TT-10 for Advanced Cancer

(ADPORT-601 Trial)

Recruiting at 8 trial locations

Overseen By Desa Rae E Stanton-Pastore, MS

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Portage Biotech

Must not be taking: Immunosuppressants, CYP3A4 inhibitors

Disqualifiers: Active CNS metastases, HIV, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

90 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests new treatments for individuals with advanced solid tumors who haven't responded to standard treatments. It will evaluate the safety and effectiveness of two drugs, TT-10 (a new potential drug) and TT-4, either alone or in combination. Eligible participants have specific types of advanced cancer, such as certain lung or prostate cancers, and have not found success with other treatments. As a Phase 1 trial, this research aims to understand how the treatment works in people, providing participants the opportunity to be among the first to receive a new potential drug.

Do I need to stop my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot participate if you require certain drugs like strong inhibitors or inducers of specific enzymes, or drugs that modify stomach acid levels. It's best to discuss your current medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that treatments like TT-10 and TT-4, which block certain cell receptors, may help control cancer and enhance other cancer therapies. Previous studies on TT-10 have examined its safety and effectiveness, often in combination with other therapies. These studies have not identified major safety issues, indicating it is generally safe to use.

TT-4 targets a specific receptor and has been studied for its potential to aid the immune system in fighting cancer. Although limited safety data exists on TT-4 alone, it functions similarly to TT-10, which has been tested in humans without serious side effects.

Research on using TT-10 and TT-4 together suggests that targeting both receptors might strengthen the immune response against tumors, combining the benefits of both treatments. However, detailed safety information on their combined use is still being gathered.

As this trial is in its early stages, the main goal is to ensure these treatments are safe and to determine the optimal dose. While early results are promising, more data is needed to confirm how well these treatments are tolerated. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about TT-10 and TT-4 because they offer a novel approach to treating advanced cancer by targeting specific receptors in the body. Unlike conventional treatments that often focus on chemotherapy and radiation, TT-10 acts as an A2A receptor antagonist, potentially altering the tumor environment to improve immune response. Meanwhile, TT-4 targets the A2B receptor, which may also play a role in cancer progression. This dual-target strategy could provide a more tailored and potentially effective treatment option, especially for patients who have not responded well to existing therapies.

What evidence suggests that this trial's treatments could be effective for advanced cancer?

Research shows that TT-10, a medicine that blocks certain cell signals, has potential in treating advanced solid tumors. In this trial, participants in Cohort A will receive TT-10 alone to explore its effects. Researchers are studying TT-4, another medicine that blocks different cell signals, separately in Cohort B for cancer treatment, although less information exists about its effectiveness. Cohort C will test the combination of TT-10 and TT-4, called Dual Blockade, to determine if it can better control tumors and improve survival in advanced cancers. Early results suggest that using both medicines together might enhance treatment effectiveness by targeting multiple pathways of cancer growth. ^{6 7 8 9 10}

Are You a Good Fit for This Trial?

Adults with advanced solid tumors like oral, head and neck, kidney, prostate or lung cancer who've not responded to standard treatments can join. They must have a life expectancy over 3 months, good blood and organ function, and be able to consent. Some need accessible tumors for biopsies.

Inclusion Criteria

My liver is functioning well.

My kidney function is within normal ranges.

I have RCC, CRPC, or NSCLC, can't get standard treatment, and my tumor can be biopsied.

Exclusion Criteria

I have not had radiotherapy in the last 2 weeks.

I have not had any cancer treatment in the last 4 weeks.

I have a history of hepatitis C.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive ascending doses of TT-10, TT-4, or TT-10 + TT-4 to determine the maximum tolerated dose

28 days per cycle

Weekly visits for dose escalation monitoring

Expansion Phase

Participants are treated at the recommended phase 2 dose to further evaluate safety and efficacy

1 year

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

What Are the Treatments Tested in This Trial?

Interventions

• TT-10

Trial Overview The trial is testing TT-10's safety when taken orally by patients with certain advanced cancers. It aims to find the highest dose patients can tolerate without severe side effects (MTD) or the suggested dose for future Phase 2 trials (RP2D).

How Is the Trial Designed?

Group I: Cohort C: Dose Escalation Experimental Treatment 2 Interventions

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

Group II: Cohort B: Dose Escalation Experimental Treatment 1 Intervention

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

Group III: Cohort A: Dose Escalation Experimental Treatment 1 Intervention

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

Who Is Running the Clinical Trial?

Portage Biotech

Lead Sponsor

Trials

1

Recruited

90+

Tarus Therapeutics, Inc.

