TT-816 As Monotherapy or in Combination with a PD-1 Inhibitor in Patients with Advanced Cancers (SEABEAM) (MK3475-E88)
- Conditions
- CancerAdvanced CancerAdvanced Solid TumorOncology
- Interventions
- Drug: A PD-1 inhibitor
- Registration Number
- NCT05525455
- Lead Sponsor
- Teon Therapeutics, Inc.
- 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.
- Detailed Description
This is an open-label, Phase 1/2, first-in-human (FIH), multiple ascending dose and dose-expansion study of TT-816 administered as monotherapy and in combination with a PD-1 inhibitor. Phase 1 will define the maximum tolerated dose (MTD) or recommended Phase 2 dose (RP2D) of TT-816 and of combination therapy that can be advanced to Phase 2. Phase 2 will define the preliminary efficacy of these regimens in the setting of advanced solid tumors with high unmet medical needs including Non-Small Cell Lung Cancer (NSCLC), Ovarian Cancer and Renal Cell Carcinoma (RCC).
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 9
Not provided
All patients, regardless of phase or cohort, who meet any of the following criteria will not be eligible for participation in the study:
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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.
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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.
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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.
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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.
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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.
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Patients previously enrolled on this study and received at least one dose of study drug.
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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.
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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.
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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.
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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.
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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.
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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.
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Have a history of (non-infectious) pneumonitis / interstitial lung disease that required steroids or has current pneumonitis / interstitial lung disease
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Have significant, uncontrolled, or active cardiovascular disease, including, but not restricted to:
- Myocardial infarction (MI) or unstable angina within 6 months before the first dose of study drug.
- History of an arterial thrombotic event, stroke, or transient ischemia attack within 12 months prior to first dose of study drug
- Symptomatic congestive heart failure (New York Heart Association classes II-IV) within 6 months before the first dose of study drug
- A cardiac arrhythmia that requires treatment within 6 months before the first dose of study drug
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Patients with evidence of an active infection requiring intravenous (IV) antibiotics within 7 days prior to the first dose of study drug.
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Patients with active uncontrolled bleeding, or a bleeding diathesis within 7 days prior to the first dose of study drug.
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Patients with serious or non-healing wound, fistula, skin ulcer, or non-healing bone fracture within 7 days prior to the first dose of study drug.
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Patients with known history of human immunodeficiency virus (HIV) infection. Note: No HIV testing is required unless patient history of HIV is unknown or if mandated by local health authority.
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Patients with a known history of Hepatitis B (defined as HBsAg reactive) or known active Hepatitis C virus infection (defined as HCV RNA [qualitative] is detected). Note: No testing for Hepatitis B and Hepatitis C is required unless patient history of Hepatitis B or Hepatitis C is unknown or if mandated by local health authority.
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Pregnant or breastfeeding or plans to become pregnant during the study.
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Patients unwilling or unable to follow protocol requirements, including any known psychiatric or substance use disorder that would interfere with the patient's ability to comply with the requirements of the study.
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Have a history or current evidence of any condition, therapy, or laboratory abnormality, or other circumstance that might confound the results of the study or interfere with the patient's participation for the full duration of the study, such that it is not in the best interest of the patient to participate, in the opinion of the Investigator.
There are no additional exclusionary criteria specific to participation in Phases 1m and 2m.
For Phases 1p and 2p, patients who meet any of the following criteria will not be eligible for participation in the study:
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Have severe hypersensitivity (≥ Grade 3) to pembrolizumab and/or any of its excipients.
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Have any history of radiation pneumonitis. Note: Patients must have recovered from all radiation-related toxicities and not require corticosteroids.
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Have received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA-4, OX 40, CD137), and was discontinued from that treatment due to an irAE.
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Have had an allogeneic tissue/solid organ transplant.
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For patients with NSCLC, have received radiation therapy to the lung that is >30Gy within 6 months of the first dose of trial treatment.
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Have an active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs).
Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Combination TT-816 plus a PD-1 inhibitor TT-816 Escalating doses followed by expansion targeting advanced cancers Combination TT-816 plus a PD-1 inhibitor A PD-1 inhibitor Escalating doses followed by expansion targeting advanced cancers Single agent TT-816 TT-816 Escalating doses followed by expansion targeting advanced cancers
- Primary Outcome Measures
Name Time Method Changes from baseline in clinical safety laboratory values and vital signs 2 years Changes from baseline in clinical safety laboratory values and vital signs
Efficacy assessments according to RECIST 1.1 (Phase 2) 3 years Overall Response Rate. Scale: confirmed Complete response (CR) or Partial response (PR), Duration of Response (DOR), and Disease Control Rate (DCR).
Incidence of adverse events (AEs) and serious adverse events (SAEs) - (Phase 1) 3 years 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
Incidence and nature of dose-limiting toxicities (DLTs) - (Phase 1) up to 21 days Incidence and nature of DLTs within a 3+3 trial design
MTD or RP2D of oral TT816 - (Phase 1m) 1 year The Maximum Tolerated Dose (MTD) or Recommended Phase 2 Dose (RP2D) of oral TT-816 as monotherapy (Phase 1m)
MTD or RP2D of oral TT816 - (Phase 1p) 1 year The Maximum Tolerated Dose (MTD) or Recommended Phase 2 Dose (RP2D) of oral TT-816 in combination with a PD-1 inhibitor (Phase 1p)
- Secondary Outcome Measures
Name Time Method Disease control rate (DCR) (Phase 1) 3 years Disease control rate (DCR)
PK (Cmax) of TT-816 - (Phase 1) 2 years Noncompartmental Pharmacokinetic (PK) parameters of TT-816 including the maximum plasma concentration (Cmax )
Progression-free survival (PFS) (Phase 1) 3 years Progression-free survival (PFS)
Objective response rate (ORR). - (Phase 1) 3 years Efficacy assessments according to RECIST 1.1. Objective Response Rate (ORR) Scale: Complete response (CR), Partial response (PR)
PK (Cmax) of TT-816 - (Phase 2) 2 years Noncompartmental PK parameters of TT-816 including the maximum plasma concentration (Cmax )
PK (AUC) of TT-816 - (Phase 2) 2 years Noncompartmental PK parameters of TT-816 including area under the plasma concentration-time curve (AUC)
Overall survival (OS) (Phase 1) 3 years Overall survival (OS).
Duration of response (DOR) (Phase 1) 3 years Duration of Response (DOR)
PK (AUC) of TT-816 - (Phase 1) 2 years Noncompartmental PK parameters of TT-816 including area under the plasma concentration-time curve (AUC)
Incidence of AESIs - (Phase 2) 3 years Incidence of AEs of special interest
Incidence of AEs and SAEs - (Phase 2) 3 years Incidence of AEs and SAEs graded according to the NCI CTCAE v5.0
PFS and OS - (Phase 2) 3 years Progression Free Survival (PFS) and Overall Survival (OS)
Trial Locations
- Locations (1)
Teon Investigational Site
🇺🇸Fairfax, Virginia, United States