We are updating the design of this site. Learn more.
Show more
ClinicalTrials.gov
ClinicalTrials.gov Menu

Ipilimumab With or Without Talimogene Laherparepvec in Unresected Melanoma

This study is ongoing, but not recruiting participants.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01740297
First Posted: December 4, 2012
Last Update Posted: October 9, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Amgen
Results First Submitted: August 23, 2017  
Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition: Melanoma
Interventions: Drug: Talimogene laherparepvec
Drug: Ipilimumab

  Participant Flow
  Hide Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations

This study was conducted at 33 centers in the United States of America, France, and Germany.

Particiants were enrolled in phase 1b from 07 February 2013 to 08 July 2013 and in phase 2 from 13 August 2013 to 25 February 2016.


Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
In phase 1b all participants received talimogene laherparepvec in combination with ipilimumab. In phase 2 participants were randomized 1:1 to receive talimogene laherparepvec plus ipilimumab or ipilimumab. Participants were stratified by disease stage and either v-raf murine sarcoma viral oncogene homolog B1 (BRAF) mutation V600E or prior therapy.

Reporting Groups
  Description
Phase 1b: Talimogene Laherparepvec + Ipilimumab Participants received talimogene laherparepvec at an initial dose of 10⁶ plaque-forming units (PFU)/mL injected into 1 or more skin, nodal, or subcutaneous tumors with maximum total volume of 4 mL. Subsequent doses of talimogene laherparepvec at 10⁸ PFU/mL (up to 4 mL total) began 3 weeks after the first dose and were administered every 2 weeks until complete response (CR), all injectable tumors had disappeared, confirmed disease progression per the modified immune-related response criteria (irRC), or intolerance of study treatment, whichever occurred first. Participants also received 3 mg/kg ipilimumab administered intravenously every 3 weeks for a total of 4 infusions starting at the time of the third dose of talimogene laherparepvec (week 6).
Phase 2: Ipilimumab Participants received ipilimumab 3 mg/kg intravenously every 3 weeks for a total of 4 infusions starting at week 1.
Phase 2: Talimogene Laherparepvec + Ipilimumab Participants received talimogene laherparepvec at an initial dose of 10⁶ PFU/mL injected into 1 or more skin, nodal, or subcutaneous tumors with a maximum total volume of 4 mL. Subsequent doses of talimogene laherparepvec at 10⁸ PFU/mL (up to 4 mL total) began 3 weeks after the first dose and were administered every 2 weeks until CR, all injectable tumors had disappeared, confirmed disease progression per the modified irRC, or intolerance of study treatment, whichever occurred first. Participants also received 3 mg/kg ipilimumab intravenously every 3 weeks for a total of 4 infusions starting at the time of the third dose of talimogene laherparepvec (week 6).

Participant Flow:   Overall Study
    Phase 1b: Talimogene Laherparepvec + Ipilimumab   Phase 2: Ipilimumab   Phase 2: Talimogene Laherparepvec + Ipilimumab
STARTED   19   100   98 
Received Talimogene Laherparepvec   19   0   95 
Received Ipilimumab   18   95   92 
COMPLETED   0   0   0 
NOT COMPLETED   19   100   98 
Continuing Study                10                67                68 
Withdrawal by Subject                1                9                11 
Death                8                23                19 
Sponsor Decision                0                1                0 



