MELANOMA Clinical Trial in Los Angeles CA
NCT02573259
| Phase 1
| Interventional
This study has recruited 147 Participants
Protocol B8011001 is a Phase 1, open-label, multi-center, multiple-dose, dose escalation and
expansion, safety, pharmacokinetics (PK), and pharmacodynamics (PD) study of PF-06801591 in
previously treated adult patients with locally advanced or metastatic melanoma, SCCHN,
ovarian carcinoma, sarcoma, NSCLC, urothelial carcinoma or other solid tumors. This is a 2
Part study whereby the safety and tolerability of increasing dose levels of intravenous (IV)
or subcutaneous (SC) PF-06801591 was assessed in Part 1. Part 2 expansion is designed to
further evaluate the safety and efficacy of SC PF-06801591 in patients with NSCLC or
urothelial carcinoma as well as confirm the recommended Phase 2 dose.
Details for the study
Brief Title
A Dose Escalation Study Of PF-06801591 In Melanoma, Head And Neck Cancer (SCCHN), Ovarian, Sarcoma, Non-Small Cell Lung Cancer, Urothelial Carcinoma or Other Solid Tumors
Official Title
A PHASE 1, OPEN-LABEL, DOSE ESCALATION AND EXPANSION STUDY OF PF-06801591 IN PATIENTS WITH LOCALLY ADVANCED OR METASTATIC MELANOMA, SQUAMOUS CELL HEAD AND NECK CANCER, OVARIAN CANCER, SARCOMA, NON-SMALL CELL LUNG CANCER, UROTHELIAL CARCINOMA OR OTHER SOLID TUMORS.
Brief Summary
Protocol B8011001 is a Phase 1, open-label, multi-center, multiple-dose, dose escalation and
<br /> expansion, safety, pharmacokinetics (PK), and pharmacodynamics (PD) study of PF-06801591 in
<br /> previously treated adult patients with locally advanced or metastatic melanoma, SCCHN,
<br /> ovarian carcinoma, sarcoma, NSCLC, urothelial carcinoma or other solid tumors. This is a 2
<br /> Part study whereby the safety and tolerability of increasing dose levels of intravenous (IV)
<br /> or subcutaneous (SC) PF-06801591 was assessed in Part 1. Part 2 expansion is designed to
<br /> further evaluate the safety and efficacy of SC PF-06801591 in patients with NSCLC or
<br /> urothelial carcinoma as well as confirm the recommended Phase 2 dose.
Detailed Description
Protocol B8011001 is a Phase 1, two part, open-label, multi center, multiple-dose, safety,
efficacy, PK, and PD study of PF-06801591 administered intravenously (IV) or subcutaneous
(SC) in previously treated adult patients with locally advanced or metastatic melanoma,
squamous cell carcinoma head and neck (SCCHN), ovarian carcinoma, sarcoma, non-small cell
lung carcinoma (NSCLC), urothelial carcinoma or other solid tumors.
The first part of the study, Part 1 dose escalation, was designed to assess the safety and
tolerability of increasing dose levels of IV or SC administered PF-06801591 to establish the
maximum tolerated dose (MTD) using a modified Toxicity Probability Interval (mTPI) design.
Part 2 expansion is designed to further evaluate the safety and efficacy of 300 mg of
PF-06801591 administered SC once every 4 weeks in patients with NSCLC or urothelial carcinoma
as well as confirm the recommended Phase 2 dose (RP2D). Part 1 enrollment has completed,
enrollment will only be allowed for Part 2.
Treatments and/or Procedures
PF 06801591
300 mg SC every 28 days (Part 1 and 2)
PF 06801591
IV every 21 days (Part 1)
Outcome Measures
Outcome measures are the tests that investigators perform to prove whether or not a treatment being tested in a clinical trial is having any effect.
Primary
Overall Safety Profile
Type, incidence, severity, timing, seriousness and relationship to study treatment of adverse events (AE) and any laboratory abnormalities.
Primary
Estimate clinical efficacy
Objective tumor response, as assessed using the Response Evaluation Criteria in Solid Tumor (RECIST) version 1.1 criteria, immune-related RECIST (irRECIST).
