Study of Patritumab in Combination With Erlotinib in Subjects With Locally Advanced or Metastatic Non-Small-Cell Lung Cancer (NSCLC). (HER3-Lung)

Lung Cancer Clinical Trial

— HER3-Lung  

Official title:

Phase 3, Randomized, Placebo-Controlled, Double-Blind, Multi-Center, Two-Part Study of Patritumab (U3-1287) In Combination With Erlotinib in EGFR Wild-type Subjects With Locally Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC) Who Have Progressed on at Least One Prior Systemic Therapy

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02134015
• Other study ID #: U31287-A-U301
• Secondary ID: 2013-004371-12
• Status: Terminated
• Phase: Phase 3
• First received: April 8, 2014
• Last updated: December 22, 2017
• Start date: March 2014
• Est. completion date: November 11, 2016

Study information

• Verified date: December 2017
• Source: Daiichi Sankyo, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

1. Part A: Subjects will receive Patritumab or placebo with erlotinib. Progression-free survival will be the primary outcome. Subjects will need to have Epidermal Growth Factor Receptor (EGFR) wild-type, locally advance or metastatic NSCLC and have their cancer progressed after at least one prior systemic anti-cancer therapy, available recent or archival tumor specimen and may not have had previous EGFR-targeted regimen, anti-HER2 (Human Epidermal Growth Factor Receptor 2), anti-HER3, or anti-HER4 therapy. Subjects may have high heregulin or low heregulin.

2. Part B: Subjects will receive Patritumab or placebo with erlotinib. Overall survival will be the primary outcome. Subjects will need to have EGFR wild-type, locally advance or metastatic NSCLC and have their cancer progressed after at least one prior systemic anti-cancer therapy, available recent or archival tumor specimen and may not have had previous EGFR-targeted regimen, anti-HER2, anti-HER3, or anti-HER4 therapy. Only subjects with high heregulin will be enrolled.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 145
• Est. completion date: November 11, 2016
• Est. primary completion date: November 11, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years and older

Eligibility

Inclusion Criteria:

1. Must be greater or equal to 20 years of age

2. Must have cytologically or histologically confirmed NSCLC with either:

• Metastatic disease (Stage IV) OR

• Stage IIIB disease not amenable to surgery or curative intent.

Note: It is permissible to use either AJCC Version 6.0 or the AJCC Version 7.0 staging system. For sites that use AJCC Version 7.0, T4M0 patients with other ipsilateral nodules and N0-N2 are still eligible.

3. If tumor histology is adenocarcinoma, must have wild-type EGFR genotype as assessed by a validated assay that includes exon 19 deletion and exon 21 (L858R) substitution.

4. Must have received one or two prior lines of systemic chemotherapy for advanced or metastatic disease, one of which must be a platinum-doublet therapy.

5. Must have disease progression or recurrence documented by radiographic assessment following treatment after last chemotherapy or chemoradiation regimen (completed within the previous 12 months).

6. Must have available recent (before treatment start) or archival tumor specimen.

7. Must have measurable disease for Part A, measurable disease or non-measurable disease for Part B

8. Must have Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

9. Must have adequate hematological function

10. Must have adequate renal function

11. Must have adequate hepatic function

12. Agreement to use effective contraception while on treatment and for at least 6 months after end of treatment

13. Must have provided informed consent for study participation.

Exclusion Criteria:

1. Lung adenocarcinoma with an Anaplastic Lymphoma Kinase (ALK) gene rearrangement

2. Left ventricular ejection fraction (LVEF) less than 45%

3. Prior EGFR-targeted regimen, anti-HER2, anti-HER3, or anti-HER4 therapy

4. History of other malignancies, except adequately treated non-melanoma skin cancer, curatively treated in-situ disease, or other solid tumors curatively treated with no evidence of disease for greater or equal to 5 years

5. History of corneal disease

6. History of interstitial lung disease (ILD)

7. Clinically active brain metastases

8. Uncontrolled hypertension

9. Clinically significant ECG changes

10. Clinically significant (in the opinion of the Investigator) ascites or pleural effusion requiring chronic medical intervention

11. Myocardial infarction within 1 year before enrollment, symptomatic congestive heart failure, unstable angina, or unstable cardiac arrhythmia requiring medication

12. Treatment with anticancer therapy, antibody-based therapy, retinoid therapy, or hormonal therapy within 4 weeks before study drug treatment

13. Therapeutic radiation therapy or major surgery within 4 weeks before study drug treatment; or palliative radiation within 2 weeks before study drug treatment

14. Participation in clinical drug trials within 4 weeks

15. Uncontrolled infection requiring IV antibiotics, antivirals, or antifungals, known human immunodeficiency virus (HIV) infection, or active hepatitis B or C infection.

