Advanced Solid Tumors
Conditions
Brief summary
The study determined the recommended Phase 2 loading and maintenance doses and dose schedules for administering dalotuzumab using dose-limiting toxicities (DLTs) observed during the entire treatment period (Up to 18 months). The primary hypothesis of the study was that administration of dalotuzumab as an every other week infusion in participants with relapsed or refractory locally advanced or metastatic cancers associated with a high frequency of insulin-like growth factor receptor type 1(IGF-1R) overexpression will be generally safe and well tolerated to permit further study and achieve a constant clearance and a minimum trough concentration of 3 µg/mL.
Detailed description
The study consisted of 3 parts. In Part 1 the loading dose was escalated while the maintenance dose was kept constant. In Part 2 the loading dose was kept constant while the maintenance dose was escalated. In Part 3 the recommended phase 2 loading and maintenance doses and schedule were administered to an expanded cohort to explore safety and efficacy of dalotuzumab.
Interventions
DRUGdalotuzumab
Administered as an IV infusion over one to two hours
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Males and females with advanced solid tumors who have failed to respond to standard therapy, ages 18 years and older, with adequate organ function
Exclusion criteria
* Participant is using growth hormones or growth hormone inhibitors * Participant is known to be allergic to components of the drug or similar drugs (e.g. monoclonal antibodies such as rituximab or biological therapies such as immunoglobulin G * Participant has had chemotherapy, radiotherapy, or biological therapy within 4-6 weeks of entering the study or has not recovered from previous therapy * Participant is taking part in or has taken part in a study of an investigational compound or device within 30 days of their first dose of study drug * Participant has an active Central Nervous System metastases and/or carcinomatous meningitis. However, a participant who has completed a course of therapy and is clinically stable may be able to participate * Participant is pregnant or breastfeeding * Participant is human immunodeficiency virus (HIV) positive * Participant has a history of Hepatitis B or C * Participant has symptomatic ascites or pleural effusion. However, if the participant has received treatment and is stable, they may be able to participate * Female participant plans to become pregnant or a male participant who plans to impregnate their partner during the time the study is ongoing
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Steady-state Serum Concentration of Dalotuzumab at 336 Hours (C336) After the First Maintenance Dose | 2 weeks post first maintenance dose of study drug (3 weeks post loading dose of study drug) | Blood samples were obtained for analysis of steady-state serum concentration of dalotuzumab at 336 hours (C336) after the first maintenance dose of dalotuzumab. The C336 of dalotuzumab after intravenous administration is presented. |
| Number of Participants Who Experience One or More Dose- Limiting Toxicities (DLTs) | The entire treatment period (Up to 18 months) | Dose-limiting toxicities (DLT) were assessed and graded using the National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE). A DLT was defined as the occurrence of any of the following events, that were judged by the study investigator, to be related to the study medication: Grade 4 neutropenia; Grade 3 neutropenia with fever \>38.5 degrees Celsius; Grade 4 thrombocytopenia; Grade 3 or Grade 4 non-hematologic toxicity (except alopecia and inadequately treated diarrhea, nausea, and vomiting, and hyperglycemia lasting less than 5 days; and Grade 3 or greater hyperglycemia lasting for more than 5 days in spite of optimal medical management. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With a Positive Human-anti-humanized-antibody (HAHA) Titer | Prior to second and subsequent doses of study drug (Up to 1 year post-first dose) | The formation of HAHAs may block efficacy by prematurely clearing dalotuzumab and limit the possibility of future dalotuzumab therapy. Blood samples for the measurement of serum levels of HAHAs were obtained prior to treatment with dalotuzumab, and pre-dose Week 3, Week 5, pre-dose every 8 subsequent weeks, and end of treatment (post-study: 4 weeks after last dose of study drug). Positive HAHA status for a participant is defined as testing positive on both the screening and immunodepletion assays at one or more visits. |
| Percent Change From Baseline in Serum IGF-1R Protein Level at Week 5 | Baseline and Week 5 | IGF-1R expression was measured in pre- and post-dose biopsy samples using immunohistochemistry (IHC) and enzyme-linked immunosorbent assay (ELISA) assays. Results were expressed as a percent change from baseline in IG1-FR expression for participants pooled across all dose arms in the study and calculated by study week. A post-dose decrease in IGF-1R expression was an indication of target engagement by dalotuzumab. A larger percent change correlated with a greater target engagement. |
