Study to Test the Safety and Tolerability of PF-07257876 in Participants with Selected Advanced Tumors

Overview

About this study

The purpose of this FIH study is to assess the safety and tolerability, effectiveness, pharnacokinetcs (PK), and pharmacodynamics (PD) of increasing dose levels of PF-07257876; to identify the MTD and potential RP2D of PF-07257876; and to select the RP2D for further studies in development. This study will enroll patients with advanced cancers with no curative therapy (NSCLC, SCCHN, and OvCa) whose tumors have either failed prior PD-1 or PD-L1 therapies (NSCLC or SCCHN); or platinum-based chemotherapy (OvCa). In addition, patients’ tumors must have demonstrated PD-L1 expression > 1%.

 

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria:

  • Participants ≥ 18 years old at the screening visit.
  • Histological or cytological diagnosis of advanced/metastatic NSCLC (regardless of subtype) or SCCHN meeting the following criteria:
    • Receipt of exactly 1 prior treatment regimen with a PD-1 or PD-L1 therapy, with or without chemotherapy (in combination or sequentially), in the advanced/metastatic disease setting;
    • No prior immunologic therapy may have been given other than anti-PD-1/PD-L1;
    • Prior chemotherapy is not required; participants may have received up to 2 prior chemotherapy regimens;
    • NSCLC Only: Most recent treatment must have included anti-PD-1/PD-L1 therapy;
    • Prior anti-PD-1/PD-L1 therapy must not have been permanently discontinued due to toxicity.
  • Confirmed radiographic progression of disease must have occurred within the following timeframes:
    • NSCLC: After at least 12 weeks of therapy, during which time the participant had a best response of either CR, PR, or SD (the SD must be >12 weeks). Note: Participants with “pseudo-progression” within this 12-week time period are eligible to enter the study. Pseudo-progression must be decided upon by the investigator, followed by a discussion with the sponsor;
    • SCCHN: After at least 6 weeks of therapy, during which time the participant had a best response of either CR, PR, or SD (SD must be > 6 weeks);
    • NSCLC Only: Confirmed radiographic disease progression must have occurred within < 12 weeks after the last dose of the anti-PD-1/PD-L1 therapy;
    • PD-L1 IHC positivity ≥1% (regardless of CoDx™ assays).
  • At least 1 measurable lesion, as defined by RECIST version 1.1, which has not been irradiated previously.
  • Ovarian cancer.
  • Histologically confirmed epithelial ovarian, fallopian tube, or peritoneal cancer, including malignant mixed Müllerian tumors with high-grade serous component.
  • Platinum-resistant/refractory disease, defined as disease progression within 6 months following the last administered dose of platinum therapy (resistant), or lack of response or disease progression while receiving the most recent platinum-based therapy (refractory), respectively.
  • May have received up to 3 lines of systemic anticancer therapy for platinum-sensitive disease, most recently platinum-containing, and no prior systemic therapy for platinum-resistant or refractory disease. (Note: Receipt of maintenance PARP inhibitor after platinum-containing therapy does not change this criteria). Prior therapy with chemotherapy + bevacizumab for platinum resistant disease is not required.
  • At least 1 measurable lesion, as defined by RECIST version 1.1, that has not been previously irradiated.
  • Must not have received prior anti-PD-1/PD-L1 therapy.
  • PD-L1 IHC positivity ≥ 1% (regardless of CoDx™ assays).
  • ECOG PS 0 or 1.
  • Estimated life expectancy of at least 3 months.
  • Adequate Bone Marrow Function, including:
    • ANC > 1,500/mm^3 or >1.5 x 10^9/L;
    • Platelets > 100,000/mm^3 or >100 x 10^9/L;
    • Hemoglobin >10 g/dL;
  • Adequate Renal Function including:
    • Estimated creatinine clearance ≥ 30 mL/min as calculated using the
      Cockroft-Gault method. In equivocal cases, a 24-hour urine collection test can
      be used to estimate the creatinine clearance more accurately.
  • Adequate Liver Function, including:
    • Total serum bilirubin < 1.5 x ULN;
    • AST and ALT < 2.5 x ULN;
    • < 5.0 x ULN if there is liver involvement by the tumor;
    •  Alkaline phosphatase < 2.5 x ULN (< 5 x ULN in case of bone metastasis).
  • Resolved acute effects of any prior therapy to baseline severity or CTCAE Grade ≤ 1 except for AEs not constituting a safety risk by investigator judgment.
  • Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures.
  • Participants in Part 1 must have recently obtained archival tumor tissue available (collected within 6 months prior to screening) for submission to the sponsor. Participants should have access to formalin-fixed paraffin embedded material containing tumor that is of diagnostic quality and representative of their diagnosed malignancy. If archival sample is older than 6 months, the patient must consent to undergo a de novo biopsy during the screening period. If a new biopsy represents a significant safety risk that can be documented specifically by the Investigator using medical reports, radiographs, or other materials that outline the exact risk involved, the patient may be considered for enrollment, after discussion of the risk with the sponsor.
  • Participants enrolled in the RP2D safety expansion cohort of Part 1 must have a tumor amenable to biopsy and consent to the mandatory paired de novo pretreatment and on-treatment biopsy procedures.
  • All participants in Part 2 must have a tumor amenable to biopsy and consent to undergo a de novo biopsy during screening. Participants entering the study in the subgroup(s) requiring mandatory on-treatment tumor biopsy must consent to these planned biopsy procedures.

