TORL-2-307-MAB for Advanced Cancer

Recruiting at 7 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

70 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial will test a new drug called TORL-2-307-MAB in patients with advanced cancer. It aims to see if the drug is safe, how the body handles it, and if it can help fight tumors.

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.

What data supports the effectiveness of the drug TORL-2-307-MAB for advanced cancer?

Monoclonal antibodies (special proteins designed to target specific cells) like TORL-2-307-MAB are increasingly used in cancer treatment because they can directly attack cancer cells or help the immune system do so. Many such antibodies have been approved for cancer treatment, showing their potential effectiveness. ^{1 2 3 4 5}

What safety data exists for TORL-2-307-MAB or similar treatments?

Antibody-drug conjugates (ADCs) like TORL-2-307-MAB can have side effects such as nerve damage, lung, skin, liver, and eye issues, high blood sugar, heart problems, and fluid-related events. These side effects are managed with standard medical practices similar to those used for other cancer treatments. ^{6 7 8 9 10}

How is the drug TORL-2-307-MAB different from other cancer treatments?

TORL-2-307-MAB is a monoclonal antibody (a lab-made protein that can bind to specific targets in the body) designed to target cancer cells more effectively by recognizing specific antigens on their surface. This drug may offer a more precise approach compared to traditional treatments, potentially leading to better targeting of cancer cells and fewer side effects. ^{4 11 12 13 14}

Research Team

Stephen Letrent, PharmD, PhD

Principal Investigator

TORL Biotherapeutics, LLC

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

References

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

Association Between Low Trough Levels of Vedolizumab During Induction Therapy for Inflammatory Bowel Diseases and Need for Additional Doses Within 6 Months. [2022]

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

Isatuximab for relapsed/refractory multiple myeloma: review of key subgroup analyses from the Phase III ICARIA-MM study. [2022]

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

Daratumumab, Lenalidomide, and Dexamethasone for Multiple Myeloma. [2022]

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

Trial watch: Tumor-targeting monoclonal antibodies for oncological indications. [2021]

5. England pubmed.ncbi.nlm.nih.gov

An evaluation of subcutaneous daratumumab for the treatment of multiple myeloma. [2021]

6. New Zealand pubmed.ncbi.nlm.nih.gov

Risk Minimization of Antibody-Drug Conjugates in Oncology: A Review. [2022]

7. England 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. [2022]

8. United States 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. [2023]

9. United States 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. [2018]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Imaging-Guided Therapy Simultaneously Targeting HER2 and EpCAM with Trastuzumab and EpCAM-Directed Toxin Provides Additive Effect in Ovarian Cancer Model. [2021]

11. Italy pubmed.ncbi.nlm.nih.gov

Monoclonal antibodies for medical oncology: a few critical perspectives. [2021]

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

Radioimmunolocalization of human carcinoma xenografts with B72.3 second generation monoclonal antibodies. [2015]

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

New chimeric anti-pancarcinoma monoclonal antibody with superior cytotoxicity-mediating potency. [2016]

14. Netherlands pubmed.ncbi.nlm.nih.gov

Antibodies in oncology. [2011]