| Percent Change From Baseline in Serum IGF-1R Protein Level at Week 9 | Baseline and Week 9 | IGF-1R expression was measured in pre- and post-dose biopsy samples using immunohistochemistry (IHC) and enzyme-linked immunosorbent assay (ELISA) assays. Results were expressed as a percent change from baseline in IG1-FR expression for participants pooled across all dose arms in the study and calculated by study week. A post-dose decrease in IGF-1R expression was an indication of target engagement by dalotuzumab. A larger percent change correlated with a greater target engagement. |
| Percent Change From Baseline in Serum IGF-1R Protein Level at Week 13 | Baseline and Week 13 | IGF-1R expression was measured in pre- and post-dose biopsy samples using immunohistochemistry (IHC) and enzyme-linked immunosorbent assay (ELISA) assays. Results were expressed as a percent change from baseline in IG1-FR expression for participants pooled across all dose arms in the study and calculated by study week. A post-dose decrease in IGF-1R expression was an indication of target engagement by dalotuzumab. A larger percent change correlated with a greater target engagement. |
| Percent Change From Baseline in Serum IGF-1R Protein Level at Week 17 | Baseline and Week 17 | IGF-1R expression was measured in pre- and post-dose biopsy samples using immunohistochemistry (IHC) and enzyme-linked immunosorbent assay (ELISA) assays. Results were expressed as a percent change from baseline in IG1-FR expression for participants pooled across all dose arms in the study and calculated by study week. A post-dose decrease in IGF-1R expression was an indication of target engagement by dalotuzumab. A larger percent change correlated with a greater target engagement. |
| Percent Change From Baseline in Serum IGF-1R Protein Level at Week 21 | Baseline and Week 21 | IGF-1R expression was measured in pre- and post-dose biopsy samples using immunohistochemistry (IHC) and enzyme-linked immunosorbent assay (ELISA) assays. Results were expressed as a percent change from baseline in IG1-FR expression for participants pooled across all dose arms in the study and calculated by study week. A post-dose decrease in IGF-1R expression was an indication of target engagement by dalotuzumab. A larger percent change correlated with a greater target engagement. |
| Percent Change From Baseline in Serum IGF-1R Protein Level at Week 25 | Baseline and Week 25 | IGF-1R expression was measured in pre- and post-dose biopsy samples using immunohistochemistry (IHC) and enzyme-linked immunosorbent assay (ELISA) assays. Results were expressed as a percent change from baseline in IG1-FR expression for participants pooled across all dose arms in the study and calculated by study week. A post-dose decrease in IGF-1R expression was an indication of target engagement by dalotuzumab. A larger percent change correlated with a greater target engagement. |
| Number of Participants Who Experienced a Complete Response (CR) or Partial Response (PR) | Up to 18 months post first dose of study drug | Complete Response (disappearance of all target lesions) or Partial Response (at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters) using Response Criteria in Solid Tumors (RECIST). Tumor response was assessed prior to first dose and every 8 weeks beginning pre-dose of Week 9 for up to 18 months. The best response out of all measurements for each participant was used for determining CR and PR. |
| Percent Change From Baseline in Serum IGF-1R Protein Level at Week 33 | Baseline and Week 33 | IGF-1R expression was measured in pre- and post-dose biopsy samples using immunohistochemistry (IHC) and enzyme-linked immunosorbent assay (ELISA) assays. Results were expressed as a percent change from baseline in IG1-FR expression for participants pooled across all dose arms in the study and calculated by study week. A post-dose decrease in IGF-1R expression was an indication of target engagement by dalotuzumab. A larger percent change correlated with a greater target engagement. |
| Percent Change From Baseline in Serum IGF-1R Protein Level at Week 37 | Baseline and Week 37 | IGF-1R expression was measured in pre- and post-dose biopsy samples using immunohistochemistry (IHC) and enzyme-linked immunosorbent assay (ELISA) assays. Results were expressed as a percent change from baseline in IG1-FR expression for participants pooled across all dose arms in the study and calculated by study week. A post-dose decrease in IGF-1R expression was an indication of target engagement by dalotuzumab. A larger percent change correlated with a greater target engagement. |
| Percent Change From Baseline in Serum IGF-1R Protein Level at Week 41 | Baseline and Week 41 | IGF-1R expression was measured in pre- and post-dose biopsy samples using immunohistochemistry (IHC) and enzyme-linked immunosorbent assay (ELISA) assays. Results were expressed as a percent change from baseline in IG1-FR expression for participants pooled across all dose arms in the study and calculated by study week. A post-dose decrease in IGF-1R expression was an indication of target engagement by dalotuzumab. A larger percent change correlated with a greater target engagement. |
