by 90-minute intravenous (IV) infusion, until disease progression or intolerance. The Dose-Limiting Toxicity (DLT) evaluation period for determination of the appropriateness of dose-escalation will be through the end of the second treatment cycle.
Phase I: Glembatumumab Vedotin: Escalation Phase: Three to 6 patients will be enrolled in each dose cohort based on a standard Phase I dose escalation scheme. For the dose-escalation, the starting dose of glembatumumab vedotin will be 1.9 mg/kg q3w (Cohort 1). In the event of ≥ 2 DLTs, the dose will de-escalate to Cohort -1 (1.3 mg/kg).
Dose escalation from Cohort 1 to Cohort 2 (2.2 mg/kg) may proceed if three patients in Cohort 1 complete the DLT observation period with 0 DLTs, or if six patients in Cohort 1 complete the DLT observation period with 0 or 1 DLTs.
|
|---|---|
|
Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0.
|
13 Participants
|
SECONDARY outcome
Timeframe: 23 monthsPopulation: 1 patient achieved partial response. The duration of this patient's response is at least 9.4 months, with response ongoing at the time of final report.
DOR assessed in accordance with RECIST 1.1.
Outcome measures
| Measure |
Phase I: Glembatumumab Vedotin
n=1 Participants
Glembatumumab vedotin once every three weeks (q3w) by 90-minute intravenous (IV) infusion, until disease progression or intolerance. The Dose-Limiting Toxicity (DLT) evaluation period for determination of the appropriateness of dose-escalation will be through the end of the second treatment cycle.
Phase I: Glembatumumab Vedotin: Escalation Phase: Three to 6 patients will be enrolled in each dose cohort based on a standard Phase I dose escalation scheme. For the dose-escalation, the starting dose of glembatumumab vedotin will be 1.9 mg/kg q3w (Cohort 1). In the event of ≥ 2 DLTs, the dose will de-escalate to Cohort -1 (1.3 mg/kg).
Dose escalation from Cohort 1 to Cohort 2 (2.2 mg/kg) may proceed if three patients in Cohort 1 complete the DLT observation period with 0 DLTs, or if six patients in Cohort 1 complete the DLT observation period with 0 or 1 DLTs.
|
|---|---|
|
Duration of Objective Response (DOR)
|
9.4 months
|
SECONDARY outcome
Timeframe: 23 monthsPFS assessed in accordance with RECIST 1.1.
Outcome measures
| Measure |
Phase I: Glembatumumab Vedotin
n=13 Participants
Glembatumumab vedotin once every three weeks (q3w) by 90-minute intravenous (IV) infusion, until disease progression or intolerance. The Dose-Limiting Toxicity (DLT) evaluation period for determination of the appropriateness of dose-escalation will be through the end of the second treatment cycle.
Phase I: Glembatumumab Vedotin: Escalation Phase: Three to 6 patients will be enrolled in each dose cohort based on a standard Phase I dose escalation scheme. For the dose-escalation, the starting dose of glembatumumab vedotin will be 1.9 mg/kg q3w (Cohort 1). In the event of ≥ 2 DLTs, the dose will de-escalate to Cohort -1 (1.3 mg/kg).
Dose escalation from Cohort 1 to Cohort 2 (2.2 mg/kg) may proceed if three patients in Cohort 1 complete the DLT observation period with 0 DLTs, or if six patients in Cohort 1 complete the DLT observation period with 0 or 1 DLTs.
|
|---|---|
|
Progression-Free Survival (PFS)
|
2.5 months
Interval 1.6 to
Upper limit can't be estimated.
|
SECONDARY outcome
Timeframe: 23 monthsOS assessed in accordance with RECIST 1.1.
Outcome measures
| Measure |
Phase I: Glembatumumab Vedotin
n=13 Participants
Glembatumumab vedotin once every three weeks (q3w) by 90-minute intravenous (IV) infusion, until disease progression or intolerance. The Dose-Limiting Toxicity (DLT) evaluation period for determination of the appropriateness of dose-escalation will be through the end of the second treatment cycle.
Phase I: Glembatumumab Vedotin: Escalation Phase: Three to 6 patients will be enrolled in each dose cohort based on a standard Phase I dose escalation scheme. For the dose-escalation, the starting dose of glembatumumab vedotin will be 1.9 mg/kg q3w (Cohort 1). In the event of ≥ 2 DLTs, the dose will de-escalate to Cohort -1 (1.3 mg/kg).
Dose escalation from Cohort 1 to Cohort 2 (2.2 mg/kg) may proceed if three patients in Cohort 1 complete the DLT observation period with 0 DLTs, or if six patients in Cohort 1 complete the DLT observation period with 0 or 1 DLTs.
|
|---|---|
|
Overall Survival (OS)
|
5.8 months
Interval 2.5 to
Upper limit can't be estimated
|
Adverse Events
Phase I: Glembatumumab Vedotin
Serious events: 9 serious events
Other events: 8 other events
Deaths: 7 deaths
Serious adverse events
| Measure |
Phase I: Glembatumumab Vedotin
n=13 participants at risk
Glembatumumab vedotin once every three weeks (q3w) by 90-minute intravenous (IV) infusion, until disease progression or intolerance. The Dose-Limiting Toxicity (DLT) evaluation period for determination of the appropriateness of dose-escalation will be through the end of the second treatment cycle.
Phase I: Glembatumumab Vedotin: Escalation Phase: Three to 6 patients will be enrolled in each dose cohort based on a standard Phase I dose escalation scheme. For the dose-escalation, the starting dose of glembatumumab vedotin will be 1.9 mg/kg q3w (Cohort 1). In the event of ≥ 2 DLTs, the dose will de-escalate to Cohort -1 (1.3 mg/kg).
