Study of IMC-11F8 in Patients With Advanced Solid Tumors

• Summary Listing of Participants Reporting Treatment-Emergent Adverse Events [ Time Frame: 10 months ] [ Designated as safety issue: Yes ]
• Maximum concentration (Cmax) [ Time Frame: 10 months ] [ Designated as safety issue: No ]
• Minimum concentration (Cmin) [ Time Frame: 10 months ] [ Designated as safety issue: No ]
• Area under the curve (AUC) [ Time Frame: 10 months ] [ Designated as safety issue: No ]
• Halflife (t½) [ Time Frame: 10 months ] [ Designated as safety issue: No ]
• Clearance (Cl) [ Time Frame: 10 months ] [ Designated as safety issue: No ]
• Steady-state volume of distribution (Vss) [ Time Frame: 10 months ] [ Designated as safety issue: No ]

• To establish the safety profile of IMC-11F8 [ Time Frame: 10 months ] [ Designated as safety issue: Yes ]
• To establish the Pharmacokinetic profile of IMC-11F8 in order to assess serum IMC-11F8 levels. [ Time Frame: 10 months ] [ Designated as safety issue: No ]
  The PK parameters of IMC-11F8 to be reported include maximal concentration (Cmax), area under the curve (AUC), halflife (t½), the clearance (Cl) and steady-state volume of distribution (Vss).
• Pharmacokinetic [ Time Frame: 10 months ] [ Designated as safety issue: No ]
  The PK parameters of IMC-11F8 to be reported include area under the curve (AUC).
• Pharmacokinetic [ Time Frame: 10 months ] [ Designated as safety issue: No ]
  The PK parameters of IMC-11F8 to be reported include halflife (t½).
• Pharmacokinetic [ Time Frame: 10 months ] [ Designated as safety issue: No ]
  The PK parameters of IMC-11F8 to be reported include the clearance (Cl).
• Pharmacokinetic [ Time Frame: 10 months ] [ Designated as safety issue: No ]
  The PK parameters of IMC-11F8 to be reported include steady-state volume of distribution (Vss).

This study is to establish the safety and pharmacokinetic (PK) profile of IMC-11F8, administered either: (1) in a 3-week cycle; or (2) in a 2-week cycle to Japanese patients with advanced solid tumors who have not responded to standard therapy or for whom no standard therapy is available.

This single center, open-label, single-arm, Phase 1 study will enroll 18 patients at a maximum. The actual size will vary depending on the dose-limiting toxicities (DLTs) observed and the resultant sizes of the cohorts. Patients will receive IMC-11F8 administered intravenously, once every 2 weeks or on Days 1 and 8 every 3 weeks for 6 weeks (one cycle). All infusions can be administered within ± 1 day of the scheduled administration date. After one cycle of treatment, patients who have an objective response or stable disease may continue to receive IMC-11F8 at the same dose and schedule until disease progression or other withdrawal criteria are met.

A minimum of three patients will be enrolled in each cohort. Dose escalation in successive cohorts will occur once all patients complete one cycle of therapy.

Patients will be enrolled sequentially into each cohort. A completed patient will be either a patient who completes the initial 6 week treatment period (Cycle 1) or a patient who discontinues therapy for an IMC-11F8-related toxicity during Cycle 1. Patients who do not complete the first 6 weeks of treatment for reasons other than an IMC-11F8-related toxicity will be replaced. Toxicity data for each cohort will be reviewed prior to dose escalation. Upon completion of all required safety evaluations during the initial 6 weeks, the next cohort of new patients will be treated at the next higher dose level using a dose escalation scheme.

• Biological: IMC-11F8
  IMC-11F8 600 mg intravenously, Days 1 and 8 every 3 weeks
  Other Name: necitumumab
• Biological: IMC-11F8
  IMC-11F8 800 mg intravenously, every 2 weeks.
  Other Name: necitumumab
• Biological: IMC-11F8
  IMC-11F8 800 mg intravenously, Days 1 and 8 every 3 weeks
  Other Name: necitumumab

• Experimental: Cohort 1
  Intervention: Biological: IMC-11F8
• Experimental: Cohort 2
  Intervention: Biological: IMC-11F8
• Experimental: Cohort 3
  Intervention: Biological: IMC-11F8

Inclusion Criteria:

• Solid tumor patient who has been histopathologically or cytologically documented
• Advanced primary or recurrent solid tumors patient who has not responded to standard therapy or for whom no standard therapy is available
• The patient has measurable or nonmeasurable lesions according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.0 guidelines
• The patient has an Eastern Cooperative Oncology Group performance status (ECOG PS) score of 0-1 at study entry
• The patient is able to provide written informed consent
• The patient is age 20 years or older
• The patient has a life expectancy of > 3 months
• The patient has adequate hematologic function
• The patient has adequate renal function
• The patient agrees to use adequate contraception for the duration of study participation and for at least 12 weeks after the last dose of study therapy
• The patient has adequate recovery from recent surgery, chemotherapy, and radiation therapy (including palliative radiation therapy). At least 28 days (6 weeks for nitrosoureas or mitomycin C) must have elapsed from major surgery, prior chemotherapy, prior treatment with an investigational agent or device, or prior radiation therapy. For treatment with nonapproved monoclonal antibodies, a minimum of 8 weeks must have elapsed
• The patient is willing to comply with study procedures until the End-of-Therapy visit

Exclusion Criteria:

• The patient has received chemotherapy or therapeutic radiotherapy within 28 days (6 weeks for nitrosoureas or mitomycin C) prior to entering the study, or the patient has ongoing side effects ≥ Grade 2 due to agents administered more than 28 days earlier (except alopecia)
• The patient has documented and/or symptomatic brain or leptomeningeal metastases (patients who are clinically stable [no symptoms during the 4 weeks prior to enrollment] with an assessment that no further treatment [radiation, surgical excision, or administration of steroids] is required are permitted to enter the study)

• The patient has an uncontrolled intercurrent illness including, but not limited to:

  • Ongoing or active infection requiring systemic antibiotic treatment
  • Congestive heart failure (Class III or IV per the New York Heart Association heart disease classification guidelines)
• The patient has participated in clinical studies of nonapproved experimental agents or procedures within 4 weeks prior to first dose of study therapy, or within 8 weeks prior to first dose of study therapy for nonapproved monoclonal antibodies
• The patient has received any previous treatment with monoclonal antibodies targeting the EGFR. Previous treatment with EGFR tyrosine kinase inhibitors, approved or nonapproved, is allowed. There must be a time interval of at least 4 weeks between the last EGFR TKI dose and the first dose of IMC-11F8
• The patient has acute or subacute intestinal occlusion/obstruction
• The patient has a history of inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis) requiring medical intervention in the three years prior to study entry
• The patient has acute pulmonary disorder, interstitial pneumonia, pulmonary fibrosis, or history thereof
• The patient has a known allergy to any of the treatment components, or to monoclonal antibodies or other therapeutic proteins such as fresh frozen plasma, human serum albumin, cytokines, or interleukins. In the event that there is suspicion that the patient may have allergies, the patient should be excluded
• The patient, if female, is pregnant (confirmed by urine or serum pregnancy test) or lactating
• The patient has known alcohol or drug dependency
• The patient is HBV antigen, HCV antibody, or HIV antibody positive
• The patient is assessed as inadequate for the study by the investigator