| Percent Change From Baseline in Serum IGF-1R Protein Level at Week 45 | Baseline and Week 45 | IGF-1R expression was measured in pre- and post-dose biopsy samples using immunohistochemistry (IHC) and enzyme-linked immunosorbent assay (ELISA) assays. Results were expressed as a percent change from baseline in IG1-FR expression for participants pooled across all dose arms in the study and calculated by study week. A post-dose decrease in IGF-1R expression was an indication of target engagement by dalotuzumab. A larger percent change correlated with a greater target engagement. |
| Percent Change From Baseline in Serum IGF-1R Protein Level at Week 53 | Baseline and Week 53 | IGF-1R expression was measured in pre- and post-dose biopsy samples using immunohistochemistry (IHC) and enzyme-linked immunosorbent assay (ELISA) assays. Results were expressed as a percent change from baseline in IG1-FR expression for participants pooled across all dose arms in the study and calculated by study week. A post-dose decrease in IGF-1R expression was an indication of target engagement by dalotuzumab. A larger percent change correlated with a greater target engagement. |
| Percent Change From Baseline in Serum IGF-1R Protein Level at Week 49 | Baseline and Week 49 | IGF-1R expression was measured in pre- and post-dose biopsy samples using immunohistochemistry (IHC) and enzyme-linked immunosorbent assay (ELISA) assays. Results were expressed as a percent change from baseline in IG1-FR expression for participants pooled across all dose arms in the study and calculated by study week. A post-dose decrease in IGF-1R expression was an indication of target engagement by dalotuzumab. A larger percent change correlated with a greater target engagement. |
| Percent Change From Baseline in Serum IGF-1R Protein Level at Week 29 | Baseline and Week 29 | IGF-1R expression was measured in pre- and post-dose biopsy samples using immunohistochemistry (IHC) and enzyme-linked immunosorbent assay (ELISA) assays. Results were expressed as a percent change from baseline in IG1-FR expression for participants pooled across all dose arms in the study and calculated by study week. A post-dose decrease in IGF-1R expression was an indication of target engagement by dalotuzumab. A larger percent change correlated with a greater target engagement. |
| Percent Change From Baseline in Serum Insulin-like Growth Factor Receptor Type 1 (IGF-1R) Protein Level at Week 1 | Baseline and Week 1 | IGF-1R expression was measured in pre- and post-dose biopsy samples using immunohistochemistry (IHC) and enzyme-linked immunosorbent assay (ELISA) assays. Results were expressed as a percent change from baseline in IG1-FR expression for participants pooled across all dose arms in the study and calculated by study week. A post-dose decrease in IGF-1R expression was an indication of target engagement by dalotuzumab. A larger percent change correlated with a greater target engagement. |
Participant flow
Recruitment details
This study enrolled participants with metastatic or locally advanced solid tumors, associated with insulin-like growth factor receptor type 1 (IGF-1R) protein expression, that have failed to respond to standard therapy, progressed despite standard therapy, or for which standard therapy does not exist. Other inclusion/exclusion criteria applied.
Participants by arm
| Arm | Count |
|---|---|
| Dalotuzumab 2.5 mg/kg / Dalotuzumab 2.5 mg/kg Participants received a loading dose of dalotuzumab 2.5 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 2.5 mg/kg administered by IV infusion every two weeks for up to 18 months. | 1 |
| Dalotuzumab 5.0 mg/kg / Dalotuzumab 5.0 mg/kg Participants received a loading dose of dalotuzumab 5.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 5.0 mg/kg administered by IV infusion every two weeks for up to 18 months. | 3 |
| Dalotuzumab 10.0 mg/kg / Dalotuzumab 5.0 mg/kg Participants received a loading dose of dalotuzumab 10.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 5.0 mg/kg administered by IV infusion every two weeks for up to 18 months. | 3 |
| Dalotuzumab 15.0 mg/kg / Dalotuzumab 5.0 mg/kg Participants received a loading dose of dalotuzumab 15.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 5.0 mg/kg administered by IV infusion every two weeks for up to 18 months. | 8 |
| Dalotuzumab 20.0 mg/kg / Dalotuzumab 5.0 mg/kg Participants received a loading dose of dalotuzumab 20.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 5.0 mg/kg administered by IV infusion every two weeks for up to 18 months. | 8 |
| Dalotuzumab 15.0 mg/kg / Dalotuzumab 10.0 mg/kg Participants received a loading dose of dalotuzumab 15.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 10.0 mg/kg administered by IV infusion every two weeks for up to 18 months. | 21 |
| Dalotuzumab 15.0 mg/kg / Dalotuzumab 15.0 mg/kg Participants received a loading dose of dalotuzumab 15.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 15.0 mg/kg administered by IV infusion every two weeks for up to 18 months. | 6 |
| Total | 50 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 |
