TORL-2-307-ADC for Advanced Cancer

Recruiting at11 trial locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: TORL Biotherapeutics, LLC

Must not be taking: Chemotherapy, Biologics

Disqualifiers: Brain metastases, Cardiac disease, MDS, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

This trial will test a new drug called TORL-2-307-ADC in patients with advanced cancer to see if it is safe and can help fight their cancer.

Will I have to stop taking my current medications?

The trial requires that you have not received any cancer treatments within 14 days for small molecule drugs and 28 days for biologic drugs before starting the study. It does not specify about other medications, so you should discuss your current medications with the trial team.

What makes the drug TORL-2-307-ADC unique for treating advanced cancer?

TORL-2-307-ADC is unique because it targets the CLDN18.2 protein, which is found in certain cancers like gastric and pancreatic cancers but not in most normal tissues. This allows the drug to deliver its cancer-fighting agent directly to the tumor cells, potentially reducing harm to healthy cells. ^{1 2 3 4 5}

Research Team

Ibrahim Qazi, PharmD

Principal Investigator

TORL Biotherapeutics, LLC

Eligibility Criteria

This trial is for adults with advanced solid tumors, including specific cancers of the stomach and pancreas. Participants must have measurable disease, be relatively fit (ECOG status 0-1), and have good organ function. They can't join if they've had recent cancer treatments, unresolved side effects from past therapies (except hair loss or certain lab abnormalities), brain metastases, serious heart conditions, other active cancers within the last 3 years (with some exceptions), or are pregnant/breastfeeding.

Inclusion Criteria

My organs are working well.

My cancer is advanced and can be measured by scans.

I am fully active or can carry out light work.

Exclusion Criteria

I still experience side effects from previous treatments, except for hair loss.

I do not have any serious illnesses or infections that are not under control.

I have a history of serious heart problems.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose-Escalation Treatment

Participants receive TORL-2-307-ADC to determine the maximum tolerated dose

28 days

Expansion Treatment

Participants receive TORL-2-307-ADC at the recommended phase 2 dose

up to 2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

up to 2 years

Treatment Details

Interventions

• TORL-2-307-ADC (Antibody-drug conjugate)

Trial Overview The study is testing TORL-2-307-ADC's safety and effectiveness against advanced cancers. It's a first-in-human trial meaning it's the first time this drug is being tested in people to see how well it works and how safe it is.

Participant Groups

Group I: Monotherapy Dose Dose Finding - Part 1 Experimental Treatment 1 Intervention

TORL-2-307-ADC

Group II: Expansion as Monotherapy - Part 2 Experimental Treatment 1 Intervention

TORL-2-307-ADC

Who Is Running the Clinical Trial?

TORL Biotherapeutics, LLC

Lead Sponsor

Trials

6

Recruited

600+

Translational Research in Oncology

Collaborator

Trials

22

Recruited

6,700+

Findings from Research

Mirvetuximab Soravtansine (IMGN853) is an antibody drug conjugate that targets the folate receptor alpha and has shown promising effectiveness and a favorable safety profile in treating platinum-resistant ovarian cancer, particularly in patients with moderate-to-high FRα expression.

The ongoing phase III study comparing IMGN853 to standard chemotherapy aims to further establish its efficacy, while additional ADCs targeting other cancer markers are also being explored in early clinical trials, highlighting a growing strategy to enhance treatment for ovarian cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antibody-drug conjugates for ovarian cancer: current clinical development. Stewart, D., Cristea, M.[2019]

A novel therapeutic antibody (CLDN18.2-307-mAb) and an antibody-drug conjugate (CLDN18.2-307-ADC) targeting the CLDN18.2 protein have shown promising preclinical results in treating gastric and pancreatic cancers, which express this protein and are often resistant to current therapies.

The CLDN18.2-307-ADC demonstrated the ability to induce complete and sustained tumor regressions in xenograft models, indicating its potential efficacy, and both therapies are currently being tested in phase I clinical studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development of a Novel CLDN18.2-directed Monoclonal Antibody and Antibody-Drug Conjugate for Treatment of CLDN18.2-Positive Cancers. O'Brien, NA., McDermott, MSJ., Zhang, J., et al.[2023]

Brentuximab vedotin, an antibody-drug conjugate used for treating certain lymphomas, showed improved progression-free survival in patients with cutaneous T-cell lymphoma (CTCL) without a direct correlation to the drug's exposure levels, indicating its efficacy is consistent across different exposure ranges.

The study found that while higher exposure to the drug was linked to an increase in severe treatment-emergent adverse events (TEAEs), the results support the use of a standard dose of 1.8 mg/kg every 3 weeks, with the option for dose reductions in patients experiencing significant side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Population PK and Exposure-Response Relationships for the Antibody-Drug Conjugate Brentuximab Vedotin in CTCL Patients in the Phase III ALCANZA Study. Suri, A., Mould, DR., Liu, Y., et al.[2019]

References

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

Discovery and Preclinical Characterization of XMT-1660, an Optimized B7-H4-Targeted Antibody-Drug Conjugate for the Treatment of Cancer. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Antibody-drug conjugates for ovarian cancer: current clinical development. [2019]

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

Development of a Novel CLDN18.2-directed Monoclonal Antibody and Antibody-Drug Conjugate for Treatment of CLDN18.2-Positive Cancers. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Claudin18.2 is a novel molecular biomarker for tumor-targeted immunotherapy. [2022]

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

Population PK and Exposure-Response Relationships for the Antibody-Drug Conjugate Brentuximab Vedotin in CTCL Patients in the Phase III ALCANZA Study. [2019]