Phase 3
Completed N=780
A Study of Pertuzumab in Combination With Trastuzumab and Chemotherapy in Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Metastatic Gastroesophageal Junction or Gastric Cancer
Source: ClinicalTrials.gov NCT01774786 ↗Enrolled (actual)
780
Serious AEs
43.2%
Results posted
Feb 2018
Primary outcomePrimary: Overall Survival — 17.5; 14.2; 18.1; 14.2 Months — p=0.0565
◆ Published Evidence
Highly cited
480citations · ~60 / year
Pertuzumab plus trastuzumab and chemotherapy for HER2-positive metastatic gastric or gastro-oesophageal junction cancer (JACOB): final analysis of a double-blind, randomised, placebo-controlled phase 3 study.
Summary
This double-blind, placebo-controlled, randomized, multicenter, international, parallel arm study will evaluate the efficacy and safety of pertuzumab in combination with trastuzumab, fluoropyrimidine and cisplatin as first-line treatment in participants with HER2-positive metastatic gastroesophageal junction (GEJ) or gastric cancer (GC). Participants will be randomized to receive pertuzumab 840 milligrams (mg) or placebo intravenously every 3 weeks (q3w) in combination with trastuzumab (initial dose of 8 milligrams per kilogram [mg/kg] intravenously [IV] followed by 6 mg/kg IV q3w) and cisplatin and fluoropyrimidine (capecitabine or 5-fluorouracil) for the first 6 treatment cycles. Participants will continue to receive pertuzumab or placebo and trastuzumab until disease progression occurrence of unacceptable toxicity or withdrawal from the study for another reason.
Linked Publications (4)
-
Pertuzumab plus trastuzumab and chemotherapy for HER2-positive metastatic gastric or gastro-oesophageal junction cancer (JACOB): final analysis of a double-blind, randomised, placebo-controlled phase 3 study.
-
Pertuzumab, trastuzumab, and chemotherapy in HER2-positive gastric/gastroesophageal junction cancer: end-of-study analysis of the JACOB phase III randomized clinical trial.
-
Pertuzumab in combination with trastuzumab and chemotherapy for Chinese patients with HER2-positive metastatic gastric or gastroesophageal junction cancer: a subpopulation analysis of the JACOB trial.
-
Pharmacokinetic and exposure-response analysis of pertuzumab in patients with HER2-positive metastatic gastric or gastroesophageal junction cancer.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Overall Survival |
17.5; 14.2; 18.1; 14.2 | 0.0565 |
| SECONDARY Progression-Free Survival, as Determined by the Investigator According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) Criteria |
8.5; 7.0; 8.5; 7.2 | — |
| SECONDARY Primary Analysis of the Percentage of Participants With Overall Objective Response, as Determined by the Investigator According to RECIST v1.1 Criteria |
56.7; 48.3; 5.1; 0.9; 51.6; 47.4 | — |
| SECONDARY Final Analysis of the Percentage of Participants With Overall Objective Response, as Determined by the Investigator According to RECIST v1.1 Criteria |
57.0; 48.6; 5.7; 2.0; 51.3; 46.6 | — |
| SECONDARY Duration of Objective Response, as Determined by Investigator According to RECIST v1.1 Criteria |
10.2; 8.4; 10.2; 8.4 | — |
| SECONDARY Percentage of Participants With Clinical Benefit, as Determined by the Investigator According to RECIST v1.1 Criteria |
84.6; 81.3 | — |
| SECONDARY Overview of Safety: Number of Participants With at Least One Adverse Event, Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 4.03 |
381; 385; 27; 31; 178; 156 | — |
| SECONDARY Number of Participants With Symptomatic or Asymptomatic Left Ventricular Systolic Dysfunction (LVSD) |
3; 1; 20; 18 | — |
| SECONDARY Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score |
26.68; 27.59; 6.57; 0.97; 3.63; 3.81 | — |
| SECONDARY Change From Baseline in EORTC QLQ-Gastric Cancer Module (EORTC QLQ-STO22) Score |
40.10; 40.48; -2.58; -4.11; -4.14; -3.87 | — |
| SECONDARY Maximum Serum Concentration (Cmax) of Pertuzumab |
258; 288; 341; 371 | — |
| SECONDARY Cmax of Trastuzumab |
142; 139; 120; 120; 127; 129 | — |
| SECONDARY Minimum Serum Concentration (Cmin) of Pertuzumab |
NA; 42.4; 74.0; 90.4; 114; 142 | — |
| SECONDARY Cmin of Trastuzumab |
NA; NA; 15.4; 17.2; 19.9; 20.7 | — |
Eligibility Criteria
Inclusion Criteria
- Histologically confirmed metastatic adenocarcinoma of the stomach or GEJ
- Measurable or evaluable non-measurable disease as assessed by the investigator according to RECIST v1.1 criteria
- Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
- Life expectancy greater than equal to (>/=) 3 months
Exclusion Criteria
- Previous cytotoxic chemotherapy for advanced (metastatic) disease
- Evidence of disease progression documented within 6 months after completion of prior neoadjuvant or adjuvant cytotoxic chemotherapy, or both, or radiotherapy for GEJ adenocarcinoma
- Previous treatment with any HER2-directed therapy, at any time, for any duration
- Previous exposure to any investigational treatment within 30 days before the first dose of study treatment
- Radiotherapy within 30 days before the first dose of study treatment (within 2 weeks if given as palliation to bone metastases, if recovered from all toxicities)
- History or evidence of brain metastases
- Clinically significant active gastrointestinal (GI) bleeding (Grade >/=2 according to National Cancer Institute [NIC]-Common Terminology Criteria for Adverse Events Version 4.0 [CTCAEv.4.0])
- Residual toxicity resulting from previous therapy (for example, hematologic, cardiovascular, or neurologic toxicity that is Grade >/=2). Alopecia is permitted
- Other malignancy (in addition to gastric cancer [GC]) within 5 years before enrollment, except for carcinoma in situ of the cervix or squamous or basal cell carcinoma of the skin that has been previously treated with curative intent
- Inadequate hematologic, renal or liver function
- Pregnant or lactating women
- History of congestive heart failure of any New York Heart Association (NYHA) criteria
- Angina pectoris requiring treatment
- Myocardial infarction within the past 6 months before the first dose of study drug
- Clinically significant valvular heart disease or uncontrollable high-risk cardiac arrhythmia
- History or evidence of poorly controlled hypertension
- Baseline left ventricular ejection fraction (LVEF) value less than (<) 55 percent (%)
- Any significant uncontrolled intercurrent systemic illness
- Positive for hepatitis B, hepatitis C or human immunodeficiency virus (HIV) infection
Data sourced from ClinicalTrials.gov (NCT01774786) and the linked publication. Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.