ADI-270 for Renal Cell Carcinoma

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

60 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug ADI-270 for renal cell carcinoma?

While there is no direct data on ADI-270, other drugs targeting similar pathways in renal cell carcinoma have shown positive results, doubling the time patients live without the disease getting worse and improving overall survival. These drugs work by interfering with blood vessel growth that tumors need to grow, suggesting a potential benefit for ADI-270 if it acts similarly. ^{1 2 3 4 5}

What is the purpose of this trial?

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 Cell product Targeting CD70 - in patients with R/R ccRCC.

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Targeted therapy in renal cancer. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

New therapeutic strategies for renal cell carcinoma. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Will the dark sky over advanced renal cell carcinoma soon become brighter? [2007]

4. Germany 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. [2020]

5. United States 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. [2017]