|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 | 0 | 3 | 3 | 6 | 1 |
| Overall Study | Progressive disease | 0 | 3 | 3 | 4 | 5 | 14 | 4 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 1 | 0 | 1 | 1 |
Baseline characteristics
| Characteristic | Dalotuzumab 5.0 mg/kg / Dalotuzumab 5.0 mg/kg | Total | Dalotuzumab 15.0 mg/kg / Dalotuzumab 15.0 mg/kg | Dalotuzumab 15.0 mg/kg / Dalotuzumab 10.0 mg/kg | Dalotuzumab 2.5 mg/kg / Dalotuzumab 2.5 mg/kg | Dalotuzumab 20.0 mg/kg / Dalotuzumab 5.0 mg/kg | Dalotuzumab 15.0 mg/kg / Dalotuzumab 5.0 mg/kg | Dalotuzumab 10.0 mg/kg / Dalotuzumab 5.0 mg/kg |
|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 74.3 Years STANDARD_DEVIATION 9.9 | 61.0 Years STANDARD_DEVIATION 12.7 | 53.7 Years STANDARD_DEVIATION 21.2 | 58.1 Years STANDARD_DEVIATION 11.8 | 62.0 Years | 59.1 Years STANDARD_DEVIATION 7.6 | 71.3 Years STANDARD_DEVIATION 6.5 | 60.3 Years STANDARD_DEVIATION 8.6 |
| Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) ECOG PS = 0 | 1 Participants | 20 Participants | 4 Participants | 10 Participants | 0 Participants | 3 Participants | 1 Participants | 1 Participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) ECOG PS = 1 | 2 Participants | 26 Participants | 1 Participants | 10 Participants | 0 Participants | 5 Participants | 6 Participants | 2 Participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) ECOG PS = 2 | 0 Participants | 4 Participants | 1 Participants | 1 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants |
| Number of Prior Chemotherapy Regimens | 2.7 Regimens STANDARD_DEVIATION 0.6 | 2.9 Regimens STANDARD_DEVIATION 0.4 | 2.5 Regimens STANDARD_DEVIATION 0.8 | 2.9 Regimens STANDARD_DEVIATION 0.3 | 3.0 Regimens | 3.0 Regimens STANDARD_DEVIATION 0 | 3.0 Regimens STANDARD_DEVIATION 0 | 3.0 Regimens STANDARD_DEVIATION 0 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 4 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 7 Participants | 1 Participants | 2 Participants | 0 Participants | 3 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) White | 3 Participants | 38 Participants | 5 Participants | 17 Participants | 1 Participants | 4 Participants | 6 Participants | 2 Participants |
| Sex: Female, Male Female | 1 Participants | 17 Participants | 2 Participants | 10 Participants | 0 Participants | 1 Participants | 1 Participants | 2 Participants |
| Sex: Female, Male Male | 2 Participants | 33 Participants | 4 Participants | 11 Participants | 1 Participants | 7 Participants | 7 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 1 | 1 / 3 | 0 / 3 | 1 / 8 | 1 / 8 | 1 / 21 | 1 / 6 |
| other Total, other adverse events | 1 / 1 | 3 / 3 | 3 / 3 | 8 / 8 | 8 / 8 | 21 / 21 | 6 / 6 |
| serious Total, serious adverse events | 1 / 1 | 2 / 3 | 2 / 3 | 5 / 8 | 6 / 8 | 9 / 21 | 3 / 6 |
Outcome results
Primary
Number of Participants Who Experience One or More Dose- Limiting Toxicities (DLTs)
Dose-limiting toxicities (DLT) were assessed and graded using the National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE). A DLT was defined as the occurrence of any of the following events, that were judged by the study investigator, to be related to the study medication: Grade 4 neutropenia; Grade 3 neutropenia with fever \>38.5 degrees Celsius; Grade 4 thrombocytopenia; Grade 3 or Grade 4 non-hematologic toxicity (except alopecia and inadequately treated diarrhea, nausea, and vomiting, and hyperglycemia lasting less than 5 days; and Grade 3 or greater hyperglycemia lasting for more than 5 days in spite of optimal medical management.
Time frame: The entire treatment period (Up to 18 months)
Population: All participants who received at least one dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Dalotuzumab 2.5 mg/kg / Dalotuzumab 2.5 mg/kg | Number of Participants Who Experience One or More Dose- Limiting Toxicities (DLTs) | 0 Participants |
| Dalotuzumab 5.0 mg/kg / Dalotuzumab 5.0 mg/kg | Number of Participants Who Experience One or More Dose- Limiting Toxicities (DLTs) | 0 Participants |
| Dalotuzumab 10.0 mg/kg / Dalotuzumab 5.0 mg/kg | Number of Participants Who Experience One or More Dose- Limiting Toxicities (DLTs) | 0 Participants |
| Dalotuzumab 15.0 mg/kg / Dalotuzumab 5.0 mg/kg | Number of Participants Who Experience One or More Dose- Limiting Toxicities (DLTs) | 0 Participants |
| Dalotuzumab 20.0 mg/kg / Dalotuzumab 5.0 mg/kg | Number of Participants Who Experience One or More Dose- Limiting Toxicities (DLTs) | 0 Participants |
| Dalotuzumab 15.0 mg/kg / Dalotuzumab 10.0 mg/kg | Number of Participants Who Experience One or More Dose- Limiting Toxicities (DLTs) | 0 Participants |
| Dalotuzumab 15.0 mg/kg / Dalotuzumab 15.0 mg/kg | Number of Participants Who Experience One or More Dose- Limiting Toxicities (DLTs) | 1 Participants |
Primary
Steady-state Serum Concentration of Dalotuzumab at 336 Hours (C336) After the First Maintenance Dose
Blood samples were obtained for analysis of steady-state serum concentration of dalotuzumab at 336 hours (C336) after the first maintenance dose of dalotuzumab. The C336 of dalotuzumab after intravenous administration is presented.
