TORL-2-307-MAB for Advanced Cancer

Not currently recruiting at 11 trial locations

Overseen By Stephen Letrent, PharmD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: TORL Biotherapeutics, LLC

Must not be taking: Chemotherapy, Biologics

Disqualifiers: Brain metastases, Cardiac disease, others

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

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 TORL-2-307-MAB, an experimental therapy for individuals with advanced cancer. The goal is to determine the treatment's safety, its behavior in the body, and its potential to shrink tumors. The study consists of two parts, both evaluating the treatment independently. Individuals with measurable advanced solid tumors and good overall health may qualify for this trial. As a Phase 1 trial, participants will be among the first to receive this new treatment, aiding researchers in understanding its effects in humans.

Will I have to stop taking my current medications?

The trial requires that you have not received any chemotherapeutic, investigational, or other cancer therapies within 14 days for small molecules and 28 days for biologics before starting the study. It does not specify about other medications, so it's best to discuss with the trial team.

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

Research shows that the treatment TORL-2-307-MAB remains in the early testing phase. As it is being tested in humans for the first time, no safety data from previous human trials exists. Researchers are still learning about its safety and tolerability.

In early trials like this, the main goal is to determine the treatment's safety for humans and identify any side effects. Researchers closely monitor participants for any unwanted effects, and these trials are crucial for understanding how the body responds to the treatment.

While specific safety data on TORL-2-307-MAB is not yet available, the ongoing study will help gather this important information. Participants in this trial will assist researchers in learning more about the drug's safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about TORL-2-307-MAB because it represents a novel approach to treating advanced cancer. Unlike traditional options that often target cancer cells broadly, TORL-2-307-MAB is designed to precisely target specific cancer cell markers, potentially increasing effectiveness while minimizing damage to healthy cells. This targeted action could lead to fewer side effects and improved outcomes for patients. If successful, TORL-2-307-MAB might offer a more personalized and efficient treatment option compared to the current standard therapies.

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

Research shows that TORL-2-307-MAB is a monoclonal antibody, a type of protein designed to target and attack cancer cells while sparing normal cells. Although human data is not yet available to confirm its effectiveness, early signs are promising. Similar treatments have shown potential in targeting specific proteins on cancer cells, such as Claudin 18.2, commonly found in stomach and pancreatic cancers. Monoclonal antibodies have successfully treated other cancer types, offering hope for TORL-2-307-MAB. Further studies will clarify its effectiveness for patients with advanced cancer. ^{1 2 3 4 6}

Who Is on the Research Team?

Stephen Letrent, PharmD, PhD

Principal Investigator

TORL Biotherapeutics, LLC

Are You a Good Fit for This Trial?

This trial is for adults with advanced solid tumors, including pancreatic, stomach, and gastroesophageal junction adenocarcinoma. Participants must have measurable disease and be in good physical condition (ECOG 0-1). They can't join if they've had certain blood cancers, untreated brain metastases, unresolved toxic effects from past treatments (except hair loss), recent cancer therapies within the last 14 to 28 days depending on the therapy type, serious health issues or infections, are pregnant/breastfeeding, have significant heart disease or another cancer within the last three years.

Inclusion Criteria

I am fully active or can carry out light work.

My organs are working well.

My cancer is in an advanced stage and not just in one place.

Exclusion Criteria

I haven't taken cancer treatment drugs within the last 14 days for small molecules or 28 days for biologics.

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

I am not pregnant or breastfeeding.

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-MAB to evaluate safety, tolerability, and pharmacokinetics

28 days

Multiple visits for dose escalation and monitoring

Expansion Treatment

Participants receive TORL-2-307-MAB at the recommended phase 2 dose to further assess safety and efficacy

up to 2 years

Regular visits for treatment and monitoring

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-MAB

Trial Overview The study tests a new drug called TORL-2-307-MAB for safety and effectiveness against advanced cancers. It's a first-in-human study which means it's the first time this drug is being tried in people. The trial will also look at how the body processes the drug and its impact on tumor size.

How Is the Trial Designed?

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

TORL-2-307-MAB

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

TORL-2-307-MAB

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

Antibody-drug conjugates (ADCs) offer targeted therapy for advanced cancers, utilizing toxins that are otherwise unavailable, but they can cause significant toxicities such as peripheral neuropathy and left ventricular dysfunction.

Risk minimization strategies for managing these toxicities are similar to those used for standard chemotherapy, making them familiar and feasible for healthcare providers treating patients with ADCs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk Minimization of Antibody-Drug Conjugates in Oncology: A Review. Lievano, FA., Scarazzini, LJ., Tyczynski, JE., et al.[2022]

In a randomized phase II study involving 149 patients with platinum-sensitive recurrent advanced ovarian cancer, the addition of pertuzumab to carboplatin-based chemotherapy did not significantly improve progression-free survival (PFS) compared to chemotherapy alone.

