All Drugs and Chemicals

Protein Kinase Inhibitors

JNJ-26483327

Johnson & Johnson Pharmaceutical Research & Development, L.L. C. Clinical Trial

The purpose of this study is to assess JNJ-26483327 (a drug in development for cancer) for the safety of the drug in patients with advanced solid tumors that have not responded or are no longer responding to available therapies. The absorption, breakdown and elimination of the drug will also be studied.

JNJ-26483327, a multi-targeted reversible kinase inhibitor, is a new drug in development for treatment of cancer. This study will test the safety (the effect on the body) of JNJ-26483327 and the highest dose of JNJ-26483327 that patients with advanced cancer can tolerate will be determined. Antitumor activity of JNJ-26481585 will be evaluated.

JNJ-26483327 will be administered in a continuous regimen (orally twice daily) in 28-day treatment cycles. The dose of JNJ-26483327 will start low and will be increased during the study in groups of 1 to 6 patients. If a patient or a group of patients does not have severe side effects, the next group of patients will get a higher dose. The dose will increase until some patients have severe side effects. The dose will then be decreased to a dose level where severe side effects are observed in less than 1/3 of patients. Once a safe dose level has been determined an additional group of 12-18 patients will be treated. The amount of JNJ-26483327 in the blood will be measured and the effect of the disease will be evaluated in all patients.

Patients will be screened for eligibility within 4 weeks before study treatment is given. The treatment will consist of 28-day treatment cycles in a continuous twice daily dosing regimen.

During Cycle 1, patients are required to stay in the hospital for 2-3 nights and 2 full days. In addition there are 5 daytime visits during Cycles 1 and 2 (combined) that may take up to 6 hours after the morning dose. From Cycle 3 onwards, one hospital visit is required for each cycle of treatment.

Throughout the study, especially during Cycles 1 and 2, patients will undergo frequent blood and urine tests, procedures to assess safety including heart function, and tests to assess the course of the patient's illness. The duration of treatment will depend on adverse effects and whether there is benefit from the treatment. Two weeks after the last dose of the study drug, patients are required to return to the study site for follow-up assessments. Patients will take JNJ-26483327 capsules by mouth twice a day throughout treatment. Patients will be allowed to continue at the same dose level as long as there are no unacceptable side effects, and there is benefit to the patient based on the study doctor's evaluations.

A Safety and Dose-finding Study of JNJ-26483327, a Drug in Development for Cancer, for Patients With Advanced and/or Refractory Solid Malignancies.

An Open-label, Phase I Study to Determine the Safety and Pharmacokinetics of JNJ-26483327, a Multi-targeted Kinase Inhibitor, Administered to Subjects With Advanced Stage and/or Refractory Solid Malignancies

Janssen Pharmaceutica N.V., Belgium

Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

AGS-22M6E

ASG-22CE

Medical Monitor

A study examining the safety of AGS-22M6E or ASG-22CE administered as monotherapy therapy in subjects with malignant solid tumors that express Nectin-4.

AGS-22M6E and ASG-22CE are fully human monoclonal antibody conjugated to a cytotoxic agent monomethyl auristatin E (MMAE) targeting Nectin-4 (Agensys code name AGS-22). The main difference between AGS-22M6E and ASG-22CE is the change in cell line for antibody production. AGS-22M6E and ASG-22CE will be administered at mg/kg doses based on the subjects weight at baseline and doses will not change unless the subjects weight changes by ≥ 10% from their baseline weight or the investigational product Dosage Assessment criteria is met.

Subjects will be prescreened for Nectin-4 expression prior to undergoing screening procedures for the main study. Subjects with tumors positive for Nectin-4 expression may be screened for eligibility into the main study. The dose escalation period is estimated to take between 12 and 18 months depending on whether 3 or 6 subjects are enrolled in a given dose cohort, and the availability of consenting subjects.

Subjects will be treated in the dose escalation phase of the study until the maximum tolerated dose (MTD) and recommended dose for expansion (RDE) has been determined by the data review team (DRT). After the RDE has been determined, subjects will be enrolled into 1 of 3 expansion cohorts. There will be 3 expansion cohorts, each targeting a specific cancer (i.e.,Breast, Bladder and Lung plus other solid tumor cancers). The DRT may recommend stopping the study, adjusting the dose or amending the trial at any time.

The clinical bridging to the ASG-22CE involves treating the subjects with ASG-22CE, irrespective of cancer type, at the next lowest dose level previously determined to be safe for AGS-22M6E. After the initial subjects are treated at the bridging dose with ASG-22CE and have completed the safety assessment, future subjects will only be treated with ASG-22CE throughout the remainder of the study.

