An investigation of selective targeting of A2AR in patients with certain solid tumors is underway in a first-in-human study.
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PORT-6 (TT-10), an adenosine 2A receptor (A2AR) antagonist, has been dosed in the first patient, initiating treatment in the phase 1a ADPORT-601 trial (NCT04969315) of patients with solid tumors, including prostate cancer, renal cell carcinoma (RCC) and non–small cell lung cancer (NSCLC).1
Modest activity has been shown with inhibition of the adenosine pathway in other studies of patients with RCC, prostate cancer, NSCLC, and other tumors models, like melanoma, gastroesophageal cancer, and colorectal cancer. It has also been suggested through preclinical research that by binding adenosine, antitumor immune responses can be induced in solid tumors. According to Sumit K. Subudhi, MD, PhD, this is because high adenosine signaling is associated with worse survival rates.1,2
“When you think of it in terms of immune checkpoint therapy…the patients with higher adenosine signaling levels are more likely to progress on immune checkpoint therapy whereas patients who have lower adenosine signaling levels are more likely to respond to these immune checkpoint therapies,” said Subudhi, associate professor, Department of Genitourinary Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, during a conference call hosted by Portage Biotech.2
Trial Name: Phase I/II First-in-Human Study of TT-10 as a Single Agent in Subjects With Advanced Selected Solid Tumors
ClinicalTrials.gov Identifier: NCT04969315
Sponsor: Tarus Therapeutics, Inc.
Recruitment Contact:
+1-860-539-2649, clinicaltrials@portagebiotech.com
Completion Date: August 14, 2025
ADPORT-601 is a multicenter, first-in-human study with a goal of evaluating safety, tolerability, pharmacokinetics, pharmacodynamics, antitumor activity, and other efficacy outcomes in patients with advanced solid tumors. Up to 90 patients will be included in the study.4
In 2 phases, the study will first determine the recommended phase 2 dose, maximum-tolerated dose, and safety/tolerability of PORT-6 based on the number of patients with dose-limiting toxicities and the incidence and severity of treatment-related adverse events (TRAEs). The secondary end points of the study will be overall response rate, duration of response, progression-free survival, peak serum concentration, area under the serum concentration curve vs the time curve, and the half-life of PORT-6.
“The PORT-6 A2AR antagonist and PORT-7 A2BR [adenosine 2B receptor] antagonist trial should provide insight into understanding the therapeutic implications of targeting each pathway alone or in combination together at optimum biologic doses in multiple cancer types, something we have not been able to do before in this field. We look forward to evaluating the potential of Portage’s adenosine antagonists in this clinical trial, which should also provide insights into potentially improving on current patient selection strategies by selecting patients whose tumors have a high level of adenosine expression,” said Lawrence Fong, MD, Hellen Diller Family Comprehensive Cancer Center at the University of California, San Francisco, in a press release.1
Patients are eligible to participate in the ADPORT-601 trial if they are 18 years of age or older, have a histologically of cytologically confirmed advanced solid tumor, an ECOG performance status of 0 or 1, measurable disease per RECIST v1.1, did not respond to standard therapy, have a life expectancy of at least 3 months, and have adequate hematologic, hepatic, and renal function.4
Individuals may not enroll if they have undergone major surgery within 4 weeks before screening, radiotherapy within 2 weeks of the start of study treatment, a live vaccine within 6 weeks of the first dose of study treatment, or prior anti-cancer therapy within 4 weeks of study treatment. Patients who need immunosuppressive therapy, strong inhibitors, or inducers like CYP3A4, 2C9, or 2C19, or drugs to alter gastric pH are not eligible for the study. Moreover, those with history of or active infections or illnesses of a certain nature may be excluded from the study.
Sarah Cannon Research Institute in Denver, Colorado is the first site to recruit patients for the ADPORT-601 trial. Once full recruitment begins, patients will be given the investigational treatment at sites in California, Kentucky, Missouri, Pennsylvania, Texas, and Virginia.4
“We are excited to announce the first patient dosed in the phase 1a safety portion of the ADPORT-601 trial in collaboration with our academic partners. This trial is a critical next step in our comprehensive exploration of how targeting the adenosine pathway could improve outcomes in multiple cancer types,” said Ian Walters, MD, chief executive officer and chairman of Portage Biotech, in the press release.1 “Adenosine pathway blockade has shown safety and monotherapy activity in numerous solid tumors, and PORT-6 represents a next-generation approach which we believe is, based on our pre-clinical studies, more potent, durable, and selective than other agents. We are continuing to advance this program along with the ongoing development of our iNKT engager, PORT-2, giving us multiple potential product candidates for patients in need.”
REFERENCES
1. Portage Biotech announces first patient dosed in phase 1a trial of port-6 in select solid tumors, News release. Portage Biotech Inc. June 26, 2023. Accessed June 29, 2023. https://tinyurl.com/vvp7fmej
2. Portage Biotech KOL event: Targeting adenosine for cancer. March 9, 2023. Accessed June 29, 2023. https://tinyurl.com/ysrpzmzs
3. Sidders B, Zhang P, Goodwin K, et al. Adenosine signaling is prognostic for cancer outcome and has predictive utility for immunotherapeutic response. Clin Cancer Res. 2020; 26 (9): 2176–2187. doi:10.1158/1078-0432.CCR-19-2183
4. TT-10 as a single agent in subjects with advanced selected solid tumors. ClinicalTrials.gov. Updated May 12, 2023 Accessed June 29, 2023. https://classic.clinicaltrials.gov/ct2/show/NCT04969315