Time frame: 2 weeks post first maintenance dose of study drug (3 weeks post loading dose of study drug)
Population: All participants who received dalotuzumab and had blood samples drawn for pharmacokinetic (PK) analyses.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dalotuzumab 2.5 mg/kg / Dalotuzumab 2.5 mg/kg | Steady-state Serum Concentration of Dalotuzumab at 336 Hours (C336) After the First Maintenance Dose | 4.78 μg/mL | — |
| Dalotuzumab 5.0 mg/kg / Dalotuzumab 5.0 mg/kg | Steady-state Serum Concentration of Dalotuzumab at 336 Hours (C336) After the First Maintenance Dose | 7.48 μg/mL | Standard Deviation 8.5 |
| Dalotuzumab 10.0 mg/kg / Dalotuzumab 5.0 mg/kg | Steady-state Serum Concentration of Dalotuzumab at 336 Hours (C336) After the First Maintenance Dose | 54.57 μg/mL | Standard Deviation 24.64 |
| Dalotuzumab 15.0 mg/kg / Dalotuzumab 5.0 mg/kg | Steady-state Serum Concentration of Dalotuzumab at 336 Hours (C336) After the First Maintenance Dose | 33.00 μg/mL | Standard Deviation 24.9 |
| Dalotuzumab 20.0 mg/kg / Dalotuzumab 5.0 mg/kg | Steady-state Serum Concentration of Dalotuzumab at 336 Hours (C336) After the First Maintenance Dose | 25.95 μg/mL | Standard Deviation 26.22 |
| Dalotuzumab 15.0 mg/kg / Dalotuzumab 10.0 mg/kg | Steady-state Serum Concentration of Dalotuzumab at 336 Hours (C336) After the First Maintenance Dose | 24.39 μg/mL | Standard Deviation 27.63 |
| Dalotuzumab 15.0 mg/kg / Dalotuzumab 15.0 mg/kg | Steady-state Serum Concentration of Dalotuzumab at 336 Hours (C336) After the First Maintenance Dose | 86.73 μg/mL | Standard Deviation 44.56 |
Secondary
Number of Participants Who Experienced a Complete Response (CR) or Partial Response (PR)
Complete Response (disappearance of all target lesions) or Partial Response (at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters) using Response Criteria in Solid Tumors (RECIST). Tumor response was assessed prior to first dose and every 8 weeks beginning pre-dose of Week 9 for up to 18 months. The best response out of all measurements for each participant was used for determining CR and PR.
Time frame: Up to 18 months post first dose of study drug
Population: All participants who received at least one dose of study therapy.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Dalotuzumab 2.5 mg/kg / Dalotuzumab 2.5 mg/kg | Number of Participants Who Experienced a Complete Response (CR) or Partial Response (PR) | 0 Participants |
| Dalotuzumab 5.0 mg/kg / Dalotuzumab 5.0 mg/kg | Number of Participants Who Experienced a Complete Response (CR) or Partial Response (PR) | 0 Participants |
| Dalotuzumab 10.0 mg/kg / Dalotuzumab 5.0 mg/kg | Number of Participants Who Experienced a Complete Response (CR) or Partial Response (PR) | 0 Participants |
| Dalotuzumab 15.0 mg/kg / Dalotuzumab 5.0 mg/kg | Number of Participants Who Experienced a Complete Response (CR) or Partial Response (PR) | 0 Participants |
| Dalotuzumab 20.0 mg/kg / Dalotuzumab 5.0 mg/kg | Number of Participants Who Experienced a Complete Response (CR) or Partial Response (PR) | 0 Participants |
| Dalotuzumab 15.0 mg/kg / Dalotuzumab 10.0 mg/kg | Number of Participants Who Experienced a Complete Response (CR) or Partial Response (PR) | 0 Participants |
| Dalotuzumab 15.0 mg/kg / Dalotuzumab 15.0 mg/kg | Number of Participants Who Experienced a Complete Response (CR) or Partial Response (PR) | 0 Participants |
Secondary
Number of Participants With a Positive Human-anti-humanized-antibody (HAHA) Titer
The formation of HAHAs may block efficacy by prematurely clearing dalotuzumab and limit the possibility of future dalotuzumab therapy. Blood samples for the measurement of serum levels of HAHAs were obtained prior to treatment with dalotuzumab, and pre-dose Week 3, Week 5, pre-dose every 8 subsequent weeks, and end of treatment (post-study: 4 weeks after last dose of study drug). Positive HAHA status for a participant is defined as testing positive on both the screening and immunodepletion assays at one or more visits.