A disease assessment will be performed by the investigator at Week 8 (± 14 days). Subjects without evidence of disease progression may continue to receive treatment until disease progression or intolerability.

A Study of the Safety and Pharmacokinetics of AGS-22M6E in Subjects With Malignant Solid Tumors That Express Nectin-4

A Phase 1 Study of the Safety and Pharmacokinetics of Escalating Doses of AGS-22M6E or ASG-22CE Given as Monotherapy Followed by Expansion Cohorts in Subjects With Malignant Solid Tumors That Express Nectin-4

Concentration at the end of infusion (Ceoi) or Cmax, trough concentration (Ctrough), Tmax, partial AUC after first dose (AUC0-21), terminal or apparent terminal half-life (t1/2), systemic clearance (CL), volume of distribution at steady state (Vss)

Incidence of a tumor response is defined as a complete or partial response per Response Criteria for Solid Tumors (RECIST version 1.1)

Agensys, Inc.

Seagen Inc.

Astellas Pharma Inc

Neoplasms

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Rare Diseases

Carcinoma

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Ovarian Diseases

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Endocrine Gland Neoplasms

Adnexal Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Genital Neoplasms, Female

Urogenital Neoplasms

Endocrine System Diseases

Gonadal Disorders

Ovarian Cancer

Ovarian Epithelial Cancer

AGS-8M4

Use Central Contact

This is the first in human study of AGS-8M4 given every 2 weeks to subjects with advanced ovarian cancer. AGS-8M4 will be administered as an IV infusion until the disease worsens.

All Subjects will receive AGS-8M4 treatment. Subjects will be enrolled sequentially into 1 of the 4 planned dose cohorts according to a standard dose escalation study design. A disease assessment will be performed at study week 9 (+/- 3 days). The assessment will be based on clinical signs and symptoms, changes in radiographic images, and changes in CA-125 levels. Subjects without evidence of disease progression may continue to receive AGS-8M4 during the extended treatment period at the dose and schedule of their assigned cohort until disease progression intolerability of AGS-8M4 or consent withdrawal. For subjects that continue dosing, disease assessments will be performed every 8 weeks during the extended treatment period. A safety follow-up visit will occur 4 weeks after the last infusion of AGS-8M4.

A Phase 1 Study of the Safety and Pharmacokinetics of AGS-8M4 in Subjects With Advanced Ovarian Cancer

A Phase 1, Open-label, Multi-center, Dose Escalation Study of the Safety and Pharmacokinetics of AGS-8M4 Given as Monotherapy in Subjects With Advanced Ovarian Cancer

Symptoms and General Pathology

Neoplasm Metastasis

Hyperparathyroidism

Hyperparathyroidism, Secondary

Neoplastic Processes

Parathyroid Diseases

Hormones

Parathyroid Hormone

Participants received a single dose of placebo intravenous (IV) injection after hemodialysis.

Participants received a single dose of etelcalcetide by intravenous (IV) injection after hemodialysis.

Placebo

Single IV injection. The initial dose was 5 mg and dose escalation proceeded with subsequent doses of 10 mg, 20 mg, 40 mg and 60 mg.

Etelcalcetide

Gregory Bell, MD

The purpose of this study is to characterize the safety and tolerability of single rising doses of etelcalcetide in hemodialysis patients with secondary hyperparathyroidism.

Safety, Tolerability and Pharmacokinetics of Etelcalcetide in Hemodialysis Patients With Secondary Hyperparathyroidism

A Double-Blind, Randomized, Placebo-Controlled Study to Assess the Safety and Tolerability of Single Ascending Doses of KAI-4169 in Hemodialysis Subjects With Secondary Hyperparathyroidism

KAI Pharmaceuticals

Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.

Pooled Placebo

Participants received a single dose of 5 mg etelcalcetide IV injection after hemodialysis.

Etelcalcetide 5 mg

Participants received a single dose of 10 mg etelcalcetide IV injection after hemodialysis.

Etelcalcetide 10 mg

Participants received a single dose of 20 mg etelcalcetide IV injection after hemodialysis.

Etelcalcetide 20 mg

Participants received a single dose of 40 mg etelcalcetide IV injection after hemodialysis.

Etelcalcetide 40 mg

Participants received a single dose of 60 mg etelcalcetide IV injection after hemodialysis.

Etelcalcetide 60 mg

Participants in Cohort 1 received single doses of 5 mg etelcalcetide and placebo in a crossover design, 7-14 days apart

Cohort 1: Placebo/Etelcalcetide 5 mg

Participants in Cohort 2 received single doses of 10 mg etelcalcetide and placebo in a crossover design, 7-14 days apart

Cohort 2: Placebo/Etelcalcetide 10 mg

Participants in Cohort 3 received single doses of 20 mg etelcalcetide and placebo in a crossover design, 7-14 days apart

Cohort 3: Placebo/Etelcalcetide 20 mg

Participants in Cohort 4 received a single dose of 40 mg etelcalcetide or placebo in a parallel group design.

