Patient case: 34-year-old female with melanoma; genetic feature: NRAS (Q61L)

Clinical trial: A Dose Escalation Study Of PF-06801591 In Melanoma, Head And Neck Cancer (SCCHN), Ovarian, Sarcoma, Hodgkin Lymphoma or Other Solid Tumors

Summary: Protocol B8011001 is a Phase 1, open-label, multi center, multiple-dose, dose escalation, safety, pharmacokinetics (PK), and pharmacodynamics (PD) study of PF-06801591 administered intravenously/subcutaneous in previously treated adult patients with locally advanced or metastatic melanoma, SCCHN, ovarian carcinoma, sarcoma, or relapsed or refractory cHL or other solid tumors. This 2 Part study will assess the safety and tolerability of increasing dose levels of intravenous (IV)/subcutaneous (SC) PF-06801591 and in Part 2 will establish the recommended Phase 2 dose (RP2D).

Detailed description: Protocol B8011001 is a Phase 1, open-label, multi center, multiple-dose, dose escalation, safety, PK, and PD study of PF-06801591 administered intravenously/subcutaneous in previously treated adult patients with locally advanced or metastatic melanoma, SCCHN, ovarian carcinoma, sarcoma, or relapsed or refractory cHL or other solid tumors.
  The first part of the study, Part 1 dose escalation, will assess the safety and tolerability of increasing dose levels of intravenous/subcutaneous PF-06801591 in patients with selected advanced or metastatic solid tumors in order to establish the maximum tolerated dose (MTD) using a modified Toxicity Probability Interval (mTPI) design. The second part of the study, Part 2 dose expansion, will expand enrollment to a restricted number of tumor types and doses based on the findings from Part 1 to establish the recommended Phase 2 dose (RP2D).

Eligibility: Inclusion Criteria:
  -  Performance status 0 or 1
  -  Histological or cytological diagnosis of locally advanced or metastatic melanoma, SCCHN, ovarian cancer, sarcoma, or relapsed or refractory cHL, or other solid tumors responsive to anti PD-1/PD-L1 therapy.
  -  Patient should have received at least 1 therapy for recurrent or metastatic disease, including both standards of care and investigational therapies.
  -  At least one measurable lesion as defined by RECIST version 1.1, or (for cHL) at least 1 fluordeoxyglucose positron emission tomography (FDG PET) avid (Deauville 4/5) measurable lesion >1.5 cm as defined by Response Criteria for Malignant Lymphoma that has not previously been irradiated.
  -  Adequate Renal, Liver, bone marrow function
  -  For Part 1B expansion cohorts: patient has consented to undergo a pre treatment and on treatment biopsy.
  Exclusion Criteria
  -  Active brain or leptomeningeal metastases.
  -  Ocular melanoma
  -  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 immunosuppressive treatment (e.g. prednisone > 10 mg equivalent daily), 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 allogenic bone marrow or hematopoietic stem cell transplant.
  -  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.
  -  Other potentially metastatic malignancy within past 5 years.
  -  For Part 2: prior treatment with a PD-1 or PD-L1 antibody.

Relevance to patient case: not relevant