The ACTIVATE (Adoptive Cell Therapy InVigorated to Augment Tumor Eradication) Trial
ACTIVATE
Phase Ib Trial of Pembrolizumab Administered in Combination With or Following Adoptive Cell Therapy- A Multiple Cohort Study; The ACTIVATE (Adoptive Cell Therapy InVigorated to Augment Tumor Eradication) Trial
1 other identifier
interventional
8
1 country
1
Brief Summary
This is a phase 1b study for patients with metastatic (cancer has spread to various parts of the body) melanoma and ovarian cancer. The main purpose is to examine the safety and efficacy of administering pembrolizumab after receiving chemotherapy, tumor-infiltrating lymphocytes (TIL) and low dose interleukin 2 (IL-2). Patients will first receive either cyclophosphamide, or cyclophosphamide and fludarabine. These are chemotherapy agents that prepare the body to receive TILs. Patients are then infused with autologous TILs, a type of white blood cell that recognizes tumor cells and enters them, thereby causing tumor cells to break down. Following TILs infusion, patients will receive low-dose IL-2 therapy. This is a type of protein that is intended to activate and stimulate the growth of cells in the patient's immune system. If the patient meets the required criteria, they will be given pembrolizumab, a monoclonal antibody (drug made up of cloned immune cells) that is designed to block a protein called programed cell death ligand 1 (PD-L1) which will allow the body's immune system to kill the cancer cells.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_1
Started Jul 2017
Typical duration for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
May 9, 2017
CompletedFirst Posted
Study publicly available on registry
May 18, 2017
CompletedStudy Start
First participant enrolled
July 7, 2017
CompletedPrimary Completion
Last participant's last visit for primary outcome
August 4, 2020
CompletedStudy Completion
Last participant's last visit for all outcomes
August 4, 2020
CompletedAugust 14, 2020
August 1, 2020
3.1 years
May 9, 2017
August 12, 2020
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Monitoring of serious adverse events to determine the safety of initiating pembrolizumab following lymphodepleting chemotherapy, TIL administration, and low dose IL-2 injections within 35 days of TIL infusion.
Toxicities will be monitored on an ongoing basis. Severe adverse events will be reviewed for attribution to the study drug and whether they resolve to an acceptable grade within 35 days of TIL infusion. This information will be used to determine if the patient will go on to receive pembrolizumab. The regimen will be deemed feasible if at least 80% of patients enrolled go on to receive pembrolizumab.
2 years
Secondary Outcomes (3)
Overall Response Rate
2 years
Overall and Progression Free Survival
2 years
Safety profile of pembrolizumab therapy given after or in combination with ACT in patients with advanced melanoma and ovarian cancer using CTCAE v4.0
2 years
Study Arms (2)
Advanced metastatic melanoma (Cohort 1)
EXPERIMENTALCyclophosphamide and fludarabine followed by Tumor-Infiltrating Lymphocytes (TILs), Interleukin-2 (IL-2), and pembrolizumab
Advanced ovarian cancer (Cohort 2):
EXPERIMENTALCyclophosphamide followed by Tumor-Infiltrating Lymphocytes (TILs), Interleukin-2 (IL-2), and pembrolizumab
Interventions
Cohort 1: i.v., 60mg/kg per day for 2 days Cohort 2: i.v., 30mg/kg per day for 2 days
Cohort 1: i.v., 25mg/m2 per day for 5 days
Cohort 1 and 2: i.v., 200mg every 3 weeks
Cohort 1 and 2: i.v., 1x10\^10 - 1.6x10\^11 cells
Cohort 1 and 2: i.v., 125,000 IU/kg subcutaneous per day
Eligibility Criteria
You may qualify if:
- Be willing and able to provide written informed consent/assent for the trial.
- Be 18 years of age on day of signing informed consent.
- Have measurable disease based on RECIST 1.1.
- Have a performance status of 0 or 1 on the ECOG Performance Scale.
- Demonstrate adequate organ function, all screening labs should be performed within 10 days of treatment initiation.
- Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
- Female subjects of childbearing potential must be willing to use an adequate method of contraception - Contraception, for the course of the study through 6 months after the last dose of cyclophosphamide or fludarabine, or 120 days after last dose of pembrolizumab, whichever is longer.
- Male subjects of childbearing potential must agree to use an adequate method of contraception - Contraception, starting with the first dose of study therapy through 6 months after the last dose of cyclophosphamide or fludarabine, or 120 days after last dose of pembrolizumab, whichever is longer.
- Metastatic melanoma with surgically unresectable stage III or stage IV, histologically confirmed
- Previously treated with anti-PD-1 or anti-PD-L1 therapy (such as pembrolizumab or nivolumab) and experienced progression by RECIST v1.1
- Prior systemic anti-CTLA-4 therapy is allowed, provided that the first dose of pembrolizumab on study is administered more than 6 weeks after the last dose of anti-CTLA-4 treatment.
- Progression of disease by RECIST 1.1 within 3 months of last dose of therapy. If no alternative standard therapy is available, and there is evidence of clinical progression, subjects may proceed with TIL therapy after discussion with the Sponsor.
- Platinum resistant ovarian cancer, histologically confirmed
- Platinum resistant as defined by evidence of radiographic progression within 6 months of the last dose of platinum.
- Prior systemic anti-CTLA-4 therapy is allowed, provided that the first dose of pembrolizumab is administered more than 6 weeks after the last dose of anti-CTLA-4 treatment.
- +11 more criteria
You may not qualify if:
- Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment.
- Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
- Has a known history of active, untreated TB (Bacillus Tuberculosis)
- Hypersensitivity to pembrolizumab or any of its excipients.
- Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
- Has had prior chemotherapy within 28 days prior to study Day 1, or targeted small molecule therapy or radiation therapy within 14 days prior to study Day 1. Patients who have not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent.
- Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer, and in situ cervical cancer that has undergone potentially curative therapy.
- Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
- Has known history of, or any evidence of active, non-infectious pneumonitis.
- Has an active infection requiring systemic therapy.
- Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
- Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
- Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 6 months after last dose of cyclophosphamide or fludarabine or 120 days after the last dose of pembrolizumab.
- Has a known history of Human Immunodeficiency Virus (HIV) (e.g. HIV 1/2 antibody positive) or Human T-Cell Lymphotropic Virus (HTLV).
- Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA \[qualitative\] is detected).
- +8 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- University Health Network, Torontolead
- Merck Sharp & Dohme LLCcollaborator
Study Sites (1)
Princess Margaret Cancer Centre
Toronto, Ontario, M5G 2M9, Canada
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Marcus Butler, M.D.
Tumor Immunotherapy Program, Princess Margaret Cancer Centre
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
May 9, 2017
First Posted
May 18, 2017
Study Start
July 7, 2017
Primary Completion
August 4, 2020
Study Completion
August 4, 2020
Last Updated
August 14, 2020
Record last verified: 2020-08
Data Sharing
- IPD Sharing
- Will not share