Clinical Trial 18558

Cancer Type: Thoracic
Interventions:Avelumab; MSB00100718C (Avelumab); PD 0360324; PF-04518600; PF-05082566 (utomilumab)

Study Type: Treatment
Phase of Study: Phase I/II
Investigators:

  • Jhanelle Gray

Overview

Study Title

A Phase 1B/2 Open-Label Study to Evaluate Safety, Clinical Activity, Pharmacokinetics and Pharmacodynamics of Avelumab (MSB00100718C) in Combination with Other Cancer Immunotherapies in Patients with Advanced Malignancies

Summary

The purpose of this research study is to learn about the effects of the study treatment, avelumab/MSB0010718C when given with other cancer immunotherapies to find the best treatment combination for various cancer types. The study will begin by looking for the best dose of PF-05082566 in the combination.

Objective

Primary Objectives - Phase 1b lead-in: To assess safety and tolerability of avelumab in combination with increasing dose levels of other immune modulators in combination with a single dose level of avelumab in patients with advanced solid tumors in order to select the Recommended Phase 2 Dose(s) (RP2D)/schedule for the combination. Phase 2: To assess objective response (OR) of avelumab in combination with other immune modulators in patients with locally advanced or metastatic cancer [i.e., non-small cell lung cancer (NSCLC), melanoma, or squamous cell carcinoma of the head and neck(SCCHN)]. Secondary Objectives - To assess the overall safety and tolerability of avelumab and other immune modulators when given in combination; To characterize the pharmacokinetics of avelumab and other immune modulators when given in combination; To evaluate the immunogenicity of avelumab and other immune modulators when given in combination; To assess the antitumor activity of avelumab and other immune modulators when given in combination in patients with locally advanced or metastatic NSCLC, melanoma, and/or SCCHN; To evaluate candidate predictive biomarkers of sensitivity or resistance to avelumab in combination with other immune modulators in pre-treatment tumor tissue that may aid in the identification of patient subpopulations most likely to benefit from treatment.

Inclusion Criteria

  • Histological or cytological diagnosis of advanced/metastatic solid tumor. For Phase 1b, patients with non-small cell lung cancer (NSCLC) that have progressed on standard therapy or for which no standard therapy is available, and for Phase 2, patients with NSCLC (anaplastic lymphoma kinase (ALK)/epidermal growth factor receptor (EGFR) mutation negative), melanoma, and squamous cell carcinoma of the head and neck (SCCHN) with no restrictions for line of therapy. NSCLC patients in Phase 2 with tumor ALK or EGFR mutations must have received or been refractory/intolerant to standard therapy.
  • Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
  • Estimated life expectancy of at least 3 months
  • Adequate bone marrow, renal, and liver function
  • Resolved acute effects of prior therapy
  • Negative serum pregnancy test at screening
  • Males and females able to have children must agree to use 2 highly effective methods of contraception throughout the study and for at least 60 days after last dose
  • Signed and dated informed consent

  • Exclusion Criteria

  • Monoclonal antibody based anti-cancer therapy within 28 days prior to study entry or small -molecule based anti-cancer therapy (targeted therapy or chemotherapy) within 14 days prior to study entry.
  • Current or prior use of immunosuppressive medication within 7 days prior to study entry
  • Active autoimmune disease requiring systemic steroids or immunosuppressive agents within 7 days prior to study entry
  • Known prior or suspected hypersensitivity to investigational products
  • Major surgery within 4 weeks or radiation therapy within 14 days prior to study entry
  • Known symptomatic brain metastases requiring steroids
  • Previous high-dose chemotherapy requiring stem cell rescue
  • Prior allogeneic stem cell transplant or organ graft
  • Any of the following within 6 months prior to study entry: myocardial infarction, uncontrolled angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident, or transient ischemic attack
  • Symptomatic pulmonary embolism within 6 months prior to study entry
  • Known HIV or AIDS-related illness
  • Active infection requiring systemic therapy
  • Positive Hepatitis B Virus (HBV) or Hepatitis C Virus (HCV) test indicating acute or chronic infection
  • Administration of a live vaccine within 4 weeks prior to study entry
  • Diagnosis of other malignancy within 5 years, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ of the breast or cervix, or low-grade (Gleason ≤6) prostate cancer
  • Participation in other studies involving investigational drug(s) within 4 weeks prior to study entry and/or during study participation
  • Persisting toxicity related to prior therapy >Grade 1
  • Other severe acute or chronic medical condition, including colitis, inflammatory bowel disease, and pneumonitis or psychiatric condition, recent or active suicidal ideation or behavior, or end stage renal disease on hemodialysis, or laboratory abnormality that may increase the risk associated with study participation or investigational products administration or may interfere with the interpretation of results and, in the judgment of the Investigator, would make the patient inappropriate for study entry