Neoplasms

Digestive System Diseases

Gland and Hormone Related Diseases

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Symptoms and General Pathology

Rare Diseases

Pancreatic Neoplasms

Death

Gastrointestinal Neoplasms

Digestive System Neoplasms

Endocrine Gland Neoplasms

Gastrointestinal Diseases

Pancreatic Diseases

Endocrine System Diseases

Pancreatic Cancer

All Drugs and Chemicals

Antineoplastic Agents

Antibodies

Antibodies, Monoclonal

Gemcitabine

Immunoglobulins

Immunologic Factors

Antimetabolites

CS-1008: 8mg/kg loading dose followed by 3mg/kg weekly.

CS-1008 (humanized anti-DR5 antibody)

gemcitabine

Global Clinical Leader

Phase 2 study to determine the efficacy and safety of CS-1008 when given with gemcitabine to subjects with previously untreated and unresectable (unable to be surgically removed) or metastatic (spread to other areas beyond the pancreas) pancreatic cancer.

Primary Objective:

- To evaluate the efficacy of CS-1008 administered in combination with gemcitabine to chemotherapy naive subjects with unresectable or metastatic pancreatic cancer, based on the progression-free survival at 16 weeks.

Secondary Objectives:

* To evaluate the efficacy of CS-1008 administered in combination with gemcitabine on overall progression-free survival rate, objective response rate, duration of response, and overall survival.
* To determine the pharmacokinetics of BIP CS-1008 and DSC CS-1008.
* To study potential biomarkers of CS-1008 activity
* To assess possible human anti-human antibody formation after exposure to CS-1008
* To evaluate the safety profile of CS-1008 when administered in combination with gemcitabine to chemotherapy naive subjects with unresectable or metastatic pancreatic cancer.

Open-label Study of CS-1008 for Subjects With Untreated and Unresectable Pancreatic Cancer

Phase 2 Multicenter, Open-Label Study of CS-1008, A Humanized Monoclonal Antibody Targeting Death Receptor 5 (DR5), In Combination With Gemcitabine in Chemotherapy Naive Subjects With Unresectable or Metastatic Pancreatic Cancer

Progression-free survival rate (PFS) was defined as the time from the date of the first administration of the study drug (Day 1) to the date of the first objective documentation of disease progression or death resulting from any cause, whichever came first at 16 weeks post-treatment with CS-1008.

PFS (Progression-free survival) was defined as the time from the date of the first administration of study drug (Day 1) to the date of the first objective documentation of disease progression or death resulting from any cause, whichever came first.

OS (Overall Survival) was defined as the time from the date of the first administration of study drug (Day 1) to the date of death. If there was no death reported for a subject before the cut-off date for overall survival analysis, overall survival was censored at the last contact date at which the subject was known to be alive.

The best overall response the best response (in the order of confirmed complete response \[CR\], confirmed partial response \[PR\], unconfirmed CR, unconfirmed PR, stable disease \[SD\], and progressive disease\[PD\]) among all overall responses recorded from the start of treatment until the subject withdrew from the study. If there was no tumor assessment after the first infusion of study drug and no clinical disease progression recorded, the best overall response was classified as Unknown. CR was defined as the disappearance of all target lesions, PR was defined as at least a 30% decrease in the sum of diameters of target lesions, PD was defined as at least a 20% increase in the sum of diameters of target lesions, and SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease PD according to RECIST guideline (version 1.1).

A treatment-emergent adverse event (TEAE) was defined as an adverse event (AE) that: emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment or worsens in severity during treatment relative to the pre-treatment state when the AE was continuous. The AEs with an onset date on Day 1 (the date on which the first dose of study medication was administered) were counted as a TEAE. An AE that occurred more than 30 days after the last dose of study medication was not included as a TEAE unless it was considered drug-related. A TEAE was considered related to CS-1008 or gemcitabine if the investigator considered the event as possibly, probably, or definitely related to treatment, or if the investigator's assessment of the relationship was unknown.