Time frame: Prior to second and subsequent doses of study drug (Up to 1 year post-first dose)
Population: All participants who received one dose of study therapy.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Dalotuzumab 2.5 mg/kg / Dalotuzumab 2.5 mg/kg | Number of Participants With a Positive Human-anti-humanized-antibody (HAHA) Titer | 0 Participants |
| Dalotuzumab 5.0 mg/kg / Dalotuzumab 5.0 mg/kg | Number of Participants With a Positive Human-anti-humanized-antibody (HAHA) Titer | 0 Participants |
| Dalotuzumab 10.0 mg/kg / Dalotuzumab 5.0 mg/kg | Number of Participants With a Positive Human-anti-humanized-antibody (HAHA) Titer | 0 Participants |
| Dalotuzumab 15.0 mg/kg / Dalotuzumab 5.0 mg/kg | Number of Participants With a Positive Human-anti-humanized-antibody (HAHA) Titer | 2 Participants |
| Dalotuzumab 20.0 mg/kg / Dalotuzumab 5.0 mg/kg | Number of Participants With a Positive Human-anti-humanized-antibody (HAHA) Titer | 1 Participants |
| Dalotuzumab 15.0 mg/kg / Dalotuzumab 10.0 mg/kg | Number of Participants With a Positive Human-anti-humanized-antibody (HAHA) Titer | 1 Participants |
| Dalotuzumab 15.0 mg/kg / Dalotuzumab 15.0 mg/kg | Number of Participants With a Positive Human-anti-humanized-antibody (HAHA) Titer | 0 Participants |
Secondary
Percent Change From Baseline in Serum IGF-1R Protein Level at Week 13
IGF-1R expression was measured in pre- and post-dose biopsy samples using immunohistochemistry (IHC) and enzyme-linked immunosorbent assay (ELISA) assays. Results were expressed as a percent change from baseline in IG1-FR expression for participants pooled across all dose arms in the study and calculated by study week. A post-dose decrease in IGF-1R expression was an indication of target engagement by dalotuzumab. A larger percent change correlated with a greater target engagement.
Time frame: Baseline and Week 13
Population: All participants who took at least one dose of study drug and had available IGF-1R protein data for Baseline and Week 13
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Dalotuzumab 2.5 mg/kg / Dalotuzumab 2.5 mg/kg | Percent Change From Baseline in Serum IGF-1R Protein Level at Week 13 | 138.11 Percent change |
Secondary
Percent Change From Baseline in Serum IGF-1R Protein Level at Week 17
IGF-1R expression was measured in pre- and post-dose biopsy samples using immunohistochemistry (IHC) and enzyme-linked immunosorbent assay (ELISA) assays. Results were expressed as a percent change from baseline in IG1-FR expression for participants pooled across all dose arms in the study and calculated by study week. A post-dose decrease in IGF-1R expression was an indication of target engagement by dalotuzumab. A larger percent change correlated with a greater target engagement.
Time frame: Baseline and Week 17
Population: All participants who took at least one dose of study drug and had available IGF-1R protein data for Baseline and Week 17
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Dalotuzumab 2.5 mg/kg / Dalotuzumab 2.5 mg/kg | Percent Change From Baseline in Serum IGF-1R Protein Level at Week 17 | 140.72 Percent change |
Secondary
Percent Change From Baseline in Serum IGF-1R Protein Level at Week 21
IGF-1R expression was measured in pre- and post-dose biopsy samples using immunohistochemistry (IHC) and enzyme-linked immunosorbent assay (ELISA) assays. Results were expressed as a percent change from baseline in IG1-FR expression for participants pooled across all dose arms in the study and calculated by study week. A post-dose decrease in IGF-1R expression was an indication of target engagement by dalotuzumab. A larger percent change correlated with a greater target engagement.