  Baseline Characteristics
  Hide Baseline Characteristics

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All enrolled participants

Reporting Groups
  Description
Phase 1b: Talimogene Laherparepvec + Ipilimumab Participants received talimogene laherparepvec at an initial dose of 10⁶ plaque-forming units (PFU)/mL injected into 1 or more skin, nodal, or subcutaneous tumors with maximum total volume of 4 mL. Subsequent doses of talimogene laherparepvec at 10⁸ PFU/mL (up to 4 mL total) began 3 weeks after the first dose and were administered every 2 weeks until complete response (CR), all injectable tumors had disappeared, confirmed disease progression per the modified immune-related response criteria (irRC), or intolerance of study treatment, whichever occurred first. Participants also received 3 mg/kg ipilimumab administered intravenously every 3 weeks for a total of 4 infusions starting at the time of the third dose of talimogene laherparepvec (week 6).
Phase 2: Ipilimumab Participants received ipilimumab 3 mg/kg intravenously every 3 weeks for a total of 4 infusions starting at week 1.
Phase 2: Talimogene Laherparepvec + Ipilimumab Participants received talimogene laherparepvec at an initial dose of 10⁶ PFU/mL injected into 1 or more skin, nodal, or subcutaneous tumors with a maximum total volume of 4 mL. Subsequent doses of talimogene laherparepvec at 10⁸ PFU/mL (up to 4 mL total) began 3 weeks after the first dose and were administered every 2 weeks until CR, all injectable tumors had disappeared, confirmed disease progression per the modified irRC, or intolerance of study treatment, whichever occurred first. Participants also received 3 mg/kg ipilimumab intravenously every 3 weeks for a total of 4 infusions starting at the time of the third dose of talimogene laherparepvec (week 6).
Total Total of all reporting groups

Baseline Measures
   Phase 1b: Talimogene Laherparepvec + Ipilimumab   Phase 2: Ipilimumab   Phase 2: Talimogene Laherparepvec + Ipilimumab   Total 
Overall Participants Analyzed 
[Units: Participants]
 19   100   98   217 
Age 
[Units: Years]
Mean (Standard Deviation)
 61.1  (12.1)   64.2  (13.3)   63.6  (14.0)   63.6  (13.5) 
Age, Customized 
[Units: Participants]
Count of Participants
       
< 65 years   11   54   46   111 
≥ 65 years   8   46   52   106 
Sex: Female, Male 
[Units: Participants]
Count of Participants
       
Female      11  57.9%      45  45.0%      36  36.7%      92  42.4% 
Male      8  42.1%      55  55.0%      62  63.3%      125  57.6% 
Ethnicity (NIH/OMB) 
[Units: Participants]
Count of Participants
       
Hispanic or Latino      1   5.3%      4   4.0%      0   0.0%      5   2.3% 
Not Hispanic or Latino      18  94.7%      96  96.0%      98 100.0%      212  97.7% 
Unknown or Not Reported      0   0.0%      0   0.0%      0   0.0%      0   0.0% 
Race/Ethnicity, Customized 
[Units: Participants]
       
American Indian or Alaska Native   0   1   0   1 
Asian   0   1   0   1 
Black (or African American)   0   3   0   3 
Multiple   0   1   1   2 
Native Hawaiian or Other Pacific Islander   0   0   0   0 
White   18   92   97   207 
Other   1   2   0   3 
Eastern Cooperative Oncology Group (ECOG) Performance Status [1] 
[Units: Participants]
       
0 (Fully active)   14   73   69   156 
1 (Restrictive but ambulatory)   5   27   29   61 
[1] Scale used to assess how a patient's disease is progressing, how the disease affects the daily living abilities of the patient: 0 = Fully active, able to carry on all pre-disease performance without restriction; 1 = Restricted in physically strenuous activity, ambulatory, able to carry out work of a light nature; 2 = Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about > 50% of waking hours; 3 = Capable of only limited self care, confined to a bed or chair > 50% of waking hours; 4 = Completely disabled, confined to bed or chair; 5 = Dead.
Tumor, Node, Metastasis (TNM) Disease Stage [1] 
[Units: Participants]
       
Stage IIIB - IVM1a   8   57   50   115 
Stage IVM1b/c   11   43   48   102 
[1] Stage IIIB: Ulcerated lesion and 1 lymph node or 2-3 nodes with micrometastasis, or any-depth lesion with no ulceration, and 1 lymph node or 2-3 nodes with macrometastasis; Stage IIIC: Ulcerated lesion and 1 lymph node with macrometastasis; 2-3 nodes with macrometastasis or ≥4 metastatic lymph nodes, matted lymph nodes, or in-transit met(s)/satellite(s); Stage IV: M1a: Spread to skin, subcutaneous tissue, or lymph nodes; normal lactate dehydrogenase (LDH) level; M1b: Spread to lungs, normal LDH; M1c: Spread to all other visceral organs, normal LDH or any distant disease with elevated LDH.
BRAF V600 Mutation Status [1] 
[Units: Participants]
       
