Clinical Trial 18395

Cancer Type: Malignant Hematology
Interventions:G100; Pembrolizumab (Keytruda)

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

  • Bela Kis

Overview

Study Title

Phase 1/2 Study Of Intratumoral G100 With Or Without Pembrolizumab In Patients With Follicular Non-Hodgkin's Lymphoma

Summary

In this trial, the safety, immunogenicity, and clinical efficacy of G100 will be examined alone or with pembrolizumab.

Objective

Primary: To evaluate the safety and tolerability of ascending doses of intratumoral G100 in patients with follicular non-Hodgkin's lymphoma (NHL) receiving local radiation. Secondary: To assess clinical responses by Immune-related Response Criteria (irRC) using bi-dimensional measurements and time to progression (TTP) as a preliminary indication of efficacy. To assess abscopal tumor responses in non-treated, distal tumor sites. To evaluate pre- and post-regimen tumor tissue and blood for exploratory biomarkers of immunologic and tumor response.

Inclusion Criteria

  • Follicular low-grade NHL: either treatment naïve or relapsed or refractory following at least one prior treatment. In Part 1 Dose Escalation only, in addition to follicular NHL, marginal zone B cell lymphomas: either treatment naïve or relapsed or refractory following at least one prior treatment.
  • Tumor mass(es) accessible for intratumoral injection and are being considered for local radiation therapy and at least one additional site of disease outside the radiation field for assessment of distal (abscopal) response.
  • ≥ 18 years of age.
  • Life expectancy of ≥ 6 months per the investigator.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
  • 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 3 months after last study treatment, or if receiving pembrolizumab, 4 months after last treatment.
  • 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 study treatment, or if receiving pembrolizumab, four months after last treatment.

  • Exclusion Criteria

  • Cancer therapies, including chemotherapy, radiation (non-study regimen related), biologics or kinase inhibitors, G-CSF or GM-CSF within 4 weeks prior to the first scheduled G100 dose.
  • Investigational therapy within 4 weeks prior to G100 dosing.
  • Prior administration of other intratumoral immunotherapeutics.
  • Inadequate organ function including: Marrow: Peripheral blood leukocyte count (WBC) 2.5 x Upper Limit of Normal (ULN), total serum bilirubin > 1.5 x ULN (patients with Gilbert's Disease may be included if their total bilirubin is ≤3.0 mg/dL); Renal: Creatinine > 1.5x ULN; Other: INR (prothrombin time ratio) or partial thromboplastin time (PTT) >1.5 x ULN.
  • Significant immunosuppression from: Concurrent, recent (≤ 4 weeks ago) or anticipated treatment with systemic corticosteroids at any dose, or; Other immunosuppressive medications such as methotrexate, cyclosporine, azathioprine or conditions such as common variable hypogammaglobulinemia.
  • Pregnant or nursing.
  • Myocardial infarction within 6 months of study initiation, active cardiac ischemia or New York Heart Association (NYHA) Grade III or IV heart failure.
  • History of other cancer within 2 years (except non-melanoma cutaneous malignancies and cervical carcinoma in situ).
  • Recent (> Central nervous system involvement with lymphoma, including parenchymal and leptomeningeal disease.
  • Significant autoimmune disease, including active non-infectious pneumonitis, 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.
  • Psychiatric, other medical illness or other condition that in the opinion of the PI prevents compliance with study procedures or ability to provide valid informed consent.
  • History of significant adverse or allergic reaction to any component of G100 including egg lecithin and, if enrolled in Part 2, anti-PD1 antibodies.
  • Use of anti-coagulant agents or history a significant bleeding diathesis. (If a superficial lymph node or subcutaneous mass is to be injected, patients on agents such as non-steroidal anti-inflammatory drugs (NSAIDs), aspirin, or clopidogrel are eligible and these agents do not have to be withheld. For procedures with moderate or significant risk of bleeding, long-acting agents such as aspirin or clopidogrel should be discussed with the Medical Monitor and may need to be discontinued before G100 therapy.
  • For participants enrolled in Part 2 with the potential to receive pembrolizumab: History of interstitial lung disease; Received a live virus vaccine within 30 days of planned study start; Has undergone prior allogeneic hematopoietic stem cell transplantation within the last 5 years (Potential participants who have had a transplant greater than 5 years ago are eligible as long as there are no symptoms of GVHD); Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or if the patient has previously participated in Merck MK-3475 clinical trials.