A Phase 1 Dose Escalation and Expanded Cohort Study Of PF-06821497 In The Treatment Of Adult
Patients With Relapsed/Refractory Small Cell Lung Cancer (SCLC), Castration Resistant
Prostate Cancer (CRPC) And Follicular Lymphoma (FL).
This is an open label, multi center, Phase 1 dose escalation study of PF 06821497
administered orally as a single agent BID to patients with SCLC, CRPC, DLBCL and FL (Part
1A). For Part 1B (dose escalation monotherapy), PF 06821497 will be administered as
monotherapy in patients with FL. For Part 2A (dose escalation combination therapy), PF
06821497 will be administered in combination with SOC in patients with SCLC and CRPC. For
Part 2B (dose expansion), PF 06821497 will be administered in combination with SOC in
patients with SCLC and CRPC, and as monotherapy in patients with FL.
Part 1A (escalation monotherapy) will assess PF 06821497 administered as a single agent twice
daily in a continuous regimen to patients with advanced tumors (SCLC CRPC, DLBCL and FL). A
modified toxicity probability interval (mTPI) dose finding design will be applied in 2 4
patient cohorts. The starting dose of PF 06821497 will be 75 mg BID (DL1). Once the safety
and adequate target modulation has been established Parts 1B and 2A of the trial will be
initiated. Additional dose levels may be investigated, if adequate target inhibition has not
been achieved at DL3.
Part 1B [escalation recommended Phase 2 dose (RP2D) finding - monotherapy] will determine the
maximum tolerated dose (MTD) of monotherapy in FL (MTD1).
Part 2A (escalation RP2D finding -combination) will determine the MTD of the combination with
SOC in patients with SCLC (cisplatin or carboplatin with etoposide, MTD2, MTD3) and CRPC
(MTD4). Part 2B (dose expansion) will assess the efficacy of PF 06821497 at the RP2D
identified from the Part 2A, in combination with SOC in patients with SCLC (n=16 to 30 for
the 2 combination regimens), and CRPC (n=8 to 20) in addition to as a single agent twice
daily in patients with FL (n=8 to 20).
Key Inclusion Criteria:
Histological or cytological diagnosis of advanced / metastatic solid tumor with the
following tumor types in individual study parts:
-Histologically / cytologically confirmed advanced/unresectable or metastatic SCLC, CRPC,
DLBCL and FL that is refractory to or intolerable of standard treatment, or for which no
curative treatment is available. Note for FL (Parts 1A and 1B) during the dose finding
phase of study, follicular lymphoma patients must have exhausted all standard of care
Histologically confirmed FL patients that have exhausted all curative therapies and have
relapsed or refractory disease.
- Histologically or cytologically confirmed treatment naïve extensive disease SCLC
- Histologically confirmed FL patients that are intolerant of or resistant to standard
therapy or for which no curative therapy is available and have relapsed or refractory
disease (Part 2B).
- Histological / cytological diagnosis of castration resistant prostate cancer. Received
either abiraterone and/or enzalutamide treatment and has evidence of prostate cancer
progression (per PWG3):
- SCLC patients entering the study in the expansion cohort with at least one
measurable lesion as defined by Response Evaluation Criteria in Solid Tumors
(RECIST) version 1.1.
- FL patients entering the study in the expansion cohort with at least one
measurable lesion as defined by Response Evaluation Criteria in Lymphoma (RECIL)
- Females and/or male patients age 18 years.
- Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 or 1.
- Adequate Bone Marrow Function
- Adequate Renal Function
- Adequate Liver Function
- Serum pregnancy test (for females of childbearing potential) negative at
screening, and negative serum or urine pregnancy test at baseline prior to
- Known symptomatic brain metastases requiring steroids or CNS involvement in FL.
Previously diagnosed brain metastases are eligible if they have been treated and
recovered from the acute effects of radiation therapy or surgery prior to study entry,
have discontinued corticosteroid treatment for these metastases for at least 4 weeks
and are neurologically stable. Physiologic replacement doses of corticosteroids are
- At least 3 weeks since last major surgery (a lesser period is acceptable if decided to
be in the best interest of the SCLC patient).
- Treatment with more than 2gm acetaminophen per day within 14 days of study entry and
on study if required.
- Chronic liver diseases.
- History of alcohol abuse or binge drinking in the last 6 months prior to screening.
- Radiation therapy within 4 weeks prior to study entry. Note, patients who have
received radiotherapy must have recovered from any reversible side effects, such as
nausea and vomiting.
- Systemic anti cancer therapy - approved or investigational - within 4 weeks or 5
half-lives, whichever is shorter, prior to study entry, including antibody based
agents. Prostate cancer cohorts 2A and 2B must have not received more than 1 previous
regimen of systemic chemotherapy in mCPRC setting. SCLC cohorts must be chemotherapy
naive for SCLC however may have received one cycle of chemotherapy after discussion
with the sponsor.
- Last anti hormonal therapy within 2 weeks prior to C1D1.
- Prior stem cell transplant, autologous or allogenic, within 100 days prior to study
enrollment or patients who experienced graft veses host disease or who require
systemic immune suppressive therapy.
- Prior irradiation to >25% of the bone marrow.
- Active and clinically significant bacterial, fungal, or viral infection, including
hepatitis B virus (HBV), hepatitis C virus (HCV), known human immunodeficiency virus
(HIV) or acquired immunodeficiency syndrome (AIDS) related illness.
- Any of the following in the previous 6 months: myocardial infarction, congenital long
QT syndrome, Torsades de pointes, arrhythmias (including sustained ventricular
tachyarrhythmia and ventricular fibrillation), right bundle branch block and left
anterior hemiblock (bifascicular block), unstable angina, coronary/peripheral artery
bypass graft, symptomatic congestive heart failure (New York Heart Association class
III or IV), cerebrovascular accident, transient ischemic attack, or symptomatic
pulmonary embolism; ongoing cardiac dysrhythmias of NCI CTCAE Grade 2, atrial
fibrillation of any grade, or QTcF interval >480 msec at screening.
- Hypertension that cannot be controlled by medications (>150/100 mmHg despite optimal
- Known or suspected hypersensitivity to PF 06821497 or any components or enzalutamide
(CRPC) or platinum compound.
- Other acute or chronic medical or psychiatric condition, including recent (within the
past year) or active suicidal ideation or behavior or laboratory abnormality that may
increase the risk associated with study participation or investigational product
administration or may interfere with the interpretation of study results and, in the
judgment of the investigator, would make the patient inappropriate for entry into this
- Investigator site staff members directly involved in the conduct of the study and
their family members, site staff members otherwise supervised by the investigator, or
patients who are Pfizer employees, including their family members, directly involved
in the conduct of the study.
- Pregnant female patients; breastfeeding female patients; fertile male patients and
female patients of childbearing potential who are unwilling or unable to use 2 highly
effective methods of contraception as outlined in this protocol for the duration of
the study and for at least 28days after the last dose of investigational product.
- Active inflammatory gastrointestinal disease, chronic diarrhea, known diverticular
disease or previous gastric resection or lap band surgery. Gastroesophageal reflux
disease under treatment with proton pump inhibitors is allowed.
- Current use or anticipated need for food or drugs that are known strong CYP3A4/5
inhibitors, including their administration within 10 days or 5 half lives of the
CYP3A4/5 inhibitor, whichever is longer prior to first dose of investigational
- Current use or anticipated need for drugs that are known strong CYP3A4/5 inducers,
including their administration within 10 days or 5 half lives of the CYP3A4/5 inducer,
whichever is longer prior to the first dose of investigational product.