ADI-270 for Renal Cell Carcinoma

Not currently recruiting at 1 trial location

Overseen By Adicet Medical Director

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Adicet Therapeutics

Must be taking: Immune checkpoint, VEGF inhibitors

Must not be taking: Corticosteroids, CD70 therapies

Disqualifiers: CNS metastases, Active malignancy, others

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called ADI-270 for individuals with renal cell carcinoma (RCC) that has recurred or spread after treatment. The goal is to determine the right dose and assess its effectiveness. Initially, the trial will test different doses and then expand to confirm the optimal one. Individuals diagnosed with clear cell RCC, who have tried treatments like immune and VEGF inhibitors, and whose cancer is advanced or has spread, might be suitable for this trial. As a Phase 1, Phase 2 trial, this research aims to understand how the treatment works in people and measure its effectiveness in an initial, smaller group, offering participants the chance to contribute to groundbreaking cancer treatment advancements.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, you need to be at least three weeks or 5 half-lives from your last dose of prior systemic therapy before starting the trial.

Is there any evidence suggesting that ADI-270 is likely to be safe for humans?

Research has shown that ADI-270 is an experimental treatment currently being tested for safety in individuals with kidney cancer. As this study is in its early stages (Phase 1/2), it aims to determine the appropriate dose and assess tolerability. Consequently, there is limited safety information from human testing at this stage.

The testing of ADI-270 in humans suggests that earlier lab studies indicated potential safety for human trials. The FDA has granted it a fast track designation, indicating promise in treating certain cancers. However, side effects and tolerability remain under close observation. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about ADI-270 for renal cell carcinoma because it offers a new approach compared to standard treatments like targeted therapies or immunotherapies. Unlike other treatments that primarily focus on inhibiting specific growth pathways or boosting the immune system broadly, ADI-270 is designed to precisely identify and attack cancer cells by leveraging a novel mechanism of action. This targeted approach aims to minimize damage to healthy cells, potentially leading to fewer side effects and improved patient outcomes.

What evidence suggests that ADI-270 might be an effective treatment for renal cell carcinoma?

Research has shown that ADI-270, the investigational treatment in this trial, may help treat certain cancers, such as clear cell renal cell carcinoma (ccRCC). Studies have found that ADI-270 can slow tumor growth in cancers with the CD70 protein, including ccRCC. This treatment uses a special immune cell, known as a gamma-delta T cell, to locate and attack cancer cells with the CD70 protein. Early results suggest that ADI-270 might be effective because it remains active in the body longer, enhancing its ability to fight cancer. By targeting various CD70-positive cancers, ADI-270 presents a promising new treatment option for patients with this condition. ^{2 3 4 6 7}

Are You a Good Fit for This Trial?

This trial is for patients with advanced or metastatic clear cell Renal Cell Carcinoma (ccRCC) who have previously been treated with an immune checkpoint inhibitor and a VEGF inhibitor. Participants must be in good physical condition, as indicated by a Karnofsky Performance Status (KPS) of 70 or above, and should not have received their last systemic therapy within three weeks or less than five half-lives of the drug.

Inclusion Criteria

My kidney cancer is confirmed to be clear cell type.

My cancer has spread beyond its original location.

I have been treated with both an immune checkpoint inhibitor and a VEGF inhibitor for advanced cancer.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

ADI-270 is administered at ascending dose levels as a single dose to determine the maximum tolerated dose (MTD) or maximum assessed dose (MAD) of ADI-270

4 weeks

Dose Expansion

Dose Expansion with ADI-270 at the MTD/MAD to confirm recommended phase 2 dose

Variable

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

What Are the Treatments Tested in This Trial?

Interventions

• ADI-270

Trial Overview The study is testing ADI-270, an engineered T-cell therapy targeting CD70, along with Fludarabine and Cyclophosphamide in patients whose ccRCC has returned after treatment. It's a two-part study that first finds the best dose of ADI-270 and then tests its effectiveness at that dose.

How Is the Trial Designed?

Group I: Dose Expansion Experimental Treatment 3 Interventions

Dose Expansion with ADI-270 at the MTD/MAD to confirm recommended phase 2 dose (Part 2).

Group II: Dose Escalation Experimental Treatment 3 Interventions

ADI-270 is administered at ascending dose levels as a single dose to determine the maximum tolerated dose (MTD) or maximum assessed dose (MAD) of ADI-270

ADI-270 is already approved in United States for the following indications:

Approved in United States as ADI-270 for:

• None - Currently in Phase 1/2 clinical trials for metastatic/advanced clear cell renal cell carcinoma (ccRCC)

Who Is Running the Clinical Trial?

