LYT-200 Alone and in Combination With Chemotherapy or Tislelizumab in Patients With Locally Advanced or Metastatic Solid Tumors

NCT04666688 | Completed Phase 1 FDA Drug

• 1 other identifier: LYT-200-2020-01
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 12

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 Tislelizumab in Patients with Metastatic Solid Tumors

Conditions

Metastatic Cancer; Solid Tumor; Pancreatic Cancer; Urothelial Carcinoma; Head and Neck Cancer; Colorectal Cancer

Keywords

Metastatic cancer; Solid tumors; Combination therapy; Pancreatic cancer; Colon cancer; Bile duct cancer; Urothelial Carcinoma; Head and Neck Cancer; Colorectal Cancer

Outcome Measures

Primary Outcomes (3)

• Part 1: Incidence of Treatment-Emergent Adverse Events [Safety]

  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.

  approximately 1 year

• Part 1: Incidence of Dose Limiting Toxicities [Tolerability]

  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

  approximately 1 year

• Part 2: PFS or ORR [Preliminary Efficacy]

  PFS or ORR depending on tumor type

  approximately 1 year

Secondary Outcomes (4)

• Part 1: Pharmacokinetic (PK) profile of LYT-200: Maximum Plasma Concentration [Cmax]

  approximately 1 year

• Part 1: Pharmacokinetic (PK) profile of LYT-200: Time to Maximum Plasma Concentraton [Tmax]

  approximately 1 year

• Part 1: Pharmacokinetic (PK) profile of LYT-200: Area Under the Curve [AUC]

  approximately 1 year

• Part 1: Pharmacodynamics (PD) of LYT- 200

  approximately 1 year

Study Arms (3)

Part 1 single agent dose escalation

EXPERIMENTAL

LYT-200 in metastatic solid tumors

Drug: LYT-200

Part 1 combination agents dose expansion

EXPERIMENTAL

LYT-200 in combination with chemotherapy or Tislelizumab in select metastatic solid tumors

Drug: LYT-200; Drug: Tislelizumab; Drug: Gemcitabine/nab-paclitaxel

Part 2

EXPERIMENTAL

LYT-200 combination dose expansion in select metastatic solid tumors based on outcomes of Part 1

Drug: LYT-200; Drug: Tislelizumab; Drug: Gemcitabine/nab-paclitaxel

Interventions

LYT-200 DRUG

monoclonal antibody (mAb), targeting galectin-9 protein

Part 1 combination agents dose expansion; Part 1 single agent dose escalation; Part 2

Tislelizumab DRUG

anti-PD-1 monoclonal antibody

Part 1 combination agents dose expansion; Part 2

Gemcitabine/nab-paclitaxel DRUG

chemotherapy

Part 1 combination agents dose expansion; Part 2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Part 1
• Written Informed Consent (mentally competent patient, able to understand and willing to sign the informed consent form)
• Age ≥ 18 years, male or non-pregnant female
• Able to comply with the study protocol, as per Investigator's judgment
• Histologically confirmed, unresectable locally advanced or metastatic cancer. There are no limits to prior lines of therapies received for the treatment of the cancer condition for which the patient is being enrolled into this study.
• For the Part 1 combination urothelial carcinoma Cohorts 13 and 14: histologically or cytologically confirmed diagnosis of unresectable, locally advanced or metastatic urothelial carcinoma of the renal pelvis, ureter, bladder, or urethra (i.e., transitional cell carcinoma).
• For the Part 1 combination H/N cancer Cohorts 11 and 12: histologically confirmed, locally advanced or metastatic squamous cell carcinoma of head and neck (SCCHN; oral cavity, oropharynx, hypopharynx, or larynx).
• For urothelial and H/N combination cancer cohorts, prior exposure to immunotherapy is allowed, with standard of care treatment options and/or within a clinical trial context. If the patient received an anti-PD-1 and/or an anti-PD-L1 containing regimen at any point, they must have demonstrated at least stable disease, as per RECIST 1.1 or iRECIST criteria to one of these treatment regimens, if these measurements are available. If RECIST or iRECIST measurements are not available, then clinical PFS of at least 4 months is required to have been achieved on any of the prior anti-PD-1 and/or anti-PD-L1 containing regimens.
• There is no PD-L1 expression requirement for the Part 1 combination urothelial and H/N cohorts; however, fresh biopsy or archival tissue is required for assessment of PD-L1 by IHC, or a historical PD-L1 expression by IHC must be available. If PD-L1 expression data are already available, this does not override the protocol preference for obtaining a fresh biopsy whenever feasible.
• For Part 1 combination cohort H/N cancer patients of oropharynx origin: human papilloma virus (HPV) status needs to be established in the screening period or at any point while patient is on study drug, unless it is historically known. p16+ as a surrogate for HPV+, HPV RNA ISH or DNA PCR are all acceptable. The study accepts both HPV+ and HPV- patients.
• Life expectancy \> 3 months according to Investigator's judgment
• ECOG performance status 0-1
• Patient able and willing to undergo pre- and on/post treatment biopsies. According to the Investigator's judgment, 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.
• Measurable disease, according to RECIST v1.1. Note that lesions intended to be biopsied should not be target lesions.
• Adequate hematologic and end organ function, defined by the following laboratory results obtained prior to first dose of study drug treatment, provided no anticancer treatment was administered within the last 7 days:

