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LYT-200 Alone and in Combination With Chemotherapy or Anti-PD-1 in Patients With Metastatic Solid Tumors

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ClinicalTrials.gov Identifier: NCT04666688
Recruitment Status : Recruiting
First Posted : December 14, 2020
Last Update Posted : April 6, 2021
Sponsor:
Information provided by (Responsible Party):
PureTech

Brief Summary:
A Phase 1/2 Open-label, Multi-center Study of the Safety, Pharmacokinetics, and Anti-tumor Activity of LYT-200 Alone and in Combination with Chemotherapy or Anti-PD-1 in Patients with Metastatic Solid Tumors

Condition or disease Intervention/treatment Phase
Metastatic Cancer Solid Tumor Cholangiocarcinoma Colorectal Cancer Pancreatic Cancer Drug: LYT-200 Drug: Anti-PD-1 Drug: Gemcitabine/nab-paclitaxel Phase 1 Phase 2

Detailed Description:

This is an open-label, uncontrolled, multicenter Phase 1/2 study with a dose escalation phase (Part 1) and a cohort expansion phase (Part 2) in patients with relapsed/refractory metastatic solid tumors.

Part 1: Dose Escalation Phase A dose-finding study will be conducted using a continuous reassessment method (CRM) to establish dose-limiting toxicities (DLTs) and the recommended Phase 2 dose (RP2D).

Part 2: Cohort Expansion Phase The second part of the protocol will adopt a Simon's two-stage optimal design. The Sponsor plans expansion cohorts for specific solid tumors, eg, pancreatic cancer, cholangiocarcinoma and/or potentially other solid tumor types based on results from part 1.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 250 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: Phase 1/2, two part, open-label study, which will enroll Part 1 and Part 2 sequentially. Part 1 is dose escalation utilizing a continuous reassessment method (CRM) and Part 2 is dose expansion into specific disease indications utilizing a Simon's Two Stage optimal design.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1/2 Open-label, Multi-center Study of the Safety, Pharmacokinetics, and Anti-tumor Activity of LYT-200 Alone and in Combination With Chemotherapy or Anti-PD-1 in Patients With Metastatic Solid Tumors
Actual Study Start Date : December 15, 2020
Estimated Primary Completion Date : December 2022
Estimated Study Completion Date : December 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Part 1 dose escalation
LYT-200 in metastatic solid tumors
Drug: LYT-200
monoclonal antibody (mAb), targeting galectin-9 protein

Experimental: Part 2 dose expansion
LYT-200 in select metastatic solid tumors, eg., pancreatic cancer, cholangiocarcinoma
Drug: LYT-200
monoclonal antibody (mAb), targeting galectin-9 protein

Drug: Anti-PD-1
anti-PD-1 monoclonal antibody

Drug: Gemcitabine/nab-paclitaxel
chemotherapy




Primary Outcome Measures :
  1. Part 1: Incidence of Treatment-Emergent Adverse Events [Safety] [ Time Frame: approximately 1 year ]
    Evaluation of safety parameters including treatment emergent adverse events as detected by hematology, chemistry, coagulation safety labs, physical exams, vital signs, ECG, ECHO/MUGA, ECOG status.

  2. Part 1: Incidence of Dose Limiting Toxicities [Tolerability] [ Time Frame: approximately 1 year ]
    Evaluation of tolerability parameters including dose limiting toxicities as detected by hematology, chemistry, coagulation safety labs, physical exams, vital signs, ECG, ECHO/MUGA, ECOG status

  3. Part 2: PFS or ORR [Preliminary Efficacy] [ Time Frame: approximately 1 year ]
    PFS or ORR depending on tumor type


Secondary Outcome Measures :
  1. Part 1 and 2: Pharmacokinetic (PK) profile of LYT-200: Maximum Plasma Concentration [Cmax] [ Time Frame: approximately 1 year ]
    To characterize Cmax of LYT- 200

  2. Part 1 and 2: Pharmacokinetic (PK) profile of LYT-200: Time to Maximum Plasma Concentraton [Tmax] [ Time Frame: approximately 1 year ]
    To characterize Tmax of LYT- 200