Cohort 4: Placebo/Etelcalcetide 40 mg

Participants in Cohort 5 received a single dose of 60 mg etelcalcetide or placebo in a parallel group design.

Cohort 5: Placebo/Etelcalcetide 60 mg

Total

Age, Continuous

Sex: Female, Male

Race

Ethnicity

Study Director

Any adverse events

Serious adverse events

Withdrawal due to adverse events

Deaths due to adverse events

Treatment-related adverse events

All participants who were randomized and received any amount of study medication.

Number of Participants With Adverse Events

30 Minutes

1 Hour

4 Hours

8 Hours

18 Hours

24 Hours

32 Hours

42 Hours

48 Hours

56 Hours

Day 4-Discharge

Day 8

Day 15

Day 29

Participants received a single dose of placebo IV injection after hemodialysis.

Participants who were randomized and received any amount of study medication with available data at each time point. Only participants in Cohorts 4 and 5 had PTH assessed on days 8, 15 and 29.

Percent Change From Baseline in Serum Parathyroid Hormone (PTH)

Participants who were randomized and received any amount of study medication and with available data at each time point. Only participants in Cohorts 4 and 5 had serum corrected calcium assessed on days 8, 15 and 29.

Percent Change From Baseline in Serum Corrected Calcium

Participants who were randomized and received any amount of study medication with available data at each time point

Percent Change From Baseline in Ionized Calcium

Participants who were randomized and received any amount of study medication with available data at each time point.

Percent Change From Baseline in Serum Phosphorus

Percent Change From Baseline in Calcium Phosphorus Product

Participants who were randomized and received any amount of etelcalcetide.

Maximum Observed Plasma Concentration (Cmax) of Etelcalcetide

Participants who were randomized and received any amount of etelcalcetide with available data.

Area Under the Concentration-time Curve From Time 0 to 65 Hours Post-dose for Etelcalcetide

Participants who were randomized and received any amount of etelcalcetide and with available data; The half-life associated with the terminal (log-linear) elimination phase values for the 40 mg dose level were not calculated due to poor log linear regression of the log concentration versus time profile during the terminal phase (r2 values \<0.7).

Observed Area Under the Concentration-time Curve Extrapolated to Infinity (AUCINFobs) for Etelcalcetide

Participants who were randomized and received any amount of etelcalcetide and with available data.

Percent AUC Extrapolated to Infinity (AUCINF) Resulting From Extrapolation From 65 Hours Onward for Etelcalcetide

Overall Study

All subjects will receive a single 30 minute intravenous (IV) infusion of enfortumab vedotin once weekly for the first 3 weeks of every 4 week cycle (i.e., on Days 1, 8 and 15).

Subjects will receive a single 30 minute IV infusion of enfortumab vedotin at a dose level below and escalated up to the preliminary RP2D once weekly for 3 weeks of every 4 weeks (i.e., on Days 1, 8 and 15) until disease progression, intolerability of the investigational product or consent withdrawal. A cycle is 4 weeks.

Subjects will receive a single 30 minute IV infusion of enfortumab vedotin at the preliminary RP2D once weekly for 3 weeks of every 4 weeks (i.e., on Days 1, 8 and 15) until disease progression, intolerability of the investigational product or consent withdrawal. A cycle is 4 weeks.

Subjects will receive a single 30 minute IV infusion of enfortumab vedotin at the preliminary RP2D once weekly for 3 weeks of every 4 weeks (i.e., on Days 1, 8 and 15). A cycle is 4 weeks. Subjects will continue treatment until disease progression, intolerability of enfortumab vedotin, Investigator decision or consent withdrawal.

enfortumab vedotin

Medical Director

The purpose of this study is to evaluate the safety and pharmacokinetics of enfortumab vedotin as well as assess the immunogenicity and antitumor activity in subjects with metastatic urothelial cancer and other malignant solid tumors that express Nectin-4.

All subjects will receive a single 30 minute IV infusion of enfortumab vedotin once weekly for the first 3 weeks of every 4 weeks (i.e., on Days 1, 8, and 15). A cycle is 4 weeks.

This is a 3 part study. Part A will evaluate enfortumab vedotin in subjects with histologically confirmed malignant solid tumors (excluding sarcomas) that are resistant or have recurred. Subjects will continue treatment until disease progression, intolerability of enfortumab vedotin, investigator decision or consent withdrawal. Part A will follow a modified Continual Reassessment Method (mCRM).