Adicet Therapeutics

Lead Sponsor

Trials

4

Recruited

370+

Published Research Related to This Trial

Since 2005, six new therapies have been approved for treating renal cell carcinoma, significantly changing treatment options and targeting pathways involved in tumor growth and spread.

Understanding the pharmacology of these therapies is crucial for clinicians to educate patients, ensure adherence to treatment, and identify side effects early, ultimately leading to better clinical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New therapeutic strategies for renal cell carcinoma. Wood, LS.[2022]

Immunotherapy has been the leading treatment for advanced renal cell carcinoma, but its clinical effectiveness has been largely disappointing, prompting the search for better options.

New agents targeting specific biological abnormalities of renal cell carcinoma are currently being tested in clinical trials, showing promising early results that could improve treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Will the dark sky over advanced renal cell carcinoma soon become brighter? D'Hondt, V., Gil, T., Lalami, Y., et al.[2007]

AMG 172, an anti-CD27L antibody-drug conjugate, was found to have a maximum tolerated dose of 1.6 mg/kg, with common side effects including thrombocytopenia and liver injury, leading to treatment discontinuation in some cases.

While AMG 172 demonstrated a favorable pharmacokinetic profile, only 5.4% of patients experienced a partial response, indicating limited antitumor activity in patients with relapsed/refractory clear cell renal cell carcinoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-in-human study to assess safety, tolerability, pharmacokinetics, and pharmacodynamics of the anti-CD27L antibody-drug conjugate AMG 172 in patients with relapsed/refractory renal cell carcinoma. Massard, C., Soria, JC., Krauss, J., et al.[2020]

In a study of 53 patients with metastatic renal cell carcinoma (RCC) who had previously progressed after other treatments, carboxyamidotriazole (CAI) showed limited efficacy, with only 1.9% achieving a partial response and 11.3% remaining disease-free at 6 months.

While most side effects were mild (Grade 1), some patients experienced severe gastrointestinal toxicities, indicating that while CAI is generally safe, it can still cause significant adverse effects in a small number of cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of carboxyamidotriazole in patients with advanced renal cell carcinoma refractory to immunotherapy: E4896, an Eastern Cooperative Oncology Group Study. Dutcher, JP., Leon, L., Manola, J., et al.[2017]

Recent advances in understanding renal cell cancer (RCC) have led to the development of six new targeted therapies that significantly improve progression-free survival (PFS) compared to previous treatments, with a consistent doubling of PFS observed in clinical trials.

These new drugs, including sorafenib and sunitinib, are generally well tolerated and provide clinical benefits to over 70% of patients, although their unique side effects require careful management to maintain quality of life during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeted therapy in renal cancer. Dorff, TB., Goldkorn, A., Quinn, DI.[2021]

Citations

1. investor.adicetbio.com investor.adicetbio.com/news-releases/news-release-details/adicet-bio-announces-first-patient-dosed-phase-1-clinical-trial

Adicet Bio Announces First Patient Dosed in the Phase 1 ... ADI-270 is also designed to increase exposure and persistence by reducing susceptibility to host vs. graft elimination. These properties of ADI- ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06480565

NCT06480565 | A Phase 1/2 Trial of ADI-270 in ccRCC This is a Phase 1/2 multicenter, open-label, dose escalation, and dose expansion study of ADI-270 - an Engineered gamma-delta Chimeric Receptor [CAR] Vδ1 T ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12215124/

ADI-270: an armored allogeneic gamma delta T cell ... ADI-270 has the potential to target multiple CD70+ cancers with initial clinical evaluation proceeding in relapsed/refractory clear cell renal ...

4. targetedonc.com targetedonc.com/view/adi-270-gains-fda-fast-track-status-in-metastatic-advanced-ccrcc

ADI-270 Gains FDA Fast Track Status in Metastatic ... A fast track designation has been given to ADI-270 from the FDA for treating metastatic or advanced clear cell renal cell carcinoma (ccRCC) ...

5. urologytimes.com urologytimes.com/view/first-patient-dosed-in-phase-1-trial-of-adi-270-in-ccrcc

First patient dosed in phase 1 trial of ADI-270 in ccRCC Data showed that ADI-270 significantly inhibited tumor growth in CD70-positive clear cell RCC models, as well as other solid malignancies. The ...

6. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.TPS4613

A phase 1/2 first in human study of ADI-270, an armored ... Despite advancements in the treatment of patients with metastatic RCC, the 5-year survival rate is 15% and there remains an unmet need. ADI-270 ...

7. cancernetwork.com cancernetwork.com/view/fda-grants-fast-track-designation-to-adi-270-in-advanced-clear-cell-rcc

FDA Grants Fast Track Designation to ADI-270 in ... Developers designed ADI-270 to potentially improve clinical responses in patients with renal cell carcinoma and other CD70-positive tumors.