A Study of TAVO412 in Patients with Cancer

NCT05548634 | Active Not Recruiting Phase 1 FDA Drug

• 1 other identifier: 59870003
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

TAVO412 Phase 1 is an open-label, non-randomized, 2-part Phase I study to examine the safety, tolerability, pharmacokinetics/pharmacodynamics, and preliminary efficacy of TAVO412. Part 1 will utilize a standard 3 + 3 design to determine the MTD/RP2D of TAVO412 in subjects with advanced or metastatic solid tumors who progressed on prior approved standard of care therapy. Part 2 will further evaluate the safety, tolerability, preliminary efficacy, pharmacokinetics (PK), and pharmacologic activity of TAVO412 in a new set of subjects with advanced or metastatic gastric cancer, non-small cell lung cancer (NSCLC), or subjects of other solid tumor types with best clinical responses (e.g., CR \> PR \> SD) from Part 1 that progressed on prior approved standard of care therapy.

Conditions

Cancer

Outcome Measures

Primary Outcomes (1)

• Safety and Tolerability of TAVO412 according to Adverse Events and Number of Participants With Dose Limiting Toxicity (DLT) using National Cancer Institute CTCAE v5.0

  According to the frequency, duration, and severity of Adverse Events (AEs). The Dose Limiting Toxicity (DLT) is based on drug related adverse events and includes unacceptable hematologic toxicity, non-hematologic toxicity of Grade 3 or higher, or elevations in hepatic enzymes suggestive of drug-induced liver injury. The Common Terminology Criteria for Adverse Events (CTCAE) v5.0 has a minimum value of Grade 1, or mild, and a maximum value of Grade 4, Life-threatening; pressor or ventilatory support indicated. All DLTs will be assessed by the investigator using National Cancer Institute CTCAE v5.0.

  Approximately 12 months

Secondary Outcomes (8)

• Maximum Serum Concentration (Cmax) of TAVO412

  Approximately 12 months

• Time to Reach Maximum Observed Serum Concentration (Tmax) of TAVO412

  Approximately 12 months

• Minimum Serum Concentration (Cmin) of TAVO412

  Approximately 12 months

• Area Under the Serum Concentration-Time Curve From 0-1 (AUC[t0-t1])

  Approximately 12 months

• Overall Response Rate (ORR)

  Approximately 12 months

Study Arms (7)

Part 1 Cohort 0

OTHER

IV infusion of TAVO412

Drug: TAVO412

Part 1 Cohort 1

OTHER

IV infusion of TAVO412

Drug: TAVO412

Part 1 Cohort 2

OTHER

IV infusion of TAVO412

Drug: TAVO412

Part 1 Cohort 3

OTHER

IV infusion of TAVO412

Drug: TAVO412

Part 1 Cohort 4

OTHER

IV infusion of TAVO412

Drug: TAVO412

Part 1 Cohort 5

OTHER

IV infusion of TAVO412

Drug: TAVO412

Part 2 Cohorts

OTHER

IV infusion of TAVO412

Drug: TAVO412

Interventions

TAVO412 DRUG

Biologic

Part 1 Cohort 0; Part 1 Cohort 1; Part 1 Cohort 2; Part 1 Cohort 3; Part 1 Cohort 4; Part 1 Cohort 5; Part 2 Cohorts

Eligibility Criteria

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

You may qualify if:

• Male/Female aged 18 (at the time of screening) or older.
• Willingness to provide written informed consent for the study.
• Locally relapsed or refractory disease; locally advanced disease must not be amenable to resection with curative intent.
• Subjects who have disease progression after treatment with available therapies that are known to confer clinical benefit, or who are intolerant to treatment, or who refuse standard treatment. There is no limit to the number of prior treatment regimens.
• Presence of measurable disease based on RECIST v1.1. Tumor lesions situated in a previously irradiated area, or in an area subjected to other locoregional therapy, are not considered measurable unless there has been demonstrated progression in the lesion.
• Part 1: Subjects with advanced or metastatic solid tumors who progressed, or refused, or are considered not eligible, on prior approved standard of care therapy. The following will also apply for Part 2 of the study.
• Patients with NSCLC who have sensitizing EGFR mutations must have experienced disease progression on prior EGFR TKIs while those with tumor cMET genomic alterations or over-expression must have received prior anti-PD1 agents and platinum-based chemotherapy either in combination or sequentially.
• Patients with gastric cancer or gastroesophageal cancer must have received prior cytotoxic chemotherapy and immune checkpoint inhibitor therapy, and where indicated, also received prior HER2-drected therapy or other FDA-approved targeted therapy.
• Patients with colorectal cancer must have received fluoropyrimidine, oxaliplatin, and irinotecan ± VEGF-targeting monoclonal antibodies as prior therapy. Patients with RAS-wild type tumors should have received approved anti-EGFR monoclonal antibody. Patients with MSI-high/dMMR colorectal cancer must have received prior immune checkpoint inhibitor therapy
• Patients with TNBC must have experienced disease progression on the following as prior therapies:
• Pembrolizumab plus chemotherapy (CPS ≥ 10%)
• Sacituzumab
• Trastuzumab-deruxtecan (HER2-low)
• Part 2: A new set of subjects with advanced or metastatic gastric cancer, non-small cell lung cancer (NSCLC), or subjects of other solid tumor types with best clinical responses (e.g., CR \> PR \> SD) from Part 1 that progressed on prior approved standard of care therapy.
• For subjects with Gastric Cancer: histologically confirmed Gastric or Gastro-Esophageal Junction Carcinoma (including adenocarcinoma arising from the lower esophagus). If multiple eligible patients exist, preference will be given to enroll subjects with cMet or EGFR mutations, over-expression, or gene amplification.

You may not qualify if:

• Laboratory and medical history parameters not within the protocol-defined range. If the screening laboratory tests below were conducted \> 7 days before treatment initiation, they will need to be repeated on Day 1 before initiation of treatment.
• Absolute neutrophil count \< 1.5 × 109/L.
• Platelets \< 100 × 109/L.
• Hemoglobin \< 9 g/dL or \< 5.6 mmol/L.
• Creatinine clearance \< 30 mL/minute (estimated by the Cockcroft-Gault formula, \[140 - age\] × body weight/plasma creatinine × 72 (× 0.85 if female)
• Aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase ≥ 2.5 × ULN.
• Note: Subjects with 1) bone metastases and 2) no hepatic parenchymal metastases on screening radiographic examinations may enroll if the alkaline phosphatase ≤ 5 × ULN. Subjects with 1) bone metastases and/or 2) hepatic parenchymal metastases on screening radiographic examinations may enroll if the alkaline phosphatase is ≤ 5 × ULN only with medical monitor approval.
• Total bilirubin ≥ 1.5 × ULN unless conjugated bilirubin ≤ ULN (note: conjugated bilirubin only needs to be tested if total bilirubin exceeds ULN). If there is no institutional ULN, then direct bilirubin must be \< 40% of total bilirubin.
• International normalized ratio, prothrombin time, or activated partial thromboplastin time \> 1.5 × ULN.
• Transfusion of blood products (including platelets or red blood cells) or administration of colony stimulating factors (including granulocyte colony-stimulating factor, granulocyte macrophage colony- stimulating factor, or recombinant erythropoietin) within 14 days before study Day 1.
• Receipt of anti-cancer medications or investigational drugs within the following intervals before the first administration of study drug:
• ≤ 14 days for chemotherapy, targeted small molecule therapy, or radiation therapy. Subjects must also not require chronic use of corticosteroids and must not have had radiation pneumonitis as a result of treatment. A 1-week washout is permitted for palliative radiation to non-central nervous system (CNS) disease with sponsor approval.
• Note: Bisphosphonates and denosumab are permitted concomitant medications.
• ≤ 28 days for prior immunotherapy or persistence of active cellular therapy (i.e., chimeric antigen receptor T-cell therapy; other cellular therapies must be discussed with medical monitor to determine eligibility).
• ≤ 28 days for a prior monoclonal antibody used for anticancer therapy with the exception of denosumab.

Sponsors & Collaborators

• Tavotek Biotherapeutics: lead

Study Sites (1)

Tisch Cancer Center

New York, New York, 10029, United States

Location

MeSH Terms

Conditions

Neoplasms

Study Officials

• Deborah Doroshow, MD

  MOUNT SINAI HOSPITAL

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: September 14, 2022
• First Posted: September 21, 2022
• Study Start: May 8, 2023
• Primary Completion: December 30, 2025
• Study Completion: June 1, 2026
• Last Updated: October 23, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)