Part B, will evaluate enfortumab vedotin in 3 different expansion cohorts: 1) Urothelial cancer subjects with renal insufficiency defined as a Creatinine Clearance ≥ 15 ml/min and \< 30 ml/min, 2) subjects with Metastatic Non Small Cell Lung Cancer (NSCLC) and 3) subjects with Metastatic Ovarian Cancer. With the exception of the renal insufficiency cohort, enrollment into Part B will occur at the recommended phase 2 dose (RP2D) established in Part A. Enrollment into the renal insufficiency cohort will begin at starting dose and escalated using a 3 + 3 dose escalation design. Subjects will continue treatment until disease progression, intolerability of enfortumab vedotin or consent withdrawal.

Part C will evaluate enfortumab vedotin at the RP2D (determined from Part A) in subjects who have been previously treated with immune checkpoint inhibitors (CPI) in the metastatic setting. Subjects will continue treatment until disease progression, intolerability of enfortumab vedotin, investigator decision or consent withdrawal.

All subjects will be followed post-treatment through the 30-day Safety Follow-up Visit.

A Study of Escalating Doses of ASG-22CE Given as Monotherapy in Subjects With Metastatic Urothelial Cancer and Other Malignant Solid Tumors That Express Nectin-4

A Phase 1 Study of the Safety and Pharmacokinetics of Escalating Doses of ASG-22CE Given as Monotherapy in Subjects With Metastatic Urothelial Cancer and Other Malignant Solid Tumors That Express Nectin-4

Access to anonymized individual participant level data collected during the study, in addition to study-related supporting documentation, is planned for studies conducted with approved product indications and formulations, as well as compounds terminated during development. Studies conducted with product indications or formulations that remain active in development are assessed after study completion to determine if Individual Participant Data can be shared. Conditions and exceptions are described under the Sponsor Specific Details for Astellas on www.clinicalstudydatarequest.com.

Incidence of tumor response defined as either a complete response (CR) or partial response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST) criteria (version 1.1) that is confirmed ≥ 28 days later

Defined as the percentage of subjects who experience a best response of either CR or PR in that cohort. CR and PR must be confirmed ≥ 28 days later.

Defined as the percentage of subjects who experience a best response of CR, PR or stable disease (SD)

Time from the date of first infusion to the earliest date of documented disease progression per radiological evidence or death from any cause

Time from the date of first infusion until the date of death from any cause.

Time from the date of the first response complete response (CRC) or partial response (PR) to the earliest date of disease progression or death from any cause. DOR is only defined for subjects who have best overall response of CR or PR

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Safety and Dose-finding Study of JNJ-26483327, a Drug in Development for Cancer, for Patients With Advanced and/or Refractory Solid Malignancies.	NCT00676299	Protein Kinase ... Antineoplastic ... Clinical Trial,... Maximum Tolerat... Pharmacokinetic... Advanced Malign... Solid Malignanc...	JNJ-26483327	18 Years -	Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
A Study of the Safety and Pharmacokinetics of AGS-22M6E in Subjects With Malignant Solid Tumors That Express Nectin-4	NCT01409135	Tumors Medical Oncolog... Neoplasms	AGS-22M6E ASG-22CE	18 Years -	Astellas Pharma Inc
A Phase 1 Study of the Safety and Pharmacokinetics of AGS-8M4 in Subjects With Advanced Ovarian Cancer	NCT00816764	Carcinoma Ovarian Cancer Ovarian Disease... Ovarian Neoplas...	AGS-8M4	18 Years -	Astellas Pharma Inc
Safety, Tolerability and Pharmacokinetics of Etelcalcetide in Hemodialysis Patients With Secondary Hyperparathyroidism	NCT01134562	Hyperparathyroi...	Placebo Etelcalcetide	18 Years -	KAI Pharmaceuticals
A Study of Escalating Doses of ASG-22CE Given as Monotherapy in Subjects With Metastatic Urothelial Cancer and Other Malignant Solid Tumors That Express Nectin-4	NCT02091999	Metastatic Urot...	enfortumab vedo...	18 Years -	Astellas Pharma Inc
Safety, Tolerability and Pharmacokinetics of Etelcalcetide in Hemodialysis Patients With Secondary Hyperparathyroidism	NCT01134562	Hyperparathyroi...	Placebo Etelcalcetide	18 Years -	KAI Pharmaceuticals
A Study of Escalating Doses of ASG-22CE Given as Monotherapy in Subjects With Metastatic Urothelial Cancer and Other Malignant Solid Tumors That Express Nectin-4	NCT02091999	Metastatic Urot...	enfortumab vedo...	18 Years -	Astellas Pharma Inc

Spots Global Cancer Trial Database for clinical trial, phase 1