Primary
Percentage of participants with Dose-limiting toxicities (DLT)
A DLT is any of a predefined set of unacceptable adverse events that are observed and that are at least possibly related to the investigational agent(s) OR a DLT is any of a predefined set of unacceptable adverse events (AE), regardless of cause.
Secondary
Area under the concentration versus time curve (AUCt)
AUCt will be calculated for PF- 06801591
Secondary
Incidence of anti drug antibodies (ADA)
Incidence of anti drug antibodies (ADA) and neutralizing antibodies (NAb) against PF-06801591.
Secondary
Percentage of Receptor Occupancy (RO)
Percentage RO of PF-06801591 in circulating T cells over time following PF-06801591 administration.
Secondary
Maximum Observed Plasma Concentration (Cmax)
Cmax will be calculated for PF-06801591
Secondary
Evaluate overall survival
Median time to death, proportion of patients alive at 6 months, 1 year, and 2 years.
Secondary
Evaluate preliminary anti-tumor activity of PF-06801591
Time to event endpoints based on RECIST and irRECIST, including time to response (TTR) and time to progression (TTP) as well as progression free survival (PFS) and immune-related (ir) PFS (irPFS) as appropriate, duration of stable disease (DOSD) and irDOSD as appropriate, and duration of response (DOR) and irDOR as appropriate.
Study Criteria
Inclusion Criteria (Part 2 Only):
- Histological or cytological diagnosis of locally advanced or metastatic NSCLC or
urothelial carcinoma who have progressed on or were intolerant to standard of care
systemic therapy, or for whom standard of care systemic therapy was refused (refusal
must be documented) or unavailable.
- No prior treatment with anti-PD-1 or anti-PD-L1 therapy.
- NSCLC patients whose tumor is not known to have ALK or EGFR mutations must have
progressed on or after no more than 1 prior line of platinum-containing systemic
therapy or were intolerant or refused standard of care systemic therapy.
- NSCLC patients whose tumor is known to have ALK or EGFR mutation must have received
prior systemic therapies that only include 1 or more lines of ALK or EGFR targeting
drugs and chemotherapy limited to 1 line of a platinum-based regimen and they must
have progressed on or after both types of therapies.
- Urothelial carcinoma patients must have received up to 2 lines of prior systemic
therapy and progressed on or after, experienced disease recurrence within 12 months of
neoadjuvant or adjuvant treatment, were intolerant to, ineligible or refused
platinum-containing systemic therapy. If urothelial cancer patients are treatment
naïve and eligible for platinum-containing systemic therapy but are refusing platinum
chemotherapy, they must also be documented to have previous PD-L1 high status.
- Provide archived tumor tissue sample taken within the past 2 years or provide a fresh
tumor biopsy sample.
- At least one measurable lesion as defined by RECIST version 1.1.
- Adequate renal, liver, thyroid and bone marrow function.
- Performance status 0 or 1.
- Patient is capable of receiving study treatment for at least 8 weeks.
Exclusion Criteria (Part 2 Only)
- Active brain or leptomeningeal metastases.
- Active, known or suspected autoimmune disease. Patients with vitiligo, type I diabetes
mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone
replacement, psoriasis not requiring systemic treatment, or conditions not expected to
recur in the absence of an external trigger are permitted to enroll. Diagnosis of
prior immunodeficiency or organ transplant requiring immunosuppressive therapy or
prior allogeneic bone marrow or hematopoietic stem cell transplant.
- Patients with a condition requiring systemic treatment with either corticosteroids
(>10mg daily prednisone equivalents) or other immunosuppressive medications within 14
days of study drug administration. Inhaled or topical steroids, and adrenal
replacement doses >10 mg daily prednisone equivalents are permitted in the absence of
active autoimmune disease.
- Patients with a history of interstitial lung disease, non-infectious pneumonitis, or
active pulmonary tuberculosis. Those with active lung infections requiring treatment
are also excluded.
- History of Grade ≥3 immune mediated AE (including AST/ALT elevations that where
considered drug related and cytokine release syndrome) that was considered related to
prior immune modulatory therapy (eg, immune checkpoint inhibitors, co-stimulatory
agents, etc.) and required immunosuppressive therapy.
- Active hepatitis B or C, HIV/AIDS.
- Other potentially metastatic malignancy within past 5 years.