TORL-2-307-ADC for Advanced Cancer

Recruiting at 15 trial locations

Overseen By Ibrahim Qazi, PharmD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: TORL Biotherapeutics, LLC

Must not be taking: Chemotherapy, Biologics

Disqualifiers: Brain metastases, Cardiac disease, MDS, others

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

Compensation: Varies

Number of Visits: Unknown

70 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called TORL-2-307-ADC, an experimental drug, to determine its safety and effectiveness for people with advanced cancer. Researchers are testing this drug in humans for the first time to understand its effects on the body and its potential to shrink tumors. The study consists of two parts, both focusing on the drug's use alone. Suitable candidates have advanced solid tumors and can perform daily activities with minimal assistance. As a Phase 1 trial, participants will be among the first to receive this new treatment, aiding researchers in understanding its effects in people.

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.

Is there any evidence suggesting that TORL-2-307-ADC is likely to be safe for humans?

Initial findings suggest that TORL-2-307-ADC is undergoing its first human testing to assess safety. Limited information exists on how well people tolerate it due to the early stage of testing. In studies of similar treatments, researchers focus on understanding side effects and the body's response to the drug. The treatment undergoes close monitoring to ensure safety. As this marks its first human trial, staying updated with new information from the trial is crucial as more data becomes available. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about TORL-2-307-ADC because it offers a novel approach to treating advanced cancer. Unlike many traditional cancer treatments that often target rapidly dividing cells indiscriminately, this drug is an antibody-drug conjugate (ADC), which means it combines a cancer-targeting antibody with a potent anti-cancer drug. This targeted approach aims to deliver the treatment directly to cancer cells, potentially reducing harm to healthy cells and minimizing side effects. Moreover, by focusing on specific cancer cell markers, TORL-2-307-ADC might be effective against cancers that are resistant to other treatments, offering hope to patients with limited options.

What evidence suggests that TORL-2-307-ADC might be an effective treatment for advanced cancer?

Research shows that TORL-2-307-ADC targets a protein called Claudin18.2, present in some cancers, such as stomach and pancreatic cancer. Studies have shown promising results in patients with stomach cancer, where the treatment led to a 40% overall response rate (ORR) and a disease control rate (DCR) of 73.1%. This indicates that many patients experienced tumor shrinkage or halted growth. Claudin18.2 is also common in pancreatic cancer, suggesting the treatment might be effective there as well. These early findings suggest TORL-2-307-ADC could be a strong option for treating cancers with this protein. Participants in this trial will receive TORL-2-307-ADC as part of either the Monotherapy Dose Finding or the Expansion as Monotherapy treatment arms. ^{1 2 3 4 6}

Who Is on the Research Team?

Ibrahim Qazi, PharmD

Principal Investigator

TORL Biotherapeutics, LLC

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• TORL-2-307-ADC

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

Claudin18.2 (CLDN18.2) is a promising biomarker for various cancers, including gastric and breast cancer, due to its limited expression in normal tissues and abnormal expression in tumors, making it a target for specific cancer therapies.

Recent advancements in immunotherapy targeting CLDN18.2 include the development of monoclonal antibodies like zolbetuximab, bispecific antibodies, CAR-T cell therapies, and antibody-drug conjugates, highlighting its potential for effective cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Claudin18.2 is a novel molecular biomarker for tumor-targeted immunotherapy. Cao, W., Xing, H., Li, Y., et al.[2022]

The novel antibody-drug conjugate platform, Dolasynthen (DS), allows for precise optimization of drug-to-antibody ratios and site-specific conjugation, enhancing targeted drug delivery to tumors.

XMT-1660, an ADC developed using this platform targeting the B7-H4 protein, showed complete tumor regressions in various cancer models and has entered clinical development, indicating promising efficacy in treating cancers with high B7-H4 expression.

NCBI (Pubmed)

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. Toader, D., Fessler, SP., Collins, SD., et al.[2023]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11939718/

Future Landscape of Anti-Claudin 18.2 Antibodies in Gastric ... Preliminary efficacy in metastatic GAC/GEJ cancer patients with CLDN18.2 expression ≥10% (2+/3+ IHC) showed an ORR of 40% and DCR of 73.1%.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05156866

First in Human Study of TORL-2-307-ADC in Participants ... This first-in-human study will evaluate the safety, tolerability, pharmacokinetics, and antitumor activity of TORL-2-307-ADC in patients with advanced ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10951399/

Dark horse target Claudin18.2 opens new battlefield for ... Claudin18.2 is highly expressed in pancreatic cancer and is associated with the initiation, progression, metastasis and prognosis of cancer.

4. aacrjournals.org aacrjournals.org/mct/article/22/12/1365/730277/Development-of-a-Novel-CLDN18-2-directed

Development of a Novel CLDN18.2-directed Monoclonal ... In total, 12 of 23 (52.2%) of the pancreatic cancer PDXs showed some positive staining for CLDN18.2 membrane protein. CLDN18.2-307-ADC efficacy was assessed ...

5. adcreview.com adcreview.com/drugmap/torl-2-307-adc/

TORL-2-307-ADC This study is a first-in-human study designed to evaluate the safety, tolerability, pharmacokinetics, and antitumor activity of TORL-2-307-ADC in patients with ...

6. synapse.patsnap.com synapse.patsnap.com/drug/17a1033e2c0941b6955bb44fd25b6c30

TORL-2-307-ADC - Drug Targets, Indications, Patents A Phase 1, First in Human, Dose-Escalation Study of TORL-2-307-ADC in Participants With Advanced Cancer. 100 Clinical Results associated with TORL-2-307-ADC.