Dose escalation from Cohort 1 to Cohort 2 (2.2 mg/kg) may proceed if three patients in Cohort 1 complete the DLT observation period with 0 DLTs, or if six patients in Cohort 1 complete the DLT observation period with 0 or 1 DLTs.
|
|---|---|
|
Gastrointestinal disorders
Abdominal pain
|
7.7%
1/13 • 23 months
|
|
General disorders
Disease progression
|
7.7%
1/13 • 23 months
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
15.4%
2/13 • 23 months
|
|
Metabolism and nutrition disorders
Hypercalcaemia
|
7.7%
1/13 • 23 months
|
|
Blood and lymphatic system disorders
Neutropenia
|
7.7%
1/13 • 23 months
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
7.7%
1/13 • 23 months
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
15.4%
2/13 • 23 months
|
|
Infections and infestations
Urinary tract infection
|
7.7%
1/13 • 23 months
|
Other adverse events
| Measure |
Phase I: Glembatumumab Vedotin
n=13 participants at risk
Glembatumumab vedotin once every three weeks (q3w) by 90-minute intravenous (IV) infusion, until disease progression or intolerance. The Dose-Limiting Toxicity (DLT) evaluation period for determination of the appropriateness of dose-escalation will be through the end of the second treatment cycle.
Phase I: Glembatumumab Vedotin: Escalation Phase: Three to 6 patients will be enrolled in each dose cohort based on a standard Phase I dose escalation scheme. For the dose-escalation, the starting dose of glembatumumab vedotin will be 1.9 mg/kg q3w (Cohort 1). In the event of ≥ 2 DLTs, the dose will de-escalate to Cohort -1 (1.3 mg/kg).
Dose escalation from Cohort 1 to Cohort 2 (2.2 mg/kg) may proceed if three patients in Cohort 1 complete the DLT observation period with 0 DLTs, or if six patients in Cohort 1 complete the DLT observation period with 0 or 1 DLTs.
|
|---|---|
|
Gastrointestinal disorders
Abdominal pain
|
7.7%
1/13 • 23 months
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
7.7%
1/13 • 23 months
|
|
Metabolism and nutrition disorders
Metabolism and nutrition disorders Dehydration
|
7.7%
1/13 • 23 months
|
|
Gastrointestinal disorders
Dry mouth
|
7.7%
1/13 • 23 months
|
|
Nervous system disorders
Dysgeusia
|
7.7%
1/13 • 23 months
|
|
Blood and lymphatic system disorders
Neutropenia
|
7.7%
1/13 • 23 months
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
7.7%
1/13 • 23 months
|
|
Skin and subcutaneous tissue disorders
Rash papular
|
7.7%
1/13 • 23 months
|
|
Investigations
Alanine aminotransferase increased
|
15.4%
2/13 • 23 months
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
7.7%
1/13 • 23 months
|
|
Blood and lymphatic system disorders
Anaemia
|
15.4%
2/13 • 23 months
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
7.7%
1/13 • 23 months
|
|
Investigations
Aspartate aminotransferase increased
|
7.7%
1/13 • 23 months
|
|
Infections and infestations
Candida infection
|
7.7%
1/13 • 23 months
|
|
Metabolism and nutrition disorders
Decreased appetite
|
23.1%
3/13 • 23 months
|
|
Gastrointestinal disorders
Diarrhoea
|
15.4%
2/13 • 23 months
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
7.7%
1/13 • 23 months
|
|
Skin and subcutaneous tissue disorders
Erythema
|
7.7%
1/13 • 23 months
|
|
Eye disorders
Eye pain
|
7.7%
1/13 • 23 months
|
|
General disorders
Fatigue
|
23.1%
3/13 • 23 months
|
|
Gastrointestinal disorders
Hypoaesthesia oral
|
7.7%
1/13 • 23 months
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
7.7%
1/13 • 23 months
|
|
Metabolism and nutrition disorders
Hypomagnesaemia
|
7.7%
1/13 • 23 months
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
7.7%
1/13 • 23 months
|
|
Metabolism and nutrition disorders
Hypophosphataemia
|
7.7%
1/13 • 23 months
|
|
Psychiatric disorders
Insomnia
|
7.7%
1/13 • 23 months
|
|
Eye disorders
Iridocyclitis
|
7.7%
1/13 • 23 months
|
|
Blood and lymphatic system disorders
Leukopenia
|
7.7%
1/13 • 23 months
|
|
Investigations
Lymphocyte count decreased
|
7.7%
1/13 • 23 months
|
|
General disorders
Malaise
|
7.7%
1/13 • 23 months
|
|
Musculoskeletal and connective tissue disorders
Muscular weakness
|
7.7%
1/13 • 23 months
|
|
Gastrointestinal disorders
Nausea
|
7.7%
1/13 • 23 months
|
|
Nervous system disorders
Neuropathy peripheral
|
7.7%
1/13 • 23 months
|
|
Investigations
Platelet count decreased
|
7.7%
1/13 • 23 months
|
|
Skin and subcutaneous tissue disorders
Rash
|
7.7%
1/13 • 23 months
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
7.7%
1/13 • 23 months
|
|
Gastrointestinal disorders
Stomatitis
|
7.7%
1/13 • 23 months
|
|
Investigations
Weight decreased
|
7.7%
1/13 • 23 months
|
|
Investigations
White blood cell count decreased
|
7.7%
1/13 • 23 months
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place