Time frame: Baseline and Week 21
Population: All participants who took at least one dose of study drug and had available IGF-1R protein data for Baseline and Week 21
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Dalotuzumab 2.5 mg/kg / Dalotuzumab 2.5 mg/kg | Percent Change From Baseline in Serum IGF-1R Protein Level at Week 21 | 150.00 Percent change |
Secondary
Percent Change From Baseline in Serum IGF-1R Protein Level at Week 25
IGF-1R expression was measured in pre- and post-dose biopsy samples using immunohistochemistry (IHC) and enzyme-linked immunosorbent assay (ELISA) assays. Results were expressed as a percent change from baseline in IG1-FR expression for participants pooled across all dose arms in the study and calculated by study week. A post-dose decrease in IGF-1R expression was an indication of target engagement by dalotuzumab. A larger percent change correlated with a greater target engagement.
Time frame: Baseline and Week 25
Population: All participants who took at least one dose of study drug and had available IGF-1R protein data for Baseline and Week 25
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Dalotuzumab 2.5 mg/kg / Dalotuzumab 2.5 mg/kg | Percent Change From Baseline in Serum IGF-1R Protein Level at Week 25 | 157.49 Percent change |
Secondary
Percent Change From Baseline in Serum IGF-1R Protein Level at Week 29
IGF-1R expression was measured in pre- and post-dose biopsy samples using immunohistochemistry (IHC) and enzyme-linked immunosorbent assay (ELISA) assays. Results were expressed as a percent change from baseline in IG1-FR expression for participants pooled across all dose arms in the study and calculated by study week. A post-dose decrease in IGF-1R expression was an indication of target engagement by dalotuzumab. A larger percent change correlated with a greater target engagement.
Time frame: Baseline and Week 29
Population: All participants who took at least one dose of study drug and had available IGF-1R protein data for Baseline and Week 29
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Dalotuzumab 2.5 mg/kg / Dalotuzumab 2.5 mg/kg | Percent Change From Baseline in Serum IGF-1R Protein Level at Week 29 | 174.95 Percent change |
Secondary
Percent Change From Baseline in Serum IGF-1R Protein Level at Week 33
IGF-1R expression was measured in pre- and post-dose biopsy samples using immunohistochemistry (IHC) and enzyme-linked immunosorbent assay (ELISA) assays. Results were expressed as a percent change from baseline in IG1-FR expression for participants pooled across all dose arms in the study and calculated by study week. A post-dose decrease in IGF-1R expression was an indication of target engagement by dalotuzumab. A larger percent change correlated with a greater target engagement.
Time frame: Baseline and Week 33
Population: All participants who took at least one dose of study drug and had available IGF-1R protein data for Baseline and Week 33
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Dalotuzumab 2.5 mg/kg / Dalotuzumab 2.5 mg/kg | Percent Change From Baseline in Serum IGF-1R Protein Level at Week 33 | 158.95 Percent change |
Secondary
Percent Change From Baseline in Serum IGF-1R Protein Level at Week 37
IGF-1R expression was measured in pre- and post-dose biopsy samples using immunohistochemistry (IHC) and enzyme-linked immunosorbent assay (ELISA) assays. Results were expressed as a percent change from baseline in IG1-FR expression for participants pooled across all dose arms in the study and calculated by study week. A post-dose decrease in IGF-1R expression was an indication of target engagement by dalotuzumab. A larger percent change correlated with a greater target engagement.
Time frame: Baseline and Week 37
Population: All participants who took at least one dose of study drug and had available IGF-1R protein data for Baseline and Week 37
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Dalotuzumab 2.5 mg/kg / Dalotuzumab 2.5 mg/kg | Percent Change From Baseline in Serum IGF-1R Protein Level at Week 37 | 186.32 Percent change |
Secondary
Percent Change From Baseline in Serum IGF-1R Protein Level at Week 41
IGF-1R expression was measured in pre- and post-dose biopsy samples using immunohistochemistry (IHC) and enzyme-linked immunosorbent assay (ELISA) assays. Results were expressed as a percent change from baseline in IG1-FR expression for participants pooled across all dose arms in the study and calculated by study week. A post-dose decrease in IGF-1R expression was an indication of target engagement by dalotuzumab. A larger percent change correlated with a greater target engagement.
Time frame: Baseline and Week 41
Population: All participants who took at least one dose of study drug and had available IGF-1R protein data for Baseline and Week 41
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Dalotuzumab 2.5 mg/kg / Dalotuzumab 2.5 mg/kg | Percent Change From Baseline in Serum IGF-1R Protein Level at Week 41 | 173.68 Percent change |
Secondary
Percent Change From Baseline in Serum IGF-1R Protein Level at Week 45
IGF-1R expression was measured in pre- and post-dose biopsy samples using immunohistochemistry (IHC) and enzyme-linked immunosorbent assay (ELISA) assays. Results were expressed as a percent change from baseline in IG1-FR expression for participants pooled across all dose arms in the study and calculated by study week. A post-dose decrease in IGF-1R expression was an indication of target engagement by dalotuzumab. A larger percent change correlated with a greater target engagement.
