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

Phase 1

Recruiting

• 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
• Interventions: Drug: TT-10; Drug: TT-4

• Registration Number: NCT04969315
• Lead Sponsor: Portage Biotech

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. To evaluate the safety and tolerability of TT-10, TT-4 and TT-10 + TT-4, (Dual Blockade)

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. To obtain a preliminary estimate of efficacy of TT-10, TT-4 and TT-10 + TT-4, (Dual Blockade) in advanced solid tumors.

Detailed Description

Multicenter, open-label dose-escalation Phase I/II clinical study, designed to evaluate the safety, tolerability, PK, PD, anti-tumor activity, and efficacy of TT-10, TT-4 and TT-10 + TT-4 (Dual Blockade).

The Phase Ia portion of the study study will consist of three dose escalation cohorts, to determine the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D), safety and tolerability of TT-10, TT-4, TT-10 + TT-4 and will be conducted in participants with the following advanced cancers:

Cohort A (TT-10): Renal cell cancer (RCC), castrate resistant prostate cancer (CRPC), non-small cell lung cancer (NSCLC), squamous cell carcinoma of the head and neck (SCCHN); who have failed or are not eligible for standard of care treatment.

Cohort B (TT-4): Castrate resistant prostate cancer (CRPC), non-small cell lung cancer (NSCLC), colorectal cancer (CRC), endometrial cancer (EC) and ovarian cancer (OC); who have failed or are not eligible for standard of care treatment.

Cohort C (TT-10 + TT-4): Tumor types from both cohorts will be included and prioritized based on the data observed.

Study Timeline

• Study First Submitted: 2021-07-05
• Study First Submitted QC: 2021-07-09
• Study First Posted: 2021-07-20
• Study Start: 2023-06-23
• Status Verified: 2025-03
• Last Update Submitted: 2025-03-28
• Last Update Posted: 2025-04-02
• Primary Completion: 2026-06-01
• Study Completion: 2027-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 90

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Cohort A: Dose Escalation	TT-10	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
Cohort B: Dose Escalation	TT-4	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
Cohort C: Dose Escalation	TT-10	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
Cohort C: Dose Escalation	TT-4	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

Primary Outcome Measures

Name	Time	Method
Number of subjects with Dose Limiting Toxicities (DLTs) of TT-10, TT-4 and TT-10 + TT-4 during the dose escalation phase	28 Days	All toxicities will be graded using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.0
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	Through study completion, an average of 1 year	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
Expansion cohort primary objective - safety	Through study completion, an average of 1 year	Incidence and severity of treatment-related adverse events (TRAEs) in participants treated at the recommended phase 2 dose in the expansion phase

Secondary Outcome Measures

Name	Time	Method
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)	ORR is to be reported as the proportion of patients who have a Complete Response or Partial Response per Response Evaluation Criteria In Solid Tumors (RECIST) 1.1
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)	Defined as the time from first documented objective response per Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 to the date of first documented radiographic progression of disease (PD) or death.
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)	Time from first dose to the date of the first confirmed documented progression per Response Evaluation Criteria In Solid Tumors (RECIST) 1.1
Peak serum concentration (Cmax) of TT-10	Predose, 0.5, 1, 2, 4, 6, 8, 24 hours post-dose	PK Parameter
Area under the serum concentration versus time curve (AUC) of TT-10	Predose, 0.5, 1, 2, 4, 6, 8, 24 hours post-dose	PK Parameter
Half-life of TT-10	Predose, 0.5, 1, 2, 4, 6, 8, 24 hours post-dose	PK Parameter

Trial Locations

Locations (3)

USC Norris Comprehensive Cancer Center; 🇺🇸 Los Angeles, California, United States

Norton Cancer Institute; 🇺🇸 Louisville, Kentucky, United States

The University of Texas MD Anderson Cancer Center; 🇺🇸 Houston, Texas, United States