Neoplasms

Heart and Blood Diseases

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Multiple Myeloma

Neoplasms, Plasma Cell

Neoplasms by Histologic Type

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hematologic Diseases

Hemorrhagic Disorders

Lymphoproliferative Disorders

Immunoproliferative Disorders

Participants received dalotuzumab 1.25 mg/kg (10 mg/mL) intravenous (IV) infusion 1 time every 1 week (Q1W).

Participants received dalotuzumab 2.5 mg/kg (10 mg/mL) IV infusion Q1W.

Participants received dalotuzumab 5 mg/kg (10 mg/mL) IV infusion Q1W.

Participants received dalotuzumab 10 mg/kg (10 mg/mL) IV infusion Q1W.

Participants received dalotuzumab 10 mg/kg (20 mg/mL) IV infusion Q1W.

Participants received dalotuzumab 15 mg/kg (10 mg/mL) IV infusion Q1W.

Participants received dalotuzumab 15 mg/kg (20 mg/ mL) IV infusion Q1W.

Participants received dalotuzumab 20 mg/kg (10 mg/mL) IV infusion Q1W.

Participants received dalotuzumab 20.0 mg/kg (20 mg/mL) IV infusion Q1W.

Participants received dalotuzumab 20 mg/kg (20 mg/mL) IV infusion 1 time every 2 weeks (Q2W).

Participants received dalotuzumab 30 mg/kg (20 mg/mL) IV infusion1 time every 3 weeks (Q3W).

Dalotuzumab

Medical Director

This study will look for the highest tolerated dose of dalotuzumab (MK-0646) given as weekly, every other week. or a every three week infusion.

The hypothesis of this study is that administration of dalotuzumab as a one- to two-hour weekly, every other week, or every three week infusion in participants with advanced cancer will be generally safe and tolerated at a dose which achieves a trough concentration ≥3 μg/mL.

Trial Duration of Treatment: Participants can be treated for up to two years if their disease has not progressed and they are not having unmanageable side effects.

Dose Escalation Trial of Dalotuzumab (MK-0646) in Advanced Solid Tumors and Multiple Myeloma (MK-0646-001)

An Open-Label, Dose Escalation Phase I Trial of MK-0646 Given as a Once Weekly, Every Other Week, or Every Three Week Infusion in Patients With Advanced Solid Tumors and Multiple Myeloma

https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf

Toxicity was graded and recorded according to National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events version 3.0 (CTCAE 3.0). A DLT was defined as any Grade 3 or 4 toxicity. A Grade 3 toxicity was defined as severe or medically significant but not immediately life-threatening OR hospitalization or prolongation of hospitalization indicated OR disabling OR limiting self care activities of daily living. A Grade 4 toxicity was defined as: life-threatening consequences OR urgent intervention indicated. Participants were monitored for the occurrence of DLTs during the first 3 weeks of dosing with dalotuzumab.

Terminal half-life is defined as the time it takes for the blood plasma concentration of a substance to halve (plasma half-life). Blood samples for measurement of serum levels of dalotuzumab were obtained at: pre-dose; pre-end infusion; 0.5, 5, 10, 24, 30 (Q1W only), 48, 96, 168 (Q2W/Q3W only), 336 (Q3W only) hours post infusion. For infusions \>1 hour in duration, an additional sample was obtained at the mid-point of the infusion. Data presented are for the harmonic mean t1/2 for dalotuzumab.

AUC0-∞ represents the total drug exposure over time. Blood samples for measurement of serum levels of dalotuzumab were obtained at: Predose; pre-end infusion; 0.5, 5, 10, 24, 30 (Q1W only), 48, 96, 168 (Q2W/Q3W only), 336 (Q3W only) hours post-infusion. For infusions \>1 hour in duration, an additional sample was obtained at the mid-point of the infusion.

Clearance is defined as the volume of serum from which study drug was completely removed per unit of time. Blood samples for measurement of serum levels of dalotuzumab were obtained at: pre-dose; pre-end infusion; 0.5, 5, 10, 24, 30 (Q1W only), 48, 96, 168 (Q2W/Q3W only), 336 (Q3W only) hours post infusion. For infusions \>1 hour in duration, an additional sample was obtained at the mid-point of the infusion.

The lowest (trough) concentration of dalotuzumab prior to the next dose of dalotuzumab was measured.

IGF-1R expression was measured in pre- and post-dose skin biopsy samples using an immunohistochemistry (IHC) assay as a function of time and dose. Results were expressed as an IGF-1R membrane H-score which could range from 0 to 300; with a score of 0 representing the absence of IGF-1R expression and an H-score of 300 representing maximum IGF-1R expression. Changes in IGF-1R expression levels from Baseline are summarized for all participants for whom these paired data were available. A post-dose decrease in IGF-1R membrane H-score was an indication of target engagement by dalotuzumab. A larger decrease in H-score correlated with a greater target engagement.

IGF-1R expression was measured in pre- and post-dose tumor biopsy samples using an IHC assay as a function of time and dose. Results were expressed as an IGF-1R membrane H-score which could range from 0 to 300; with a score of 0 representing the absence of IGF-1R expression and an H-score of 300 representing maximum IGF-1R expression. Changes in IGF-1R expression levels from Baseline are summarized for all participants for whom these paired data were available. A post-dose decrease in IGF-1R membrane H-score was an indication of target engagement by dalotuzumab. A larger decrease in H-score correlated with a greater target engagement.

