Summary

for people ages 18 years and up (full criteria)
at UC Irvine
study started
estimated completion
Ignatius Ou(uci)

Description

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 in patients with solid tumors harboring an NRG1 fusion.

Official Title

A Phase I/II Study of MCLA-128, a Full Length IgG1 Bispecific Antibody Targeting HER2 and HER3, in Patients With Solid Tumors

Details

Study Design :

This open label (all participants know the identity of the study drug), multicenter (more than one study site), first-in-human study consisting of 2 parts. Part 1 is a dose escalation and Part 2 is a dose expansion cohort. Part 1 has been completed.

Part 2 new patient populations examined:

  • Group F: Patients with NSCLC with documented NRG1 fusion
  • Group G: Patients with pancreatic cancer with documented NRG1 fusion
  • Group H: Patients with any other solid tumor with documented NRG1 fusion

For these new patient populations, 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). For the new patient populations, overall response rate (ORR) and duration of response (DOR) will be described.

The study consists of 3 periods: Screening period (up to 28 days prior to the first dose of study drug); Treatment period (treatment cycles of 28 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 25 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 Additional sites may be added to ensure there is an acceptable enrollment rate or to replace non-enrolling/withdrawn sites.

Keywords

Solid Tumours Harboring NRG1 Fusion NSCLC Harboring NRG1 Fusion Pancreatic Cancer Harboring NRG1 Fusion NRG1 Fusion Bispecific Antibody IgG1, HER2, HER3 MCLA-128 Antibodies, Bispecific Immunologic Factors NRG1 Solid tumor Pancreatic cancer PDAC Non-small cell lung cancer NSCLC Pancreatic Neoplasms Antibodies Immunoglobulins

Eligibility

You can join if…

Open to people ages 18 years and up

  • At least one measurable lesion according to RECIST v1.1 OR evaluable disease for a limited number of patients (up to 10) in Group H;
  • 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;
  • Treatment with anti-cancer medication or investigational drugs within the following intervals before the first dose of MCLA-128:
  • >14 days or >5 half-lives prior to study entry, whichever is shorter.
  • >14 days for radiotherapy.
  • Recovery from major surgery or other complication to ≤ Grade 2 or baseline ;
  • Absolute neutrophil count ≥1.5 x 109/L without colony stimulating factor support;
  • Platelets ≥100 x 109/L;
  • Hemoglobin ≥8 g/dL or ≥2.2 mmol/L;
  • Alanine aminotransferase (ALT), aspartate aminotransferase (AST) ≤3 x upper limit of normal (ULN) and total bilirubin ≤1.5 x ULN; in cases of metastatic liver involvement, ALT/AST ≤5 x ULN and total bilirubin ≤2 x ULN will be allowed; in cases of antecedents of Gilbert's syndrome when total bilirubin ≤3.0 x ULN or direct bilirubin ≤1.5 x ULN will be allowed;
  • Estimated glomerular filtration rate (GFR) of >30 mL/min
  • Able to provide a tumor biopsy sample (fresh strongly preferred or else archival);
  • Not pregnant or nursing
  • Fertile patients must use effective contraception during and for 6 month after completion of study therapy;
  • Patients must have received prior standard therapy appropriate for their tumor type and stage of disease, or in the opinion of the Investigator, would be unlikely to tolerate or derive clinically meaningful benefit from appropriate standard of care therapy;
  • Locally-advanced unresectable or metastatic solid tumor malignancy with documented NRG1 gene fusion, identified through molecular assays such as PCR, next generation sequencing-based assays [DNA or RNA], or FISH as routinely performed at CLIA or other similarly-certified laboratories.

You CAN'T join if...

  • Pregnant or lactating;
  • Presence of an active uncontrolled infection or an unexplained fever;
  • Known hypersensitivity to any of the components of MCLA-128;
  • Known HIV, active Hepatitis B or Hepatitis C; patients treated for Hepatitis C and have undetectable viral loads are eligible
  • Known symptomatic or unstable brain metastases;
  • 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.

Locations

  • University of California Irvine not yet accepting patients
    Irvine California United States
  • Stanford University not yet accepting patients
    Palo Alto California United States

Lead Scientist

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Merus N.V.
ID
NCT02912949
Phase
Phase 1/2
Study Type
Interventional
Last Updated