Daiichi Sankyo

A treatment-emergent AE (TEAE) was defined as an AE that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity during treatment after initiating the study drug until 30 days after last dose of the study drug, unless it was considered drug related.

Chemotherapy-naïve participants with unresectable or metastatic pancreatic cancer who were administered CS-1008 once weekly without rest, and Gemcitabine once weekly for 3 weeks followed by 1 week of rest. CS-1008 was administered first. Gemcitabine was then administered immediately after completion of the CS-1008 infusion.

CS-1008 + Gemcitabine

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

The safety analysis set included all subjects who received any amount of study drug infusion (ie, CS-1008 or gemcitabine). This analysis set was used to summarize safety variables.

Contact for Clinical Trial Information

The progression-free survival rate was assessed in the Per-Protocol Analysis Set.

Progression-Free Survival Rate at 16 Weeks Following Treatment With CS-1008 in Combination With Gemcitabine in Chemotherapy-Naïve Participants With Unresectable or Metastatic Pancreatic Cancer

PFS Rate at 3 Months (%)

PFS Rate at 6 Months (%)

PFS Rate at 9 Months (%)

PFS Rate at 1 Year (%)

Progression-free survival was assessed in the Per-Protocol Analysis Set.

Kaplan-Meier (Non-Parametric) Analysis of Progression-Free Survival Following Treatment With CS-1008 in Combination With Gemcitabine in Chemotherapy-Naïve Participants With Unresectable or Metastatic Pancreatic Cancer

OS Rate at 6 Months (%)

OS Rate at 9 Months (%)

OS Rate at 1 Year (%)

OS Rate at 15 Months (%)

Overall survival was assessed in the Per-Protocol Analysis Set.

Overall Survival Following Treatment With CS-1008 in Combination With Gemcitabine in Chemotherapy-Naïve Participants With Unresectable or Metastatic Pancreatic Cancer

Confirmed CR

Confirmed PR

Objective Response (confirmed CR or PR)

Unconfirmed CR

Unconfirmed PR

Stable Disease (SD)

Progressive Disease (PD)

Unknown

The best overall tumor response was assessed in the Per-Protocol Analysis Set.

Best Overall Tumor Response Following Treatment With CS-1008 in Combination With Gemcitabine in Chemotherapy-Naïve Participants With Unresectable or Metastatic Pancreatic Cancer

Any TEAE

Anemia

Neutropenia

Thrombocytopenia

Abdominal Pain

Constipation

Diarrhea

Nausea

Vomiting

Asthenia

Fatigue

Oedma peripheral

Pyrexia

Haemoglobin decreased

Neutrophil count decreased

White blood cell count decreased

Anorexia

Dysgeusia

Headache

Rash

Hypertension

Treatment-Emergent Adverse Events were assessed in the safety analysis set.

Number of Participants With Treatment-Emergent Adverse Events Considered by the Investigator at Least Possibly Related to CS-1008 Experienced by ≥5% of Participants by System Organ Class and Preferred Term

Leukopenia

Lymphopena

Abdominal distension

Abdominal pain

Chills

Oedema peripheral

Platelet count decreased

Dehydration

Alopecia

Night Sweats

Treatment-emergent adverse event was assessed in the safety analysis set.

Number of Participants With Treatment-Emergent Adverse Events Considered by the Investigator at Least Possibly Related to Gemcitabine Experienced by ≥5% of Participants by System Organ Class and Preferred Term

Overall Study

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Open-label Study of CS-1008 for Subjects With Untreated and Unresectable Pancreatic Cancer	NCT00521404	Pancreatic Canc...	CS-1008 (humani... gemcitabine	18 Years -	Daiichi Sankyo
Open-label Study of CS-1008 for Subjects With Untreated and Unresectable Pancreatic Cancer	NCT00521404	Pancreatic Canc...	CS-1008 (humani... gemcitabine	18 Years -	Daiichi Sankyo

Spots Global Cancer Trial Database for unresectable or metastatic pancreatic cancer