Patient case: 73-year-old female with Pancreatic ductal adenocarcinoma. Genetic variant: ERBB3. Other conditions: Whipple, FNA.

Clinical trial: A Study of MCLA-128 in Patients With Solid Tumors

Summary: This is a Phase I/II, open-label, multi-center, multi-national, dose escalation, single agent study to assess the safety, tolerability, PK, PD, immunogenicity and anti-tumor activity of MCLA-128

Detailed description: Study Design :
  This open label (all participants know the identity of the study drug), multicenter (more than one study site), first-in-human study consists of 2 parts. Part 1 is a dose escalation and Part 2 is a dose expansion cohort. Part 1 has been completed.
  Part 2 patient populations of interest to receive the RP2D determined in Part 1 are:
  -  relapsed/refractory HER2-amplified breast cancer (Group A);
  -  advanced/metastatic epithelial ovarian cancer (Group C);
  -  advanced/metastatic HER2-amplified gastric cancer or esophageal-gastric junction adenocarcinoma (Group D); .
  -  advanced/metastatic endometrial cancer (Group E);
  -  advanced/metastatic or recurring HER2 expressing non small cell lung cancer (Group F);
  Part 2 will further characterize the safety and tolerability of the selected dose level of MCLA-128, as well as assessment of CBR, defined as the proportion of patients with a CR, PR or durable SD (SD for at least 12 weeks in duration).
  The study consists of 3 periods: Screening period (up to 28 days prior to the first dose of study drug); Treatment period (first dose of study drug until the last dose of study drug with treatment cycles of 21 days); and Follow Up period (through 30 days after the last dose and quarterly checks for survival data for up to 2 years). Participants' safety will be monitored throughout the study.
  Number of Sites:
  Up to 10 sites are estimated to be involved during Parts 1 and 2 of the study. Additional sites may be added to ensure there is an acceptable enrollment rate or to replace non-enrolling/withdrawn sites.

Eligibility: Inclusion Criteria:
  -  At least one measurable lesion according to RECIST v1.1;
  -  Performance status of ECOG 0 or 1;
  -  Estimated life expectancy of at least 12 weeks;
  -  Toxicities incurred as a result of previous anti-cancer therapy resolved to ≤Grade 1;
  -  At least a 4-week interval since last received radiotherapy;
  -  Recovery from major surgery;
  -  Absolute neutrophil count ≥1.5 x 109/L without colony stimulating factor support;
  -  Platelets ≥100 x 109/L;
  -  Hemoglobin ≥9 g/dL or ≥2.2 mmol/L (not transfusion dependent);
  -  Total bilirubin <1.5 times the upper limit of normal (ULN);
  -  AST (SGOT) ≤2.5 x ULN; ALT (SGPT) ≤2.5 x ULN; ≤5 x ULN for patients with advanced solid tumors with liver metastases; patients with confirmed bony metastases will be permitted on study with isolated elevations in ALP >5 x ULN;
  -  Serum creatinine ≤1.5 x ULN or estimated glomerular filtration rate (GFR) of >50 mL/min
  -  coagulation function (INR, and aPTT ≤1.5 x ULN , unless on therapeutic anticoagulants);
  -  Urine protein ≤ 2+ (as measured by dipstick) or ≤100 mg/24 hours urine
  -  Able to provide a tumor biopsy sample (preferably fresh or else archival); if archival: taken within 2 years from screening;
  -  Not pregnant or nursing
  -  Fertile patients must use effective contraception during and for 6 month after completion of study therapy;
  -  Patient with metastatic cancer who has disease progression after having received treatment with all available therapies known to convey clinical benefit
  Specific Inclusion Criteria for Part 2 (Group A) breast cancer (BC):
  -  Histologically-confirmed and documented advanced / metastatic BC, relapsed/refractory to at least 2 prior HER2 directed regimen for BC;
  -  Confirmed HER2 amplification based on historical pathology report or analysis of baseline fresh/archival tumor sample.
  Specific Inclusion Criteria for Part 2 (Group C) ovarian cancer (OC):
  -  Histologically-confirmed and documented advanced/metastatic epithelial OC for which no curative therapy is available;
  -  Prior therapy including all available standard therapies and at least 1 platinum based chemotherapy.
  Specific Inclusion Criteria for Part 2 (Group D) gastric or esophageal-gastric junction cancer (GC or GEC):
  -  Histologically-confirmed and documented advanced/metastatic GC or GEC ;
  -  Prior chemotherapy including platinum and fluoropyrimidine based treatment and trastuzumab
  -  Confirmed HER2 amplification based on historical pathology report or analysis of fresh/archival tumor sample.
  Specific Inclusion Criteria for Part 2 (Group E) endometrial cancer (EC):
  -  Histologically-confirmed and documented advanced/metastatic EC for which no curative therapy is available;
  -  Prior therapy including all available standard therapies and at least 1 prior chemotherapy.
  Specific Inclusion Criteria for Part 2 (Group F) Non small cell lung cancer (NSCLC):
  -  Histologically or cytologically documented diagnosis of Stage IIIB not amenable to radical treatment or Stage IV NSCLC; with pathological characterization of non-squamous or squamous histological subtype and adenocarcinoma subtype classification;
  -  Confirmed HER2 expression (by IHC) based on historical pathology report or analysis of baseline (fresh or archival) tumor sample;
  -  Prior treatment included all available standard therapies with at least one regimen of platinum-based chemotherapy in locally advanced/metastatic setting/recurrent NSCLC with documented disease progression by investigator assessment;
  -  Patients with ALK fusion oncogene with documented disease progression or intolerance with a first-line ALK Tyrosine Kinase Inhibitor (TKI) approved for the treatment of ALK fusion oncogene NSCLC;
  -  Patients with known mutation in the EGFR gene must have documented disease progression or intolerance with an EGFR TKI approved for the treatment of EGFR-mutant NSCLC.
  Exclusion Criteria:
  -  Pregnant or lactating;
  -  Presence of an active infection or an unexplained fever;
  -  Known hypersensitivity to any of the components of MCLA-128;
  -  Known HIV, Hepatitis B or Hepatitis C; patients treated for Hepatitis C and have undetectable viral loads are eligible
  -  Any untreated central nervous system lesion
  -  Patients with leptomeningeal metastases
  -  Presence of congestive heart failure or Left Ventricular Ejection Fraction<50% or history of significant cardiac disease, unstable angina, myocardial infarction or ventricular arrhythmia requiring medication.
  -  Previous or concurrent malignancy (excluding non-basal 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;
  -  Presence of any other medical or psychological condition deemed by the Investigator to be likely to interfere with a patient's ability to sign informed consent, cooperate or participate in the study, or interfere with the interpretation of the results.
  -  Prior anti-tumor therapy within 28 days prior to the first scheduled day of dosing with MCLA-128 unless a time interval equal to at least five half-lives of the investigational agent has passed;

Relevance to patient case: not relevant