It is thought that 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 2 (Q1W), pre-dose Week 3 (Q2W), pre-dose Week 4 (QW3), pre-dose Week 5 (Q1W/Q2W), pre-dose Week 7 (Q2W/Q3W), pre-dose Week 9 (Q2W), pre-dose Week 10 (QW3) and pre-dose every 4 subsequent weeks and end of treatment (post-study: 4 weeks after last dose of study drug).

Tumor responses were measured by using Response Evaluation Criteria in Solid Tumors (RECIST) criteria in participants with solid tumors and using European Group for Blood and Marrow Transplantation (EBMT) criteria in participants with multiple myeloma. RECIST criteria for CR: Disappearance of all target lesions. RECIST criteria for PR: ≥30% decrease in the sum of diameters of target lesions. EBMT criteria for CR: Disappearance of the original mAb protein from the blood and urine AND \<5% plasma cells in the bone marrow AND no increase in the size or number of lytic bone lesions AND disappearance of soft tissue plasmacytomas AND normal serum calcium levels. EMBT criteria for PR: ≥50% reduction in the serum mAb protein level AND if a urine M-component is present, a reduction in 24-hour urinary light chain excretion by either ≥90% or to \<200 mg AND ≥50% reduction in the size of soft tissue plasmacytomas AND no increase in size or number of lytic bone lesions.

Merck Sharp & Dohme LLC

The population consisted of all participants who received at least one dose of study drug.

Participants received dalotuzumab 1.25 mg/kg (10 mg/mL) IV infusion Q1W.

Dalotuzumab 1.25 mg/kg Q1W (10 mg/mL)

Dalotuzumab 2.5 mg/kg Q1W (10 mg/mL)

Dalotuzumab 5 mg/kg Q1W (10 mg/mL)

Dalotuzumab 10 mg/kg Q1W (10 mg/mL)

Dalotuzumab 10 mg/kg Q1W (20 mg/mL)

Dalotuzumab 15 mg/kg Q1W (10 mg/mL)

Participants received dalotuzumab 15 mg/kg (20 mg/mL) IV infusion Q1W.

Dalotuzumab 15 mg/kg Q1W (20 mg/mL)

Dalotuzumab 20 mg/kg Q1W (10 mg/mL)

Participants received dalotuzumab 20 mg/kg (20 mg/mL) IV infusion Q1W.

Dalotuzumab 20 mg/kg Q1W (20 mg/mL)

Participants received dalotuzumab 20 mg/kg (20 mg/mL) IV infusion Q2W.

Dalotuzumab 20 mg/kg Q2W (20 mg/mL)

Participants received dalotuzumab 30 mg/kg (20 mg/mL) IV infusion Q3W.

Dalotuzumab 30 mg/kg Q3W (20 mg/mL)

Total

Age, Continuous

Sex: Female, Male

Senior Vice President, Global Clinical Development

Percentage of Participants Who Experienced One or More Dose-limiting Toxicities (DLTs)

The population consisted of all evaluable participants who received \>90% of intended drug volume and had t1/2 pharmacokinetic measurements at Baseline and at least once during treatment.

Mean Terminal Half-life (t1/2) of Dalotuzumab

The population consisted of all evaluable participants who received \>90% of intended drug volume and had AUC0-last pharmacokinetic measurements at Baseline and at least once during treatment.

Area Under the Time-concentration Curve From 0 to Infinity Hours (AUC0-∞) of Dalotuzumab

The population consisted of all evaluable participants who received \>90% of intended drug volume and had mean serum clearance pharmacokinetic measurements at Baseline and at least once during treatment.

Mean Serum Clearance of Dalotuzumab

The population consisted of all evaluable participants who received \>90% of intended drug volume and had mean trough serum concentration pharmacokinetic measurements at Baseline and at least once during treatment.

Mean Trough Serum Concentration (Ctrough) of Dalotuzumab

Baseline

Change from Baseline

Participants received dalotuzumab 10 mg/kg IV infusion Q1W.

Participants received dalotuzumab 15 mg/kg IV infusion Q1W.

Participants received dalotuzumab 20 mg/kg IV infusion Q1W or Q2W.

The population consisted of all evaluable participants who received \>90% of intended drug volume and had skin IGF-1R pharmacodynamics measurements at Baseline and at least once during treatment. No data were available for the Dalotuzumab 30 mg/kg Q3W treatment group.

Change From Baseline in Insulin-like Growth Factor Receptor Type 1 (IGF-1R) Protein Expression Level H-score in Skin Samples

The population consisted of all evaluable participants who received \>90% of intended drug volume and had IGF-1R tumor pharmacodynamics measurements at Baseline and at least once during treatment. No data were available for the Dalotuzumab 2.5 mg/kg Q1W and Dalotuzumab 30 mg/kg Q3W treatment groups.

Change From Baseline in IGF-1R Protein Expression Level H-score in Tumor Samples

The population consisted of all participants who received \>90% of intended drug volume and had measurements at Baseline and at least once during treatment.

Percentage of Participants Who Developed a Serum Human-anti-humanized-antibody (HAHA) Response to Dalotuzumab

The population consisted of all evaluable participants who received \>90% of intended drug volume and had efficacy measurements at Baseline and at least once during treatment.

Percentage of Participants Who Experienced a Complete Response (CR) or Partial Response (PR)

Participants received dalotuzumab 30 mg/kg (20 mg/mL) IV infusion 1 time every 3 weeks (Q3W).

Spots Global Cancer Trial Database for Dose Escalation Trial of Dalotuzumab (MK-0646) in Advanced Solid Tumors and Multiple Myeloma (MK-0646-001)

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

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Contact Details

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