  3. Part 1 and 2: Pharmacokinetic (PK) profile of LYT-200: Area Under the Curve [AUC] [ Time Frame: approximately 1 year ]
    To characterize AUC of LYT- 200

  4. Part 1 and 2: Pharmacodynamics (PD) of LYT- 200: Immunophenotyping [ Time Frame: approximately 1 year ]
    Immunophenotyping of peripheral blood mononucleocyte samples and tumor tissue

  5. Part 1 and 2: Pharmacodynamics (PD) of LYT- 200: Cytokine profiling [ Time Frame: approximately 1 year ]
    cytokine profiling of serum samples

  6. Part 1 and 2: Pharmacodynamics (PD) of LYT- 200: Galectin-9 expression levels [ Time Frame: approximately 1 year ]
    Galectin-9 expression level detection in serum and tumor tissues

  7. Part 1 and 2: Pharmacodynamics (PD) of LYT- 200: Evaluation of Anti-drug Antibodies [ADA] [ Time Frame: approximately 1 year ]
    Immunogenicity of LYT- 200 detection by evaluating ADAs in serum samples



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Part 1 and Part 2

    1. Written Informed Consent (mentally competent patient, able to understand and willing to sign the informed consent form)
    2. Age ≥ 18 years, male or non-pregnant female
    3. Histologically confirmed unresectable metastatic cancer (adenocarcinomas and squamous cell carcinomas allowed). Patients with resectable disease are excluded
    4. Able to comply with the study protocol, as per Investigator's judgment
    5. Life expectancy > 3 months according to Investigator's judgement
    6. Eastern Cooperative Oncology Group (ECOG) performance status 0-1
    7. Coronavirus SARS-CoV-2 (COVID-19) negative patients.
    8. Patient able and willing to undergo pre- and on/post-treatment biopsies. According to the Investigator's judgement, the planned biopsies should not expose the patient to substantially increased risk of complications. Every effort will be made that the same lesion is biopsied on repeat biopsies. If the patient is eligible according to all other criteria but declines to consent to a biopsy or there are other medical reasons precluding biopsy, this will be discussed with the sponsor.
    9. Measurable disease, according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Note that lesions intended to be biopsied should not be target lesions.
    10. Adequate hematologic and end organ function, defined by the following laboratory results obtained prior to first dose of study drug treatment, provided no anti-cancer treatment was administered within the last 7 days:

      1. neutrophil count ≥ 1 x 109/L
      2. platelet count ≥ 100 x 109/L; for hepatocellular carcinoma (HCC) in Part 1 ≥ 50 x 109/L
      3. hemoglobin ≥ 9.0 g/dL without transfusion in the previous week
      4. creatinine ≤ 1.5 x upper limit of normal (ULN)
      5. aspartate aminotransferase AST (SGOT) ≤ 3 x ULN (≤ 5 x ULN when HCC or hepatic metastases are present)
      6. alanine aminotransferase (ALT [SGPT]) ≤ 3 x ULN (≤ 5 x ULN when HCC or hepatic metastases present)
      7. bilirubin ≤ 1.5 x ULN (patients with known Gilbert's disease may have a bilirubin ≤ 3.0 x ULN)
      8. albumin ≥ 3.0 g/dL
      9. international normalized ratio (INR) and partial thromboplastin time (PTT) ≤ 1.5 x ULN
      10. amylase and lipase ≤ 1.5 x ULN
    11. No evidence of active infection or infections requiring parenteral antibiotics, and no serious infection within 4 weeks before study start.
    12. Women of child-bearing potential must have a negative pregnancy test within 72 h prior to start of treatment. For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or to use contraceptive methods that result in a failure rate of < 1% per year during the treatment period and for at least 180 days after the last study treatment.

      A woman is of childbearing potential if she is post-menarche, has not reached a postmenopausal state (≥ 12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries and/or uterus).

      Examples of contraceptive methods with a failure rate of < 1% per year include bilateral tubal ligation, male sterilization, hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices and copper intrauterine devices. The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (eg, calendar, ovulation, symptom-thermal, or post ovulation methods) and withdrawal are not acceptable methods of contraception. Fertile men must practice effective contraceptive methods during the study, unless documentation of infertility exists.