16. History of hypersensitivity to any of the study drugs or to any excipients.

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Cancer
• Lung Neoplasms
• Non-small Cell Lung Cancer

Intervention

Drug:
• Patritumab
Infusion of Patritumab (loading dose of 18 mg/kg, followed by 9 mg/kg every 3 weeks)
• Erlotinib
Oral erlotinib 150 mg/day
• Placebo
Placebo infusion every 3 weeks

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Daiichi Sankyo, Inc.	Parexel

Countries where clinical trial is conducted

United States,  Belgium,  Canada,  Czechia,  Germany,  Hungary,  Italy,  Poland,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Part A: Progression Free Survival (PFS) in Heregulin-high Participants	PFS is defined as the time from the date of randomization to the earlier of the dates of first objective documentation of radiographic disease progression (as per RECIST Version 1.1 per investigator assessment) or death resulting from any cause.; Kaplan-Meier Estimate. Confidence interval (CI) for median was computed using the Brookmeyer-Crowley method. 80% confidence interval is included in the data table.	by trial termination (at 20 months)
Primary	Part A: Progression Free Survival (PFS) in Heregulin-low Participants	PFS is defined as the time from the date of randomization to the earlier of the dates of first objective documentation of radiographic disease progression (as per RECIST Version 1.1 per investigator assessment) or death resulting from any cause.; Kaplan-Meier Estimate. Confidence interval (CI) for median was computed using the Brookmeyer-Crowley method. 80% confidence interval is included in the data table.	by trial termination (at 20 months)
Primary	Part B: Overall Survival	Percentage of participants still alive at the end of Part B	4 years
Secondary	Part A: Overall Survival in HRG High Participants	Key secondary efficacy endpoint: Percentage of participants who survived for the length of the trial	by trial termination (at 20 months)
Secondary	Part A: Key Secondary Efficacy Endpoint: Overall Survival in HRG Low Participants	Key secondary efficacy endpoint: Percentage of participants who survived for the length of the trial	by trial termination (at 20 months)
Secondary	Part B: Key Secondary Efficacy Endpoint: PFS, TTD	PFS is defined as the time from the date of randomization to the earlier of the dates of first objective documentation of radiographic disease progression (TTD, as per RECIST Version 1.1 per investigator assessment) or death resulting from any cause.	4 years
Secondary	Part A: Objective Response Rate (ORR) in HRG High Participants	Key secondary efficacy endpoint: Objective response is defined as percentage of participants achieving complete response (CR) or partial response (PR); Denominator for percentages is the number of subjects with measurable disease in the full analysis set. The best overall response is the best response [in the order of CR, PR, stable disease (SD), and progressive disease (PD)] among all overall responses recorded from the start of treatment until the subject withdraws from the study. If there is no post-baseline tumor assessment or all post-baseline tumor assessments with overall response being Inevaluable captured in the CRF, the best overall response is classified as Inevaluable.	by trial termination (at 20 months)
Secondary	Part A: Objective Response Rate (ORR) in HRG Low Participants	Key secondary efficacy endpoint: Objective response is defined as percentage of participants achieving complete response or partial response; Denominator for percentages is the number of subjects with measurable disease in the full analysis set. The best overall response is the best response (in the order of CR, PR, SD, and PD) among all overall responses recorded from the start of treatment until the subject withdraws from the study. If there is no post-baseline tumor assessment or all post-baseline tumor assessments with overall response being Inevaluable captured in the CRF, the best overall response is classified as Inevaluable.	by trial termination (at 20 months)