Time frame: Baseline and Week 45
Population: All participants who took at least one dose of study drug and had available IGF-1R protein data for Baseline and Week 45
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Dalotuzumab 2.5 mg/kg / Dalotuzumab 2.5 mg/kg | Percent Change From Baseline in Serum IGF-1R Protein Level at Week 45 | 140.00 Percent change |
Secondary
Percent Change From Baseline in Serum IGF-1R Protein Level at Week 49
IGF-1R expression was measured in pre- and post-dose biopsy samples using immunohistochemistry (IHC) and enzyme-linked immunosorbent assay (ELISA) assays. Results were expressed as a percent change from baseline in IG1-FR expression for participants pooled across all dose arms in the study and calculated by study week. A post-dose decrease in IGF-1R expression was an indication of target engagement by dalotuzumab. A larger percent change correlated with a greater target engagement.
Time frame: Baseline and Week 49
Population: All participants who took at least one dose of study drug and had available IGF-1R protein data for Baseline and Week 49
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Dalotuzumab 2.5 mg/kg / Dalotuzumab 2.5 mg/kg | Percent Change From Baseline in Serum IGF-1R Protein Level at Week 49 | 137.89 Percent change |
Secondary
Percent Change From Baseline in Serum IGF-1R Protein Level at Week 5
IGF-1R expression was measured in pre- and post-dose biopsy samples using immunohistochemistry (IHC) and enzyme-linked immunosorbent assay (ELISA) assays. Results were expressed as a percent change from baseline in IG1-FR expression for participants pooled across all dose arms in the study and calculated by study week. A post-dose decrease in IGF-1R expression was an indication of target engagement by dalotuzumab. A larger percent change correlated with a greater target engagement.
Time frame: Baseline and Week 5
Population: All participants who took at least one dose of study drug and had available IGF-1R protein data for Baseline and Week 5
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Dalotuzumab 2.5 mg/kg / Dalotuzumab 2.5 mg/kg | Percent Change From Baseline in Serum IGF-1R Protein Level at Week 5 | 150.94 Percent change |
Secondary
Percent Change From Baseline in Serum IGF-1R Protein Level at Week 53
IGF-1R expression was measured in pre- and post-dose biopsy samples using immunohistochemistry (IHC) and enzyme-linked immunosorbent assay (ELISA) assays. Results were expressed as a percent change from baseline in IG1-FR expression for participants pooled across all dose arms in the study and calculated by study week. A post-dose decrease in IGF-1R expression was an indication of target engagement by dalotuzumab. A larger percent change correlated with a greater target engagement.
Time frame: Baseline and Week 53
Population: All participants who took at least one dose of study drug and had available IGF-1R protein data for Baseline and Week 53
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Dalotuzumab 2.5 mg/kg / Dalotuzumab 2.5 mg/kg | Percent Change From Baseline in Serum IGF-1R Protein Level at Week 53 | 198.99 Percent change |
Secondary
Percent Change From Baseline in Serum IGF-1R Protein Level at Week 9
IGF-1R expression was measured in pre- and post-dose biopsy samples using immunohistochemistry (IHC) and enzyme-linked immunosorbent assay (ELISA) assays. Results were expressed as a percent change from baseline in IG1-FR expression for participants pooled across all dose arms in the study and calculated by study week. A post-dose decrease in IGF-1R expression was an indication of target engagement by dalotuzumab. A larger percent change correlated with a greater target engagement.
Time frame: Baseline and Week 9
Population: All participants who took at least one dose of study drug and had available IGF-1R protein data for Baseline and Week 9
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Dalotuzumab 2.5 mg/kg / Dalotuzumab 2.5 mg/kg | Percent Change From Baseline in Serum IGF-1R Protein Level at Week 9 | 150.69 Percent change |
Secondary
Percent Change From Baseline in Serum Insulin-like Growth Factor Receptor Type 1 (IGF-1R) Protein Level at Week 1
IGF-1R expression was measured in pre- and post-dose biopsy samples using immunohistochemistry (IHC) and enzyme-linked immunosorbent assay (ELISA) assays. Results were expressed as a percent change from baseline in IG1-FR expression for participants pooled across all dose arms in the study and calculated by study week. A post-dose decrease in IGF-1R expression was an indication of target engagement by dalotuzumab. A larger percent change correlated with a greater target engagement.
Time frame: Baseline and Week 1
Population: All participants who took at least one dose of study drug and had available IGF-1R protein data for Baseline and Week 1.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Dalotuzumab 2.5 mg/kg / Dalotuzumab 2.5 mg/kg | Percent Change From Baseline in Serum Insulin-like Growth Factor Receptor Type 1 (IGF-1R) Protein Level at Week 1 | 118.56 Percent change |