Clinical Trial 18119

Cancer Type: Sarcoma
Interventions:G100; G305; LV305; cyclophosphamide; cytoxan (cyclophosphamide)

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

  • Mihaela Druta

Overview

Study Title

A Phase 1b Study Evaluating the Safety, Tolerability and Immunogenicity of CMB305 (Sequentially Administered LV305 and G305) in Patients with Locally Advanced, Relapsed, or Metastatic Cancer Expressing NY-ESO-1

Summary

Researchers want to find out if an investigational agent called CMB305 can help stimulate the body's immune system against NY-ESO-1 and the participant's tumor. The main purpose of this study is to see if the investigational agent is safe.

Objective

Primary: To evaluate the safety and tolerability of CMB305 (sequentially administered LV305 and G305) in patients with locally advanced, relapsed, or metastatic cancer expressing NY-ESO-1 Secondary/Exploratory: To evaluate clinical responses (by Immune-related Response Criteria (irRC) modified to use RECIST (v 1.1) measurement criteria), time to progression (TTP) and progression-free survival (PFS) as a preliminary assessment of clinical activity To evaluate the cellular and humoral immunogenicity of CMB305 in patients with locally advanced, relapsed, or metastatic cancer expressing NY-ESO-1 To evaluate pre- and post-regimen blood samples for potential biomarkers of immunogenicity and clinical tumor response To evaluate available pre- and post-regimen tumor tissue for histologic, immunohistologic, and genomic markers

Inclusion Criteria

  • Locally advanced, relapsed, and/or metastatic cancer with low or minimal tumor burden, which may or may not be measureable
  • Tumor histology consistent with one of the following: In Part 1, Dose Escalation - melanoma, non-small cell lung cancer (NSCLC), ovarian cancer (including fallopian tube carcinoma), or sarcoma (any subtype). In Part 2, Patient Expansion - NSCLC, ovarian cancer (including fallopian tube carcinoma), or selected sarcoma subtypes (synovial sarcoma or myxoid/round cell liposarcoma). At least one tumor must be accessible and participants must consent for biopsies in Arms C and D.
  • Tumor specimen positive for NY-ESO-1 expression by IHC and/or RT-PCR
  • If ovarian cancer, cancer antigen 125 (CA-125) must be ≥ 40 U/mL (unless patient has measureable disease that cannot be followed by CA-125); if melanoma, lactate dehydrogenase (LDH) must be ≤ upper limit of normal (ULN)
  • Inadequate response, relapse, and/or unacceptable toxicity with one or more prior systemic, surgical, or radiation cancer therapies, and for whom curative standard therapy is not an option (except patients with NSCLC who must have experienced either an inadequate response, relapse, and/or unacceptable toxicity with two or more prior systemic, surgical, or radiation cancer therapies)
  • ≥ 18 years of age
  • Life expectancy of ≥ 6 months per the investigator
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • Electrocardiogram (ECG) without evidence of clinically significant arrhythmia or ischemia
  • If female of childbearing potential (FCBP), willing to undergo pregnancy testing and agrees to use at least one highly effective or two effective contraceptive methods during the dosing period and for three months after last CMB305 injection
  • If male and sexually active with a FCBP, must agree to use highly effective contraception such as latex condom during the dosing period and for three months after last CMB305 injection

  • Exclusion Criteria

  • Investigational therapy within 3 weeks prior to CMB305 dosing
  • Prior administration of other NY-ESO-1-targeting immunotherapeutics
  • Significant immunosuppression from: a.) Concurrent, recent (≤ 4 weeks before dosing) or anticipated treatment with systemic corticosteroids at any dose, or, b.) Other immunosuppressive medications such as methotrexate, cyclosporine, azathioprine (antihistamines, non-steroidal anti-inflammatory drugs and aspirin permitted) or conditions such as common variable hypogammaglobulinemia or exposures such as large field radiotherapy.
  • Cancer therapies, including chemotherapy, radiation, biologics or kinase inhibitors, G-CSF or GM-CSF within 3 weeks prior to the first scheduled CMB305 dosing
  • Psychiatric, other medical illness or other condition that in the opinion of the principal investigator (PI) prevents compliance with study procedures or ability to provide valid informed consent
  • Significant autoimmune disease with the exception of alopecia, vitiligo, hypothyroidism or other conditions that have never been clinically active or were transient and have completely resolved and require no ongoing therapy
  • Myocardial infarction within 6 months of study initiation, active cardiac ischemia or New York Heart Association (NYHA) Grade III or IV heart failure
  • Inadequate organ function
  • History of other cancer within 3 years (except non-melanoma cutaneous malignancies and cervical carcinoma in situ).
  • Active tuberculosis or recent (> Uveal melanoma
  • Brain metastases considered unstable
  • Pregnant or nursing
  • Known allergy(ies) to any component of CMB305, or CPA.