Mutation   12   34   35   81 
Wild-type   7   60   62   129 
Missing/Unknown   0   6   1   7 
[1] Mutation status of v-raf murine sarcoma viral oncogene homolog B1 (BRAF) gene was based on a gene mutation that results in an amino acid substitution from valine (V) to glutamic acid (E) at codon 600 (V600E) and/or a substitution from valine to lysine (K) (V600K).


  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Phase 1b: Number of Participants With Dose-limiting Toxicities   [ Time Frame: The DLT evaluation period was 6 weeks from the initial administration of ipilimumab (week 6 to 12). ]

2.  Primary:   Phase 2: Objective Response Rate   [ Time Frame: Tumor response was assessed every 12 weeks until disease progression; median follow-up time was 57.7 weeks and 68.1 weeks in each treatment group respectively. ]

3.  Secondary:   Phase 1b: Objective Response Rate   [ Time Frame: Tumor response was assesed every 12 weeks until disease progression; median follow-up time was 148.4 weeks. ]

4.  Secondary:   Phase 2: Best Overall Response   [ Time Frame: Tumor response was assessed every 12 weeks until disease progression; median follow-up time was 57.7 weeks and 68.1 weeks in each treatment group respectively. ]

5.  Secondary:   Phase 2: Disease Control Rate   [ Time Frame: Tumor response was assessed every 12 weeks until disease progression; median follow-up time was 57.7 weeks and 68.1 weeks in each treatment group respectively. ]

6.  Secondary:   Phase 2: Durable Response Rate   [ Time Frame: Tumor response was assessed every 12 weeks until disease progression; median follow-up time was 57.7 weeks and 68.1 weeks in each treatment group respectively. ]

7.  Secondary:   Phase 2: Time to Response   [ Time Frame: Tumor response was assessed every 12 weeks until disease progression; median follow-up time was 57.7 weeks and 68.1 weeks in each treatment group respectively. ]

8.  Secondary:   Phase 2: Duration of Response   [ Time Frame: Tumor response was assessed every 12 weeks until disease progression; median follow-up time was 57.7 weeks and 68.1 weeks in each treatment group respectively. ]

9.  Secondary:   Phase 2: Progression-free Survival   [ Time Frame: From randomization until the data cut-off date of 23 August 2016; median follow-up time was 57.7 weeks and 68.1 weeks in each treatment group respectively. ]

10.  Secondary:   Phase 2: Resection Rate   [ Time Frame: From randomization until the data cut-off date of 23 August 2016; median follow-up time was 57.7 weeks and 68.1 weeks in each treatment group respectively. ]

11.  Secondary:   Phase 2: Overall Survival   [ Time Frame: From randomization until the data cut-off date of 23 August 2016; median follow-up time was 57.7 weeks and 68.1 weeks in each treatment group respectively. ]

12.  Secondary:   Phase 2: Kaplan-Meier Estimate of Percentage of Participants Alive at Month 12 and 24   [ Time Frame: Months 12 and 24; The median (Q1, Q3) follow-up time from randomization to the data cutoff date for the analysis was 80.6 (58.3, 106.3) weeks. ]

13.  Secondary:   Number of Participants With Adverse Events   [ Time Frame: From first dose of study treatment until 30 days after the last dose; median duration of treatment was 14.7, 9.1, and 21.1 weeks in each treatment group respectively. ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
  Hide Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.


  More Information
  Hide More Information

Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Study Director
Organization: Amgen Inc.
phone: 866-572-6436


Publications:

Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT01740297     History of Changes
Other Study ID Numbers: 20110264
2012-000307-32 ( EudraCT Number )
First Submitted: November 14, 2012
First Posted: December 4, 2012
Results First Submitted: August 23, 2017
Results First Posted: October 9, 2017
Last Update Posted: October 9, 2017