    13. Four (4) weeks or 5 half-lives (whichever is shorter) since the last dose of anti-cancer therapy before the first LYT 200 administration
    14. Continuation of bisphosphonate treatment (eg, zoledronic acid) or denosumab for bone metastases, which have been stable for at least 6 months before C1D1, is allowed
    15. Biliary or gastric outlet obstruction allowed, provided it is effectively drained by endoscopic, operative, or interventional means
    16. Pancreatic, biliary, or enteric fistulae allowed, provided they are controlled with an appropriate non-infected and patent drain (if any drains or stents are in situ, patency needs to be confirmed before study start)

      Additionally, for Part 1 only:

    17. Patients:

      1. for whom there are no available standard of care options or
      2. who are not eligible for available and indicated standard of care therapy.

      Additionally, for Part 2 only:

    18. PDAC expansion cohort: 1st line metastatic patients who are either gemcitabine-containing regimen naïve or at least 3 months out of having been treated using a gemcitabine-containing regimen previously in a neoadjuvant or adjuvant/locally advanced setting
    19. CRC and CCA expansion cohorts - patients who have received at least one prior line of therapy in the metastatic setting

Exclusion Criteria

  1. Patient unwilling or unable to follow protocol requirements
  2. Patient diagnosed with metastatic cancer of an unknown primary
  3. Prior or current illicit drug addiction (medical and recreational marijuana/cannabidiol [CBD]/ tetrahydrocannabinol [THC] would not be considered "illicit")
  4. Clinically significant, active uncontrolled bleeding, and any patients with a bleeding diathesis (eg, active peptic ulcer disease). Prophylactic or therapeutic use of anticoagulants is allowed.
  5. Pregnant and/or lactating females
  6. Receiving any other investigational agents or participating in any other clinical trial involving another investigational agent for treatment of solid tumors within 4 weeks or 5 half-lives of the administered drug (whichever is shorter) prior to Cycle 1, Day 1 of the study, or other investigational therapy or major surgery within 4 weeks of the date of consent, or planned surgery within 4 weeks of envisaged study start (this includes dental surgery).
  7. Radiation therapy within 4 weeks of the first dose of study drug, except for palliative radiotherapy to a limited field, such as for the treatment of bone pain or a focally painful tumor mass, and which does not jeopardize required measurable lesions for response assessment (RECIST v1.1).
  8. Patients with fungating tumor masses
  9. Patients with locally advanced PDAC without distant organ metastatic deposits
  10. Grade 4 immune-mediated toxicities with a prior checkpoint inhibitor. Grade 2 or Grade 3 pneumonitis or any other Grade 3 checkpoint inhibitor-related toxicity that led to immunotherapy treatment discontinuation. Low-grade (< Grade 3) toxicities, such as neuropathy from prior treatments, manageable electrolyte abnormalities and lymphopenia, alopecia and vitiligo are allowed.
  11. History of second malignancy, except those treated with curative intent more than five years previously without relapse or low likelihood of recurrence (for example, non-melanotic skin cancer, cervical carcinoma in situ, early (or localized) prostate cancer, or superficial bladder cancer)
  12. Active brain or leptomeningeal metastases. Patients with brain metastases are eligible provided they have shown clinically and radiographically stable disease for at least 4 weeks after definitive therapy and have not used steroids (> 10 mg/day of prednisone or equivalent) for at least 4 weeks prior to the first dose of study drug
  13. Evidence of severe or uncontrolled systemic diseases, congestive heart failure > New York Heart Association (NYHA) class 2, myocardial infarction (MI) within 6 months, or laboratory finding that in the view of the Investigator makes it undesirable for the patient to participate in the trial
  14. Any medical condition that the Investigator considers significant to compromise the safety of the patient or that impairs the interpretation of LYT 200 toxicity assessment
  15. Serious non-healing wound, active ulcer, or untreated bone fracture
  16. Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures. For the purposes of this study, "recurrent" is defined as greater than or equal to 3 drains in the last 30 days.
  17. History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
  18. Significant vascular disease (eg, aortic aneurysm requiring surgical repair or recent arterial thrombosis) within 6 months of Cycle 1, Day 1
  19. History of pulmonary embolism, stroke or transient ischemic attack within 3 months prior to Cycle 1, Day 1
  20. History of abdominal fistula or gastrointestinal perforation within 6 months prior to Cycle 1, Day 1
  21. Active auto-immune disorder (except type I/II diabetes, hypothyroidism requiring only hormone replacement, vitiligo, psoriasis, or alopecia areata)
  22. Requires systemic immunosuppressive treatment, including, but not limited to cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor (anti-TNF) agents. Patients who have received or are receiving acute, low dose systemic immunosuppressant medications (eg, ≤ 10 mg/day of prednisone or equivalent) may be enrolled. Replacement therapy (eg, thyroxine, insulin, physiologic corticosteroid replacement therapy [eg, ≤ 10 mg/day of prednisone equivalent] for adrenal or pituitary insufficiency) is not considered a form of systemic treatment. The use of inhaled corticosteroids and mineralocorticoids (eg, fludrocortisone), topical steroids, intranasal steroids, intra-articular, and ophthalmic steroids is allowed.
  23. Severe tumor-related pain (Grade 3, Common Terminology Criteria for Adverse Events [CTCAE] v.5.0) unresponsive to broad analgesic interventions (oral and/or patches)
  24. Hypercalcemia(defined as greater than or equal to Grade 3, per CTCAE v 5.0)despite use of bisphosphonates
  25. Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the patient at high risk of treatment complications
  26. Received organ transplant(s)
  27. Patients undergoing dialysis
  28. For patients enrolled into nivolumab combination cohorts, no prior exposure to any anti-PD-1 or anti-PD-L1 agent in any prior lines of therapy. Additionally, patients diagnosed as dMMR/MSI-H are excluded.
  29. For Part 1, hormonal androgen deprivation therapy is allowed to continue for patients with metastatic castration-resistant prostate cancer.
  30. Any ablative therapy (Radio Frequency Ablation or Percutaneous Ethanol Injection) for HCC < 6 weeks prior trial entry
  31. Hepatic encephalopathy or severe liver adenoma
  32. Child-Pugh score ≥ 7

