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Clinical Trial 19509

Cancer Type:
Interventions:Pegzilarginase; Pembrolizumab (Keytruda)

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

  • Jhanelle Gray

Call 813-745-6100
or 1-800-679-0775
Overview

Study Title

A Phase 1/2 Study Of Pegzilarginase (AEB1102, Co-Argi-PEG) In Combination With Pembrolizumab In The Treatment Of Patients With Extensive Disease (ED) Small Cell Lung Cancer (SCLC)

Summary

The main purpose of this Phase 1/2 study is to determine the safety and efficacy of pegzilarginase in combination with pembrolizumab in patients with ED-SCLC who have relapsed or progressive disease on or within 6 months of platinum-based chemotherapy.

Objective

Primary Objective: Phase 2: To determine (using a Simon 2-stage minimax design) the objective response rate (ORR: CR+PR) by RECIST 1.1 of pegzilarginase in combination with pembrolizumab. Secondary Objectives: * To determine the ORR by iRECIST 1.1 of pegzilarginase in combination with pembrolizumab. * To determine the following additional efficacy endpoints by both RECIST 1.1 and iRECIST: o Clinical benefit rate (CR + PR + SD lasting at least 8 weeks) o Time to response o Duration of response o Progression-free survival * To describe overall survival * To evaluate the safety profile of the combination of pegzilarginase with pembrolizumab in the study patient population (Phase 2)

Inclusion Criteria

> 1. Patient is > 18 years of age and able and willing to provide written informed consent

  • 2. Have histologically or cytologically confirmed SCLC that meets: Extensive disease per criteria of the International Association for the Study of Lung Cancer (IASLC)-American Joint Committee on Cancer (AJCC) TNM staging system.
  • 3. Have not tolerated or have progressed or relapsed on or within 6 months of platinum-based chemotherapy
  • 4. Have a performance status of ≤ 1 on the ECOG Performance Scale
  • 5. Have measurable disease based on RECIST 1.1
  • 6. Willing to undergo core needle or incisional biopsy to obtain fresh tumor tissue specimens
  • 7. Demonstrate adequate organ function as evidenced by laboratory testing.
  • 8. Female child-bearing potential must have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study medication
  • 9. Sexually active male or female must be surgically sterile post-menopausal, or must agree to use a physician-approved method of birth control during the study through a minimum of 120 days after the last study drug administration.

  • Exclusion Criteria

    > 1. Has received more than 2 platinum-based regimens against SCLC

  • 2. Has received pembrolizumab, or prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, or anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody as part of any previous therapy, including trials
  • 3. Has participated in Merck MK-3475 (pembrolizumab) clinical trials
  • 4. Has received pegzilarginase as part of any previous therapy
  • 5. Is currently participating in or has participated in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of treatment
  • 6. Has a diagnosis of immunodeficiency, is receiving systemic steroid therapy (except for physiological dose levels), or immunosuppressive therapies
  • 7. Has a known additional malignancy that is progressing or requires active treatment. Some exceptions may apply.
  • 8. Has known central nervous system (CNS) metastases. Patients with previously treated brain metastases may participate provided they are: a. Stable (without evidence of progression by imaging [using same imaging modality for each assessment] for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline) b. Have no evidence of new or enlarging brain metastases c. Are not using steroids for at least 7 days prior to trial treatment
  • 9. Has known carcinomatous meningitis
  • 10. Has an active autoimmune disease requiring systemic treatment in the past 2 years or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents. Some exceptions apply.
  • 11. Has evidence of interstitial lung disease, history of non-infectious pneumonitis that required steroids, or current pneumonitis.
  • 12. Inadequately controlled hypertension on more than one occasion in the month before planned day of infusion.
  • 13. Currently taking 3 or more anti-hypertensive medications.
  • 14. Prior history of hypertensive crisis or hypertensive encephalopathy.
  • 15. History of myocardial infarction, unstable angina, cardiac or other vascular stenting, angioplasty, or cardiac or vascular surgery within 6 months prior to day 1 of study treatment.
  • 16. Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.
  • 17. Has a known history of Human Immunodeficiency Virus (HIV) (positive for HIV p24 antigen or HIV 1/2 antibodies).
  • 18. Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).
  • 19. Has a known history of active tuberculosis (Bacillus tuberculosis).