A Phase 1/2 Study of CYT-0851 in B-Cell Malignancies and Advanced Solid Tumors

NCT03997968 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: CYT-0851-01
• Study Type: interventional
• Target: 169
• Locations: 1 country
• Sites: 16

Brief Summary

This clinical trial is an interventional, active-treatment, open-label, multi-center, Phase 1/2 study. The study objectives are to assess the safety, tolerability and pharmacokinetics (PK) of CYT-0851 in patients with relapsed/refractory B-cell malignancies and advanced solid tumors and to identify a recommended Phase 2 dose as a monotherapy and in combination with chemotherapy for evaluation in these patients.

Conditions

Malignancy; Non-hodgkin Lymphoma; Multiple Myeloma; Breast Cancer; Ovarian Cancer; Soft Tissue Sarcoma; Head and Neck Cancer; DLBCL; Mantle Cell Lymphoma; Follicular Lymphoma; Pancreatic Cancer; CLL; Small Cell Lung Cancer; Squamous Cell Carcinoma of Head and Neck; Triple Negative Breast Cancer

Keywords

Oral MCT-inhibitor; refractory; B-cell; solid tumor; cancer

Outcome Measures

Primary Outcomes (5)

• Part A: Incidence of dose limiting toxicity

  Cycle 1 Dose limiting toxicities and determination of the maximum tolerated dose

  28 Days

• Part B: Objective response rate

  clinical benefit as determined by investigator assessments of tumor response

  24 Weeks

• Part C: Incidence of dose limiting toxicity

  Cycle 1 Dose limiting toxicities and determination of the maximum tolerated dose in combination with rituximab and bendamustine

  28 Days

• Part D: Incidence of dose limiting toxicity

  Cycle 1 Dose limiting toxicities and determination of the maximum tolerated dose in combination with gemcitabine

  28 Days

• Part E: Incidence of dose limiting toxicity

  Cycle 1 Dose limiting toxicities and determination of the maximum tolerated dose in combination with capecitabine

  21 Days

Secondary Outcomes (18)

• Part A: Incidence of adverse events and other safety measures

  28 Days

• Part C: Incidence of adverse events and other safety measures

  28 Days

• Part D: Incidence of adverse events and other safety measures

  28 Days

• Part E: Incidence of adverse events and other safety measures

  21 Days

• Part A: Assessment of pharmacokinetic parameters

  Phase 1: 12 months

Study Arms (5)

CYT-0851 dose escalation

EXPERIMENTAL

Part A: CYT-0851 administered orally in rising doses QD or BID for 28 day cycles

Drug: CYT-0851

CYT-0851 dose expansion

EXPERIMENTAL

Part B: CYT-0851 administered orally at the selected Phase 2 dose for 28 day cycles

Drug: CYT-0851

CYT-0851 and rituximab and bendamustine

EXPERIMENTAL

Part C: Daily oral doses of CYT-0851 for 28 days in combination with rituximab on Day 1 and bendamustine on Days 1 and 2 of each 28 day cycle

Drug: CYT-0851; Drug: CYT-0851 in combination with rituximab and bendamustine

CYT-0851 and gemcitabine

EXPERIMENTAL

Part D: Daily oral doses of CYT-0851 for 28 days in combination with gemcitabine on Day 1, 8 and 15 of each 28 day cycle

Drug: CYT-0851; Drug: CYT-0851 in combination with gemcitabine

CYT-0851 and capecitabine

EXPERIMENTAL

Part E: Daily oral doses of CYT-0851 for 21 days in combination with capecitabine on Days to 14 of each 21 day cycle

Drug: CYT-0851; Drug: CYT-0851 in combination with capecitabine

Interventions

CYT-0851 DRUG

Part A and B: Daily oral doses of CYT-0851 for 28 day cycles

CYT-0851 and capecitabine; CYT-0851 and gemcitabine; CYT-0851 and rituximab and bendamustine; CYT-0851 dose escalation; CYT-0851 dose expansion

CYT-0851 in combination with gemcitabine DRUG

Part D: Daily oral doses of CYT-0851 for 28 days in combination with gemcitabine

CYT-0851 and gemcitabine

CYT-0851 in combination with capecitabine DRUG

Part E: Daily oral doses of CYT-0851 for 21 days in combination with capecitabine

CYT-0851 and capecitabine

CYT-0851 in combination with rituximab and bendamustine DRUG

Part C: Daily oral doses of CYT-0851 for 28 days in combination with rituximab and bendamustine

CYT-0851 and rituximab and bendamustine

Eligibility Criteria

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

You may qualify if:

• Male or female ≥18 years of age at time of informed consent.
• Female subjects of childbearing potential must be non-lactating, not pregnant as confirmed by a negative serum pregnancy test at most 30 days before enrollment and within 72 hours before the first administration of CYT-0851
• Female subjects of childbearing potential must not donate ova during the study and for at least 90 days after the last dose of study drug and must agree to continue using an effective method of contraception during the screening period to first study drug administration until 90 days after the last dose of study drug
• Male subjects who have not had a vasectomy must agree to use an effective method of contraception during the study and until 90 days after the last dose of the study drug, and to not donate sperm during the study and for at least 90 days after the last dose of study drug
• ECOG Performance Status of 0-1
• Measurable disease defined by disease-specific response criteria
• Histologically-proven B cell malignancies, meeting the following criteria:
• Relapsed, refractory B-cell non-Hodgkin lymphoma requiring therapy, after at least two prior therapies, and if transplanted, then at least 3-month post autologous stem cell transplant and if CART-treated, then evidence of progression no sooner than 3 months post CART treatment, or
• Relapsed, refractory chronic lymphocytic leukemia requiring therapy after at least two prior therapies, including BTK and BCL-2 inhibitor therapy (unless ineligible for such therapy), or
• For multiple myeloma, relapsed or progressive on or after treatment with at least three prior therapies that included a proteasome inhibitor, an imide, daratumumab, and if transplant eligible, a bone marrow transplant (unless unfit for transplant), or
• Histologically-proven solid tumor meeting the following criteria:
• Patients must have failed, refused, or not be eligible for further standard therapies (including chemotherapy, hormonal therapies, Her-2 directed therapies, as appropriate) expected to provide clinical benefit, and meeting the following criteria
• Metastatic breast cancer (including ER/PR positive or negative, Her-2 positive and negative, triple negative), treated with at least 1 prior therapy for metastatic disease, or
• Recurrent squamous cell carcinoma of the head and neck (HNSCC) (dose escalation) or human papilloma virus positive (HPV+) HNSCC (dose-escalation and backfill), treated with at least 1 prior therapy, or
• Ovarian cancer, progressive after treatment with at least prior platinum-based chemotherapy, and therapy with a PARP inhibitor or

You may not qualify if:

• Medical Conditions
• Known history of HIV
• Known history of viral hepatitis B unless HBV viral load is below the limit of quantification and off viral suppressive therapy
• Know history of hepatitis C unless antiviral treatment with curative intent completed and HCV viral load is below the limit of quantification.
• Myocardial infarction or stroke within 6 months
• Uncontrolled hypertension (systolic blood pressure (SBP) \> 160 or diastolic blood pressure (DBP) \>100 on maximal medical therapy)
• History of interstitial pulmonary disease
• Unresolved pneumonitis
• Grade ≥ 3 neuropathy
• Known active central nervous system (CNS) metastases. Subjects with previously treated CNS metastases may participate as long as clinically and radiologically stable for at least 4 weeks after treatment, have no evidence of new or enlarging lesions and are off steroids and asymptomatic for 28 days prior to dosing with study medication
• Known history of meningeal involvement or meningeal carcinomatosis
• Spinal cord compression not definitively treated with surgery and/or radiation, or previously diagnosed and treated spinal cord compression without evidence that disease has been clinically stable for \> 2 weeks prior to screening visit
• Presence of clinically significant cataracts
• Second malignancy, except treated basal cell or localized squamous skin carcinomas, localized prostate cancer, or other malignancy that is in remission or stable and for which patients have not been on active anti-cancer therapy for 2 years
• Pregnant or lactating. If β-HCG is elevated, eligible if ultrasound confirms absence of a pregnancy.

Sponsors & Collaborators

• Cyteir Therapeutics, Inc.: lead

Study Sites (16)

University of California San Francisco

San Francisco, California, 94158, United States

Location

Stanford Comprehensive Cancer Center

Stanford, California, 94305, United States

Location

Sarah Cannon Research Institute at HealthONE

Denver, Colorado, 80218, United States

Location

Florida Cancer Specialists and Research Institute

Sarasota, Florida, 34232, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

John Theurer Cancer Center at HUMC

Hackensack, New Jersey, 07601, United States

Location

NYU Langone Health

New York, New York, 10016, United States

Location

Oklahoma University-Stephenson Cancer Center

Oklahoma City, Oklahoma, 73104, United States

Location

Thomas Jefferson University, Sidney Kimmel Cancer Center

Philadelphia, Pennsylvania, 19107, United States

Location

Sarah Cannon Research Institute at Tennessee Oncology

Nashville, Tennessee, 37203, United States

Location

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

University of Washington Seattle Cancer Center

Seattle, Washington, 98109, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

MeSH Terms

Conditions

Neoplasms; Lymphoma, Non-Hodgkin; Multiple Myeloma; Breast Neoplasms; Ovarian Neoplasms; Sarcoma; Head and Neck Neoplasms; Lymphoma, Mantle-Cell; Lymphoma, Follicular; Pancreatic Neoplasms; Small Cell Lung Carcinoma; Squamous Cell Carcinoma of Head and Neck; Triple Negative Breast Neoplasms

Interventions

Gemcitabine; Capecitabine; Rituximab; Bendamustine Hydrochloride

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Neoplasms, Plasma Cell; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemorrhagic Disorders; Neoplasms by Site; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Neoplasms, Connective and Soft Tissue; Digestive System Neoplasms; Digestive System Diseases; Pancreatic Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Markus Renschler, MD

  Cyteir Therapeutics

  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

Study Record Dates

• First Submitted: June 24, 2019
• First Posted: June 25, 2019
• Study Start: October 9, 2019
• Primary Completion: November 30, 2024
• Study Completion: December 20, 2024
• Last Updated: December 24, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (16)