TT-816 As Monotherapy or in Combination with a PD-1 Inhibitor in Patients with Advanced Cancers (SEABEAM) (MK3475-E88)

NCT05525455 | Terminated Phase 1 FDA Drug

• 1 other identifier: SEABEAM
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 5

Brief Summary

A first-in-human study using TT-816 as a single agent and in combination with a PD-1 inhibitor in advanced cancers.

Conditions

Advanced Cancer; Advanced Solid Tumor; Cancer; Oncology

Outcome Measures

Primary Outcomes (6)

• Incidence of adverse events (AEs) and serious adverse events (SAEs) - (Phase 1)

  Incidence of adverse events (AEs) and serious adverse events (SAEs) graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0

  3 years

• Incidence and nature of dose-limiting toxicities (DLTs) - (Phase 1)

  Incidence and nature of DLTs within a 3+3 trial design

  up to 21 days

• Changes from baseline in clinical safety laboratory values and vital signs

  Changes from baseline in clinical safety laboratory values and vital signs

  2 years

• MTD or RP2D of oral TT816 - (Phase 1m)

  The Maximum Tolerated Dose (MTD) or Recommended Phase 2 Dose (RP2D) of oral TT-816 as monotherapy (Phase 1m)

  1 year

• MTD or RP2D of oral TT816 - (Phase 1p)

  The Maximum Tolerated Dose (MTD) or Recommended Phase 2 Dose (RP2D) of oral TT-816 in combination with a PD-1 inhibitor (Phase 1p)

  1 year

• Efficacy assessments according to RECIST 1.1 (Phase 2)

  Overall Response Rate. Scale: confirmed Complete response (CR) or Partial response (PR), Duration of Response (DOR), and Disease Control Rate (DCR).

  3 years

Secondary Outcomes (12)

• Objective response rate (ORR). - (Phase 1)

  3 years

• Disease control rate (DCR) (Phase 1)

  3 years

• Duration of response (DOR) (Phase 1)

  3 years

• Progression-free survival (PFS) (Phase 1)

  3 years

• Overall survival (OS) (Phase 1)

  3 years

Other Outcomes (8)

• Food effects on PK parameters (Phase 2)

  2 years

• Molecular analysis of patient tissue (Phase 1 and Phase 2)

  2 years

• Molecular analysis of patient tissue (Phase 1 and Phase 2)

  2 years

Study Arms (2)

Single agent TT-816

EXPERIMENTAL

Escalating doses followed by expansion targeting advanced cancers

Drug: TT-816

Combination TT-816 plus a PD-1 inhibitor

EXPERIMENTAL

Escalating doses followed by expansion targeting advanced cancers

Drug: TT-816; Drug: A PD-1 inhibitor

Interventions

TT-816 DRUG

TT-816 is a novel, oral cannabinoid CB2 receptor antagonist acting as an immune checkpoint inhibitor for the treatment of a broad range of solid tumors

Combination TT-816 plus a PD-1 inhibitor; Single agent TT-816

A PD-1 inhibitor DRUG

Programmed death receptor-1 (PD 1)-blocking antibody

Combination TT-816 plus a PD-1 inhibitor

Eligibility Criteria

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

You may not qualify if:

• All patients, regardless of phase or cohort, who meet any of the following criteria will not be eligible for participation in the study:
• Received another systemic anticancer therapy including investigational agents within 4 weeks or 5 half-lives (whichever is shorter) prior to the first dose of study drug. Note: Patients must have recovered from all AEs due to previous therapies to ≤ Grade 1 or baseline. Patients with ≤ Grade 2 neuropathy may be eligible. Patients with endocrine-related AEs ≤ Grade 2 requiring treatment or hormone replacement may be eligible.
• Received radiotherapy within 2 weeks prior to the first dose of study drug or palliative radiation therapy within 1 week prior to the first dose of study drug.
• Have another primary malignancy that is progressing, has required active treatment within the last 3 years, or has not been treated with curative intent within the last 3 years (discuss with Medical Monitor). Patients with carcinoma-in-situ that has been treated successfully more than 3 years prior to screening, non-metastatic cutaneous basal cell or squamous cell carcinoma, or non-muscle invasive bladder cancer are not excluded.
• Have untreated central nervous system (CNS), epidural tumor or metastasis, or brain metastasis. Patients with previously treated brain metastases may participate provided they are radiologically stable, i.e., without evidence of progression for at least 4 weeks by repeat imaging (repeat MRI or CT with contrast should be performed during study screening), clinically stable, and without requirement of steroid treatment for at least 14 days prior to first dose of study treatment.
• Major surgical procedures within 4 weeks (28 days) of the first dose of study drug. If the patient had major surgery, the patient must have recovered adequately from the procedure and/or any complications from the surgery prior to starting study drug.
• Patients previously enrolled on this study and received at least one dose of study drug.
• Is currently participating in or has participated in a study of an investigational agent or therapy, or has used an implantable investigational device within 4 weeks prior to the first dose of study treatment. Note: Patients who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks after the last dose of the previous investigational agent.
• Have a QT interval corrected (QTc) prolongation to \> 470 milliseconds (ms) at screening based on a 12-lead electrocardiogram (ECG) in triplicate using the Fridericia formula (QTcF): QTc = QT / RR 1/3.
• Patients on concomitant medications that increase or possibly increase the risk of QTc prolongation and/or induce Torsades de Pointes, including antifungals, antibiotics, antipsychotics, antiemetics, antiarrhythmics, and antineoplastic medications.
• Patients on proton pump inhibitors (PPIs) who cannot switch to H2 inhibitors (or cannot stop PPI therapy entirely) at least 3 days before their first dose of TT-816 study drug for the duration of the study. See protocol Section 5.2 for permissible usage of H2 inhibitors during the study.
• Have received a live or live-attenuated vaccine within 30 days prior to the first dose of study intervention. Administration of killed vaccines are allowed.
• Have a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study drug.
• Have a history of (non-infectious) pneumonitis / interstitial lung disease that required steroids or has current pneumonitis / interstitial lung disease
• Have significant, uncontrolled, or active cardiovascular disease, including, but not restricted to:

Sponsors & Collaborators

• Teon Therapeutics, Inc.: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (5)

Teon Investigational Site

Nashville, Tennessee, 37203, United States

Location

Teon Investigational Site

Austin, Texas, 78758, United States

Location

Teon Investigational Site

San Antonio, Texas, 78229, United States

Location

Teon Investigational Site

West Valley City, Utah, 84119, United States

Location

Teon Investigational Site

Fairfax, Virginia, 22031, United States

Location

MeSH Terms

Conditions

Neoplasms

Study Officials

• Teon Clinical Development

  Teon Therapeutics, Inc.

  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: Multiple ascending dose and dose-expansion of TT-816 administered as a single agent or in combination with a PD-1 inhibitor.

Study Record Dates

• First Submitted: August 22, 2022
• First Posted: September 1, 2022
• Study Start: August 29, 2022
• Primary Completion: September 7, 2023
• Study Completion: September 7, 2023
• Last Updated: November 21, 2024

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (5)