Pertuzumab was well tolerated, showing no increase in cardiac adverse events, indicating it is a safe option to combine with chemotherapy despite not enhancing efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized phase II study evaluating the combination of carboplatin-based chemotherapy with pertuzumab versus carboplatin-based therapy alone in patients with relapsed, platinum-sensitive ovarian cancer. Kaye, SB., Poole, CJ., Dańska-Bidzińska, A., et al.[2022]

Datopotamab deruxtecan (Dato-DXd) is a novel antibody-drug conjugate that effectively targets TROP2, leading to significant antitumor activity and apoptosis in TROP2-expressing tumors, as demonstrated in various human cancer cell lines and xenograft models.

The safety profiles of Dato-DXd were found to be acceptable in preclinical studies involving rats and cynomolgus monkeys, suggesting it could be a promising treatment option for patients with TROP2-expressing tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Datopotamab Deruxtecan, a Novel TROP2-directed Antibody-drug Conjugate, Demonstrates Potent Antitumor Activity by Efficient Drug Delivery to Tumor Cells. Okajima, D., Yasuda, S., Maejima, T., et al.[2023]

Monoclonal antibodies (mAbs) are increasingly being used in cancer therapy, targeting malignant cells and blocking survival signals, which can lead to direct cancer cell death and stimulate immune responses against tumors.

Regulatory agencies are approving new mAbs annually, and existing ones are being repurposed for additional cancer types as new clinical trial results emerge, highlighting their growing role in oncology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trial watch: Tumor-targeting monoclonal antibodies for oncological indications. Vacchelli, E., Pol, J., Bloy, N., et al.[2021]

In a phase 3 trial with 569 patients, the addition of daratumumab to lenalidomide and dexamethasone significantly improved progression-free survival, with only 18.5% of patients experiencing disease progression compared to 41.0% in the control group.

Daratumumab also resulted in a higher overall response rate (92.9% vs. 76.4%) and a greater percentage of patients achieving minimal residual disease status (22.4% vs. 4.6%), although it was associated with a higher incidence of neutropenia and infusion-related reactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daratumumab, Lenalidomide, and Dexamethasone for Multiple Myeloma. Dimopoulos, MA., Oriol, A., Nahi, H., et al.[2022]

Subcutaneous daratumumab, a monoclonal antibody for multiple myeloma, has been shown to be non-inferior to the traditional intravenous formulation, providing similar efficacy with the added benefits of reduced infusion times and lower rates of infusion-related reactions.

Clinical trials, including PAVO, COLUMBA, and PLEIADES, support the use of subcutaneous daratumumab in both newly diagnosed and relapsed refractory myeloma patients, indicating it may improve patient quality of life and decrease healthcare resource use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An evaluation of subcutaneous daratumumab for the treatment of multiple myeloma. Paul, B., Atrash, S., Bhutani, M., et al.[2021]

Demcizumab, a humanized monoclonal antibody targeting the Notch ligand DLL4, was generally well tolerated in a phase I trial with 55 patients, showing disease stabilization and some tumor size reduction at doses up to 5 mg weekly.

The most common treatment-related adverse event was hypertension (47%), and prolonged use at higher doses raised concerns about congestive heart failure, indicating the need for careful monitoring in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I dose escalation and expansion study of the anticancer stem cell agent demcizumab (anti-DLL4) in patients with previously treated solid tumors. Smith, DC., Eisenberg, PD., Manikhas, G., et al.[2018]

Citations

1. 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 ...

2. withpower.com withpower.com/trial/phase-1-pancreatic-neoplasms-11-2021-a035b

TORL-2-307-MAB for Advanced Cancer · Info for Participants What data supports the effectiveness of the drug TORL-2-307-MAB for advanced cancer? Monoclonal antibodies (special proteins designed to target specific cells) ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05159440?term=mab%20in&viewType=Table&checkSpell=&rank=7

NCT05159440 | First in Human Study of TORL-2-307-MAB ... Received prior chemotherapeutic, investigational, or other therapies for the treatment of cancer within 14 days with small molecule and within 28 days with ...

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

Future Landscape of Anti-Claudin 18.2 Antibodies in Gastric ... First described in the phase II MONO trial, zolbetuximab showed modest efficacy as a single agent in the treatment of patients with CLDN18.2- ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S0304383524007572

Emerging targets in gastric and pancreatic cancer TORL-2-307-MAB is in a phase 1 clinical trial (NCT05159440) evaluating its safety and efficacy in advanced gastric, pancreatic, and ...

6. 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 ...