TT-10 (PORT-6) and TT-4 (PORT-7) as Single Agents and in Combination in Subjects With Advanced Selected Solid Tumors

NCT04969315 | Recruiting Phase 1 FDA Drug

• 3 other identifiers: TT-10-101/ADPORT-601TT-10-101TT-4-101
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 3

Brief Summary

The goal of this clinical trial is to evaluate TT-10, TT-4 and TT-10 + TT-4, (Dual Blockade) in participants with advanced selected solid tumors, who have failed or are not eligible for standard of care. The main questions it aims to answer are:

1. 1.To evaluate the safety and tolerability of TT-10, TT-4 and TT-10 + TT-4, (Dual Blockade)
2. 2.To determine the maximum tolerated dose or the recommended phase 2 dose of TT-10, TT-4 and TT-10 + TT-4, (Dual Blockade)
3. 3.To obtain a preliminary estimate of efficacy of TT-10, TT-4 and TT-10 + TT-4, (Dual Blockade) in advanced solid tumors.

Conditions

Renal Cell Cancer; Castrate Resistant Prostate Cancer; Non Small Cell Lung Cancer; Head and Neck Squamous Cell Carcinoma; Colorectal Cancer (CRC); Endometrial Cancer; Ovarian Cancer

Keywords

Failed or not eligible for standard of care; Advanced Selected Solid Tumors; TT-10; Adenosine; Adenosine Antagonist; A2A; A2AR Inhibitor; PORT-6; ADPORT-601; TT-4; PORT-7; A2B; Dual; A2AR; A2BR

Outcome Measures

Primary Outcomes (3)

• Number of subjects with Dose Limiting Toxicities (DLTs) of TT-10, TT-4 and TT-10 + TT-4 during the dose escalation phase

  All toxicities will be graded using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.0

  28 Days

• Define the maximum tolerated dose (MTD) or phase 2 recommended dose of TT-10, TT-4 and TT-10 + TT-4 during the dose escalation phase

  To confirm the maximum tolerated dose (MTD) of TT-10, TT-4 and TT-10 + TT-4, defined as the highest dose level at which \<2 out of 6 participants experience a dose-limiting toxicity

  Through study completion, an average of 1 year

• Expansion cohort primary objective - safety

  Incidence and severity of treatment-related adverse events (TRAEs) in participants treated at the recommended phase 2 dose in the expansion phase

  Through study completion, an average of 1 year

Secondary Outcomes (6)

• Overall Response Rate (ORR)

  From study enrollment until participant discontinuation, first occurrence of progressive disease, or death from any cause, whichever occurs first (approximately 2 years)

• Duration of Response (DoR)

  From study enrollment until participant discontinuation, first occurrence of progressive disease, or death from any cause, whichever occurs first (approximately 2 years)

• Progression Free Survival (PFS)

  From study enrollment until participant discontinuation, first occurrence of progressive disease, or death from any cause, whichever occurs first (approximately 2 years)

• Peak serum concentration (Cmax) of TT-10

  Predose, 0.5, 1, 2, 4, 6, 8, 24 hours post-dose

• Area under the serum concentration versus time curve (AUC) of TT-10

  Predose, 0.5, 1, 2, 4, 6, 8, 24 hours post-dose

Study Arms (3)

Cohort A: Dose Escalation

EXPERIMENTAL

Drug: TT-10 (A2A Receptor Antagonist) * Supplied in capsules for daily oral administration twice a day (BID) * One cycle is considered 28 days * Ascending Dose levels are being explored * Dose Level 1 * Dose Level 2 * Dose Level 3 * Dose Level 4\* \*Additional dose levels may be explored, if appropriate based on emerging safety, PK or pharmacodynamic data

Drug: TT-10

Cohort B: Dose Escalation

EXPERIMENTAL

Drug: TT-4 (A2B Receptor Antagonist) * Supplied in capsules for daily oral administration once a day (QD) * One cycle is considered 28 days * Ascending Dose levels are being explored * Dose Level 1 * Dose Level 2 * Dose Level 3\* * \*Additional dose levels or frequency may be explored, if appropriate based on emerging safety, PK or pharmacodynamic data

Drug: TT-4

Cohort C: Dose Escalation

EXPERIMENTAL

Drugs: TT-10 + TT-4 - Dual Receptor Antagonists * Both drugs will be supplied in capsules for daily oral administration and administered separately. * One cycle is considered 28 days * Ascending Dose levels of both drugs are being explored and will be determined after safety review of Cohorts A and B

Drug: TT-10; Drug: TT-4

Interventions

TT-10 DRUG

TT-10 orally administered BID

Cohort A: Dose Escalation; Cohort C: Dose Escalation

TT-4 DRUG

TT-4 is orally administered QD

Cohort B: Dose Escalation; Cohort C: Dose Escalation

Eligibility Criteria

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

You may not qualify if:

• Administration of a live vaccine within 6 weeks of first dose of study intervention. Messenger ribonucleic acid (mRNA) vaccines for the prevention of Coronavirus Disease 2019 (COVID-19) infection are permitted.
• Baseline QT interval corrected with Fridericia's method (QTcF) \> 470 ms (average of triplicate readings)
• a. NOTE: Criterion does not apply to participants with a right or left bundle branch block.
• Prior surgery or gastrointestinal dysfunction that may affect drug absorption (eg, gastric bypass surgery, gastrectomy)
• Female participants who are pregnant or breastfeeding
• Concurrent active malignancy other than non-melanoma skin cancer, carcinoma in situ of the cervix or prostate intraepithelial neoplasia
• Past medical history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis which required steroid treatment, or any evidence of clinically active interstitial lung disease
• History of peptic ulcer and/or gastrointestinal bleed within the past 6 months prior to Screening
• History of stroke, unstable angina, myocardial infarction or ventricular arrhythmia requiring medication or mechanical control within the last 6 months prior to Screening
• Unstable or severe uncontrolled medical condition (eg, unstable cardiac function, unstable pulmonary condition including pneumonitis and/or interstitial lung disease, uncontrolled diabetes) or any important medical illness or abnormal laboratory finding that would, in the investigator's judgment, increase the risk to the participant associated with his or her participation in the study

Sponsors & Collaborators

• Portage Biotech: lead

Study Sites (3)

USC Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

RECRUITING

Norton Cancer Institute

Louisville, Kentucky, 40241, United States

RECRUITING

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Related Publications (12)

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MeSH Terms

Conditions

Carcinoma, Renal Cell; Carcinoma, Non-Small-Cell Lung; Squamous Cell Carcinoma of Head and Neck; Colorectal Neoplasms; Endometrial Neoplasms; Ovarian Neoplasms

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Squamous Cell; Head and Neck Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Uterine Neoplasms; Genital Neoplasms, Female; Uterine Diseases; Genital Diseases, Female; Genital Diseases; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Endocrine System Diseases; Gonadal Disorders

Central Study Contacts

Desa Rae E Stanton-Pastore, MS

CONTACT

1585-305-3850; desi@portagebiotech.com; drpastore@cyncado.com

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: July 5, 2021
• First Posted: July 20, 2021
• Study Start: June 23, 2023
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): December 31, 2027
• Last Updated: April 2, 2025

Record last verified: 2025-03

Locations

US (3)