Patient case: 68-year-old male with non-small cell carcinoma; genetic feature: MET

Clinical trial: A Phase 1 Study of PT-112 Injection in Subjects With Advanced Solid Tumors

Summary: This is a Phase I, open-label, multi-center, non-randomized, dose-escalation study to be conducted in two parts: the Dose Escalation Phase and the Dose Confirmation Phase. The Dose Escalation Phase will determine the Maximum Tolerated Dose (MTD) and recommended Phase 2 dose(s) (RP2D) of PT-112 Injection and evaluate its safety and tolerability, PK (pharmacokinetic) and preliminary clinical effects. The Dose Confirmation Phase will be a cohort expansion at or below the MTD of PT-112 Injection. Subjects who tolerate the drug and who do not experience progressive disease may continue to receive PT-112 Injection at the discretion of the Principal Investigator for up to 6 cycles. For subjects who tolerate PT-112 Injection and who experience an objective response or stable disease through 6 cycles, the Sponsor will continue to provide PT-112 Injection under a separate mechanism, e.g., an extension protocol.

Detailed description: This is a Phase I, open-label, multi-center, non-randomized, dose-escalation study to be conducted in two parts: the Dose Escalation Phase and the Dose Confirmation Phase. The Dose Escalation Phase will determine the Maximum Tolerated Dose (MTD) and recommended Phase 2 dose(s) (RP2D) of PT-112 Injection and evaluate its safety and tolerability, PK (pharmacokinetic) and preliminary clinical effects. The Dose Confirmation Phase will be a cohort expansion at or below the MTD of PT-112 Injection. Subjects who tolerate the drug and who do not experience progressive disease may continue to receive PT-112 Injection at the discretion of the Principal Investigator for up to 6 cycles. For subjects who tolerate PT-112 Injection and who experience an objective response or stable disease through 6 cycles, the Sponsor will continue to provide PT-112 Injection under a separate mechanism, e.g., an extension protocol.

Eligibility: Key Inclusion Criteria:
  -  Pathologically confirmed advanced solid tumor for which standard therapy proven to provide clinical benefit does not exist or is no longer effective.
  -  Eastern Collaborative Oncology Group (ECOG) Performance Status of 0-1 (Appendix 1).
  -  Evaluable disease, either measurable on physical examination or imaging by Response Evaluation Criteria in Solid Tumors (RECIST v1.1, Appendix 2), or by informative tumor marker(s).
  -  Laboratory values at the Screening Visit:
  1. Absolute neutrophil count (ANC) ≥1,500/mm3;
  2. Platelets ≥100,000/mm3;
  3. Total bilirubin ≤1.5 × the upper limit of normal (ULN) (subjects with Gilbert's Syndrome are allowed if direct bilirubin is within normal limits);
  4. Aspartate aminotransferase (AST [SGOT]) ≤2.5 × the ULN;
  5. Alanine aminotransferase (ALT [SGPT]) ≤2.5 × the ULN;
  6. Serum albumin ≥3.0 gm/dL;
  7. Serum creatinine ≤1.5 mg/dL or a measured creatinine clearance ≥60 mL/min; and Negative serum β hCG (human chorionic gonadotropin) test in women of childbearing potential (defined as women ≤50 years of age, or >50 years of age with a history of amenorrhea for ≤12 months prior to study entry).
  -  Subjects with primary liver cancer or hepatic metastasis are eligible to enroll, provided that, at the Screening Visit, the following criteria are met:
  1. Total bilirubin is no higher than the ULN;
  2. AST and ALT are each ≤5 × the ULN;
  3. Severe liver dysfunction (Child-Pugh Class B or C) is not present; and
  4. Subjects with a history of esophageal bleeding have varices that have been sclerosed or banded and no bleeding episodes have occurred during the prior 6 months.
  -  If there is a known history of brain metastases, either treated with radiation therapy or untreated, the metastatic disease must be stable in the judgment of the Principal Investigator and must not require ongoing treatment with corticosteroids or anticonvulsants.
  -  Willing and able to provide written Informed Consent and comply with the requirements of the study.
  Key Exclusion Criteria:
  -  Any cytotoxic chemotherapy within 21 days prior to initiation of study drug.
  -  Any immunomodulatory drug therapy, anti-neoplastic hormonal therapy (unless dose has been stable for 3 months prior to Baseline and will remain stable during the trial), immunosuppressive therapy, corticosteroids >20 mg/day prednisone or equivalent, or growth factor treatment (e.g., erythropoietin) within 14 days prior to initiation of study drug.
  -  Presence of an acute or chronic toxicity of prior chemotherapy, with the exception of alopecia, that has not resolved to ≤Grade 1, as determined by National Cancer Institute Common Toxicity Criteria for Adverse Effects (CTCAE) v 4.0 (http://evs.nci.nih.gov/ftp1/CTCAE/About.html).
  -  Receipt of more than 3 prior regimens of cytotoxic chemotherapy for metastatic disease unless prior approval is granted by the Sponsor.
  -  Bone marrow reserve which, in the clinical judgment of the Principal Investigator, is not adequate for participation in this trial.
  -  Radiotherapy within 28 days prior to baseline.
  -  Receipt of radiotherapy to >25 % of bone marrow.
  -  Major surgery within 28 days prior to initiation of study drug.
  -  Life expectancy <12 weeks.
  -  Active bacterial, viral, or fungal infection requiring systemic therapy.
  -  Known human immunodeficiency virus or acquired immunodeficiency syndrome related illness.
  -  Clinically significant hearing impairment, as judged by the Principal Investigator.
  -  Uncontrolled congestive heart failure (New York Heart Association Classification 3 or 4), angina, myocardial infarction, cerebrovascular accident, coronary/peripheral artery bypass graft surgery, transient ischemic attack, or pulmonary embolism within 3 months prior to initiation of study drug.
  -  Unstable cardiac dysrhythmias or persistent prolongation of the corrected QT interval (QTc) (Fridericia) to >450 msec for males or >470 msec for females.
  -  Previous malignancy, except for non-squamous-cell carcinoma of skin or carcinoma in-situ of the uterine cervix, unless the tumor was treated with curative intent more than 2 years prior to study entry.

Relevance to patient case: not relevant