You may not qualify if:

• Patient unwilling or unable to follow protocol requirements
• Patient diagnosed with metastatic cancer of an unknown primary
• Current illicit drug addiction (medical and recreational marijuana/cannabidiol \[CBD\]/ tetrahydrocannabinol \[THC\] would not be considered "illicit")
• Clinically significant, active uncontrolled bleeding, and any patients with a bleeding diathesis (e.g., active peptic ulcer disease). Prophylactic or therapeutic use of anticoagulants is allowed.
• Pregnant and/or lactating females
• Receiving any other investigational agents or participating in any other clinical trial involving another investigational agent for treatment of solid tumors within 3 weeks or 5 half-lives of the administered drug (whichever is shorter) prior to the first dose of study drug, or major surgery or planned surgery within 4 weeks of the first dose of study drug (this includes dental surgery).
• 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).
• Patients with fungating tumor masses
• History or current evidence of any condition, therapy, any active infections, or laboratory abnormality that might confound the results of the trial, interfere with the patient's participation for the full duration of the trial, or is not in the best interest of the patient to participate, in the opinion of the treating Investigator
• 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.
• History of other prior or other concomitant malignancy that requires other active treatment.
• Active parenchymal brain metastases, patients with carcinomatous meningitis 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
• 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
• 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
• Serious non-healing wound, active ulcer, or untreated bone fracture unless for e.g., a rib fracture for (which does not elicit treatment)

Sponsors & Collaborators

• PureTech: lead

Study Sites (12)

UCLA

Los Angeles, California, 90095, United States

Location

University of Colorado Hospital

Denver, Colorado, 80045, United States

Location

Sarah Cannon Research Institute at Health One

Denver, Colorado, 80218, United States

Location

Sarah Cannon Research Institute, Florida Cancer Specialists

Sarasota, Florida, 34232, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

South Texas Accelerated Research Therapeutics

Grand Rapids, Michigan, 49546, United States

Location

Columbia University

New York, New York, 10027, United States

Location

Memorial Sloan-Kettering Cancer Center

New York, New York, 10065, United States

Location

Sarah Cannon Research Institute, Tennessee Oncology

Nashville, Tennessee, 37203, United States

Location

University of Texas, M.D. Anderson Cancer Center

Houston, Texas, 77030, United States

Location

South Texas Accelerated Research Therapeutics

San Antonio, Texas, 78229, United States

Location

MeSH Terms

Conditions

Neoplasm Metastasis; Pancreatic Neoplasms; Carcinoma, Transitional Cell; Head and Neck Neoplasms; Colorectal Neoplasms; Colonic Neoplasms; Bile Duct Neoplasms

Interventions

tislelizumab

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Digestive System Neoplasms; Neoplasms by Site; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Intestinal Neoplasms; Gastrointestinal Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Biliary Tract Neoplasms; Bile Duct Diseases; Biliary Tract Diseases

Study Officials

• Aleksandra Filipovic, MD, Ph.D.

  PureTech Health

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Phase 1/2, two part, open-label study, which will enroll Part 1 and Part 2 sequentially. Part 1 is a single agent dose escalation design utilizing a continuous reassessment method (CRM) and a combination portion using a 4+2 study design. Part 2 is dose expansion into specific disease indications based on outcomes from Part 1.

Study Record Dates

• First Submitted: November 25, 2020
• First Posted: December 14, 2020
• Study Start: December 15, 2020
• Primary Completion: December 12, 2024
• Study Completion: December 12, 2024
• Last Updated: February 12, 2025

Record last verified: 2025-02

Locations

US (12)