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04666688


Contacts
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Contact: Christopher Korth 617-982-2550 clinicaltrials@puretechhealth.com
Contact: Aleksandra Filipovic, MD, Ph.D. 617-982-2550 clinicaltrials@puretechhealth.com

Locations
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United States, Arizona
Mayo Clinic Recruiting
Phoenix, Arizona, United States, 85054
United States, Colorado
Sarah Cannon Research Institute at Health One Recruiting
Denver, Colorado, United States, 80218
United States, Florida
Mayo Clinic Florida Recruiting
Jacksonville, Florida, United States, 32224
Sarah Cannon Research Institute, Florida Cancer Specialists Recruiting
Sarasota, Florida, United States, 34232
United States, Michigan
South Texas Accelerated Research Therapeutics Recruiting
Grand Rapids, Michigan, United States, 49546
United States, Minnesota
Mayo Clinic Minnesota Recruiting
Rochester, Minnesota, United States, 55905
United States, Tennessee
Sarah Cannon Research Institute, Tennessee Oncology Recruiting
Nashville, Tennessee, United States, 37203
United States, Texas
University of Texas, M.D. Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
South Texas Accelerated Research Therapeutics Recruiting
San Antonio, Texas, United States, 78229
Sponsors and Collaborators
PureTech
Investigators
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Study Director: Aleksandra Filipovic, MD, Ph.D. PureTech Health
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Responsible Party: PureTech
ClinicalTrials.gov Identifier: NCT04666688    
Other Study ID Numbers: LYT-200-2020-01
First Posted: December 14, 2020    Key Record Dates
Last Update Posted: April 6, 2021
Last Verified: September 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by PureTech:
Metastatic cancer
Solid tumors
combination therapy
Pancreatic cancer
Cholangiocarcinoma
Colorectal cancer
Colon cancer
Bile duct cancer
Additional relevant MeSH terms:
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Colorectal Neoplasms
Pancreatic Neoplasms
Cholangiocarcinoma
Neoplasm Metastasis
Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Endocrine Gland Neoplasms
Pancreatic Diseases
Endocrine System Diseases
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplastic Processes
Pathologic Processes
Gemcitabine
Paclitaxel
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators