A Study of TAVO412 in Patients with Cancer (TAVO412)

NCT06761651 | Recruiting Phase 1 DMC

• 1 other identifier: 59870005
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 6

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

Keywords

TAVO412

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 Cohort1

OTHER

150mg bi-weekly IV infusion of TAVO412

Drug: TAVO412

Part 1 Cohort2

OTHER

375mg bi-weekly IV infusion of TAVO412

Drug: TAVO412

Part 1 Cohort3

OTHER

750mg bi-weekly IV infusion of TAVO412

Drug: TAVO412

Part 1 Cohort4

OTHER

1125mg bi-weekly IV infusion of TAVO412

Drug: TAVO412

Part 1 Cohort5

OTHER

1500mg bi-weekly IV infusion of TAVO412

Drug: TAVO412

Part 2 Cohorts

OTHER

RP2D IV infusion of TAVO412

Drug: TAVO412

Part 1 Cohort6

OTHER

1750mg bi-weekly IV infusion of TAVO412

Drug: TAVO412

Interventions

TAVO412 DRUG

Biologic

Part 1 Cohort1; Part 1 Cohort2; Part 1 Cohort3; Part 1 Cohort4; Part 1 Cohort5; Part 1 Cohort6; 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 18 years of age or older at the time of screening. 2. Voluntarily signed informed consent, understand the study and are willing to follow and have the ability to complete all trial procedures.
• \. Subjects with histologically or cytologically pathologically confirmed locally advanced unresectable or metastatic solid tumors that have failed standard therapy or have no standard therapy. There is no limit to the number of treatments that can be used in a previous regimen.
• \. ECOG performance status 0 or 1. 5. Expected survival ≥ 3 months. 6. Participants enrolled in Phase 2 must have at least one measurable (RECIST v1.1 criteria) lesion, and participants enrolled in Phase 1 may also be enrolled if only non-measurable (RECIST v1.1 criteria) lesions are present. Neoplastic lesions located in the field of prior radiation therapy or treated with other local therapies are not considered measurable unless disease progression has been demonstrated.
• \. Phase 1: Subjects with advanced or metastatic solid tumors who have failed standard therapy or have no standard treatment.
• \. Phase 2: A new cohort of subjects with advanced or metastatic solid tumors who have failed or had no standard therapy and are of high prevalence in China, such as non-small cell lung cancer, gastric cancer, and liver cancer, or other solid tumor types with the best clinical response observed from Phase 1 (e.g., CR \> PR \> SD).
• For subjects with non-small cell lung cancer: histologically or cytologically confirmed non-small cell lung cancer with mutations or gene amplification in EGFR, MET, or VEGF genes, EGFR or cMET overexpression (refer to IHC≥2+ in the Central Laboratory Immunohistochemistry Antibody Interpretation Criteria, ≥ intermediate staining).
• For subjects with gastric cancer: histopathologically confirmed gastric cancer or gastroesophageal junction cancer (including lower esophageal adenocarcinoma) with mutations or gene amplifications in EGFR, MET, or VEGF genes, EGFR or cMET overexpression (IHC≥2+ in reference central laboratory immunohistochemistry antibody interpretation criteria, ≥ moderate staining).
• For subjects with hepatocellular carcinoma: histologically or cytologically pathologically confirmed primary hepatocellular carcinoma with mutations or gene amplification in EGFR, MET or VEGF, overexpression of EGFR or cMET (IHC≥2+ in reference central laboratory immunohistochemistry antibody interpretation standards, ≥ moderate staining).
• Note: The tumor biopsy test report performed by the subject for other purposes (i.e., not a protocol-defined procedure) within 1 year prior to signing the consent form can be used as the basis for pre-treatment biopsy evaluation, and if metastases or recurrences of other tumors have occurred within 1 year, they are excluded.
• \. Stage 2: Willing to undergo pre-treatment and end-of-treatment (if appropriate) tumor biopsy (rough needle aspiration or excision) of a tumor tissue sample for biomarker immunohistochemistry and genetic testing.
• Note: Tumor biopsy archival tissue samples performed by subjects for other purposes (i.e., not protocol-defined procedures) within 1 year prior to signing the consent form may be used as pre-treatment tumor biopsy tissue samples, excluded if metastases or recurrences of other tumors have occurred within 1 year.
• Note: Subjects are required to provide 4-6 blank sections with a layer thickness of 3-5 μm and 10-12 blank sections with a layer thickness of 8-10 μm, or preferably 1 tissue block for EGFR and cMET immunohistochemistry and polygenic mutation/amplification detection. If the amount of tumor tissue obtained is limited, it is important to prioritize the need for EGFR and cMET immunohistochemistry detection (at least 4 blank sections with a layer thickness of 3-5 μm), followed by tumor tissue polygenic detection (10-12 blank sections with a layer thickness of 8-10 μm), and finally FISH detection for EGFR and MET gene amplification of tumor tissue (4-6 blank sections with a thickness of 3-5 μm).
• Note: Pre-treatment tumor tissue sections are not mandatory for subjects in Phase 2 if the tumor biopsy test report for other purposes (i.e., not a protocol-defined procedure) within 1 year prior to signing the consent form contains EGFR or cMET immunohistochemistry results. At the end of treatment, it is not suitable for/unwilling to provide tissue samples or other reasons that preclude tumor biopsy, and tumor biopsy is not mandatory.
• Note: Tumor tissue samples are optional before and at the end of treatment in Phase 1, and best efforts should be made to obtain tumor tissue if possible. Test results are collected if the subject has had a tumor biopsy for other purposes (i.e., not a protocol-defined procedure) within 1 year prior to signing the consent form, and the test results contain EGFR, cMET, or VEGF.
• \. For Phase 1 and Phase 2, subjects agree to collect additional peripheral blood for circulating tumor cell DNA (ctDNA) analysis.

You may not qualify if:

• \. Prior to the first dose of study drug, received an anticancer drug or investigational drug at the following time intervals:
• Chemotherapy, targeted small molecule therapy, or radiotherapy ≤ 14 days. Subject requires long-term corticosteroid use and develops radiation pneumonitis as a result of radiotherapy. A washout period of 1 week after palliative radiotherapy for non-central nervous system (CNS) disease is allowed with the approval of the sponsor. Note: The investigator can judge the washout period at the discretion of the subject according to the subject's condition and the nature of the drug; TKI drugs have a short half-life, and the washout period is more than 5 half-lives.
• Note: Bisphosphonates and denosumab are allowed concomitant medications. • ≤ immunotherapy or cell therapy prior to 28 days (i.e., chimeric antigen receptor T cell therapy; Other cell therapies must be discussed with the investigator to determine eligibility).
• ≤ Monoclonal antibodies used for anticancer therapy prior to 28 days, with the exception of denosumab.
• ≤ Chinese medicine used for anti-tumor before 14 days.
• ≤ 7 days for immunosuppressive therapy for any reason. Note: The use of inhaled or topical steroids or corticosteroids for imaging procedures is permitted.
• Note: Physiologic corticosteroid replacement therapy may be approved after consultation with the investigator (systemic prednisone or equivalent corticosteroid doses of ≤10mg/day are allowed).
• All other investigational drugs or devices are ≤ 28 days or 5 half-lives (whichever is longer) prior to the first dose. For investigational drugs with longer half-lives (e.g., \> 5 days), investigator approval is required for enrollment prior to the fifth half-life.
• \. Have not recovered from the toxic effects of prior therapy (including prior immunotherapy) and/or complications of surgical intervention to CTCAE v5.0 score ≤ Grade 1.
• Note: Subjects with stable chronic AEs (≤ Grade 2) that are not expected to resolve spontaneously (e.g., peripheral neuropathy and alopecia) are exceptions and may be enrolled after receiving investigator approval.
• Note: Subjects with a history of clinically symptomatic ocular disease judged by the investigator to be severe or uncontrollable will be excluded, including but not limited to severe or uncontrollable keratitis, dry eye syndrome, conjunctivitis, blurred vision, visual impairment, uveitis, etc.
• Note: Subjects with a history of prior therapy-related Grade 3 or higher AEs (excluding hematologic AEs) are excluded from the dose escalation portion of the study. The investigator can analyze the AE according to the time of occurrence and recovery.
• \. Other malignant tumors at the same time, such as tumors that occurred and cured 5 years ago, do not affect enrollment: melanoma, skin cancer, carcinoma in situ or non-invasive tumors.
• \. Previous clinically significant cardiac disease within 6 months prior to the first study drug administration, including:
• i. myocardial infarction, ii. Unstable angina, iii. Cerebrovascular accident, iv. Other acute uncontrollable cardiac disease;

Sponsors & Collaborators

• Tavotek Biotherapeutics: lead

Study Sites (6)

Affiliated Cancer Hospital of Chongqing University

Chongqing, Chongqing Municipality, China

NOT YET RECRUITING

First Affiliated Hospital of Xiamen University

Xiamen, Fujian, China

NOT YET RECRUITING

Zhujiang Hospital of Southern Medical University

Guangzhou, Guangdong, China

RECRUITING

Henan Cancer Hospital

Zhengzhou, Henan, 450003, China

RECRUITING

Hubei Cancer Hospital

Wuhan, Hubei, China

RECRUITING

Jinan Central Hospital

Jinan, Shandong, China

RECRUITING

MeSH Terms

Conditions

Neoplasms

Study Officials

• Suxia Luo, Dr.

  Henan Cancer Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yanjiao Yu, Bachelor

CONTACT

+86-13844867995; yanjiao.yu@tavotek.com

Wei Zhang, Master

CONTACT

+8618917679969; wei.zhang@tavotek.com

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: December 30, 2024
• First Posted: January 7, 2025
• Study Start: December 20, 2023
• Primary Completion: January 1, 2026
• Study Completion (Estimated): October 15, 2026
• Last Updated: January 16, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

CN (6)