Exclusion Criteria:

  • Participants with the finding of any new brain metastases detected by mandatory screening MRI are excluded. Participants may be re-screened for study entry under the following conditions:
    • if the Investigator deems their clinical status acceptable for participation in the trial;
    • all other inclusion and exclusion criteria are  satisfied;
    • corticosteroid treatment for these metastases has been discontinued for at least 4  weeks prior to study entry;
    • neurologically stable by examination and MRI for at least 3 months; 
    • do not require initiation or an increase in anti- epileptic medication for at least 4 weeks prior to start of study treatment; and
    • after discussion with the sponsor. 
    • Note: At the discretion of the sponsor based upon safety findings, screening and on-study MRIs may be removed for all participants during dose escalation.
  • Participants with at least one known brain metastasis larger than 4 cm in longest diameter, or with any known brain metastasis that is symptomatic.
  • Participants with previously diagnosed brain metastases are eligible if they have completed their treatment, recovered from the acute effects of radiation therapy or surgery prior to study entry (Day 1), and meet the following criteria
    • if the Investigator deems their clinical status acceptable for participation in the trial;
    • all other inclusion and exclusion criteria are satisfied;
    • corticosteroid treatment for these metastases has been discontinued for at least 4 weeks prior to study entry;
    • neurologically stable by examination and MRI for at least 3 months;
    • do not require initiation or an increase in anti-epileptic medication for at least 4 weeks prior to start of study treatment; and
    • after discussion with the sponsor.
  • Participants with abnormal neurologic examination by the investigator.
  • Participants with any other active malignancy within 3 years prior to enrollment, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ. Participants with a history of other curatively treated cancers may be eligible, after discussion and review by the sponsor.
  • Non-epithelial tumor or ovarian tumor with low malignant potential (i.e., borderline tumors).
  • Known or suspected hypersensitivity to PF-07257876 components.
  • Major surgery within 4 weeks prior to planned first dose.
  • Radiation therapy with treatment intent within 4 weeks prior to study entry. Any palliative radiation therapy must be completed within the 7 days prior to C1D1.
  • Irradiation to > 25% of the bone marrow.
  • Active bleeding disorder, including gastrointestinal bleeding, as evidenced by hematemesis, significant hemoptysis, or melena in the past 6 months.
  • History of Grade ≥ 3 immune-mediated AE (including AST/ALT elevations that where considered drug-related and CRS) that was considered related to prior immune modulatory therapy (e.g., immune CPIs, costimulatory agents, etc) and required immunosuppressive therapy. Participants with immune-mediated endocrinopathies controlled with hormonal replacement therapy (e.g., thyroid disorders, diabetes, adrenal insufficiency) are eligible.
  • History of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced pneumonitis, organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic
    organizing pneumonia), evidence of active pneumonitis on screening chest CT scan.
    • Note: A history of radiation pneumonitis (localized pulmonary fibrosis) in the field of prior radiation therapy is not exclusionary.
  • Other medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may increase the risk of study participation or, in the investigator’s judgment, make the participant inappropriate for the study.

Eligibility last updated 8/16/21. Questions regarding updates should be directed to the study team contact.

 

 

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Jacksonville, Fla.

Mayo Clinic principal investigator

Yujie Zhao, M.D., Ph.D.

Contact us for the latest status

Contact information:

Cancer Center Clinical Trials Referral Office

855-776-0015

Rochester, Minn.

Mayo Clinic principal investigator

Saravut Weroha, M.D., Ph.D.

Contact us for the latest status

Contact information:

Cancer Center Clinical Trials Referral Office

855-776-0015

Scottsdale/Phoenix, Ariz.

Mayo Clinic principal investigator

Panayiotis Savvides, M.D., Ph.D.

Open for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

855-776-0015

More information

Publications

Publications are currently not available
.
CLS-20523802

Mayo Clinic Footer