Industry Sponsor

Trials

2

Recruited

90+

Published Research Related to This Trial

A new online toxicity registration strategy was developed for children and young adults treated under the Nordic/Baltic acute lymphoblastic leukaemia protocol, which streamlined the process and achieved a high compliance rate of 98.9% within 5 weeks.

This approach focuses on monitoring serious but rare adverse events, allowing for real-time toxicity profiles and early warnings for specific toxicities, which can enhance patient safety and inform treatment adjustments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Complying with the European Clinical Trials directive while surviving the administrative pressure - an alternative approach to toxicity registration in a cancer trial. Frandsen, TL., Heyman, M., Abrahamsson, J., et al.[2019]

In a phase III study involving 358 patients with advanced head and neck cancer, adding docetaxel to cisplatin and 5-fluorouracil (TPF) improved overall survival and reduced toxicity compared to the PF regimen.

Patients receiving TPF showed a trend towards better health-related quality of life (HRQOL) and experienced greater improvements in swallowing and coughing issues during treatment, suggesting that TPF may enhance patient well-being alongside survival benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Short-term health-related quality of life and symptom control with docetaxel, cisplatin, 5-fluorouracil and cisplatin (TPF), 5-fluorouracil (PF) for induction in unresectable locoregionally advanced head and neck cancer patients (EORTC 24971/TAX 323). van Herpen, CM., Mauer, ME., Mesia, R., et al.[2022]

A review of 81 clinical trials involving over 45,000 patients revealed that the reporting of adverse events (AEs) for targeted therapies and immunotherapies is often inadequate, particularly regarding recurrent/late toxicities and the duration of AEs.

The study highlights that more than 90% of trials failed to adequately report the timing and occurrence of all-grade AEs, indicating a need for improved transparency and detail in AE reporting in future oncology trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systematic Review of adverse events reporting in clinical trials leading to approval of targeted therapy and immunotherapy. Bossi, P., Botta, L., Bironzo, P., et al.[2020]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.e18154

Impact of targeted therapies (TT) and immunotherapy (IO) ... This study aim is to describe treatment outcomes in a nationwide cohort of ATC patients (pts) in the era of novel systemic therapies.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10930974/

Real-World Data on Clinical Outcomes and Treatment ... First-line treatment in the unresectable setting showed 5-year overall survival rates of 46.5% for anti-PD1, 52.4% for anti-CTLA4/PD1, and 49.2% ...

3. annalsofoncology.org annalsofoncology.org/article/S0923-7534(24)03347-7/fulltext

1736P An open label phase IIa study evaluating the ... Intratumoural TT appears safe for patients with STS. Efficacy in ablating injected tumours was observed across different histologic types. The primary endpoint ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04742959

NCT04742959 | Study of TT-00420 (Tinengotinib) Tablet ... This is a Phase Ib/II, multicenter, open-label study to evaluate the safety and preliminary efficacy of TT-00420 tablet, as monotherapy or in combination ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11883162/

Recent advances in Tumor Treating Fields (TTFields) therapy ... For the latter, results from a 30-patient study showed a median PFS of 9.3 months, median OS of 15.8 months, and 1-year survival of 66% (NCT03477110). Efficacy ...

6. pubs.acs.org pubs.acs.org/doi/10.1021/acsptsci.5c00057

Insights from Clinical Trials on A2A Adenosine Receptor ... While initial clinical trials demonstrated modest anticancer effects of monotherapy with A2A receptor antagonists, combination approaches, particularly with ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11434806/

Targeting the Adenosine A2A Receptor as a Novel ... An increasing number of studies suggest that the activation of A2AR can downregulate anti-tumor immune responses and prevent tumor growth.

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8616521/

Adenosine Receptor Antagonists to Combat Cancer and ... This review focuses on the potential of A 2A and A 2B receptor antagonists in cancer control and in boosting anti-cancer chemotherapy and immunotherapy.

9. clinicaltrials.gov clinicaltrials.gov/study/NCT02655822

NCT02655822 | Phase 1/1b Study to Evaluate the Safety ... This trial will study the safety, tolerability, and anti-tumor activity of ciforadenant as a single agent and in combination with atezolizumab, an intravenous ...

10. withpower.com withpower.com/trial/phase-2-carcinoma-renal-cell-8-2021-ef9bf

TT-10 for Advanced Cancer (ADPORT-601 Trial) This trial tests a new oral drug, TT-10, for safety and effectiveness in people with severe cancers that did not improve with usual treatments.