REC-1245 for Cancer

(DAHLIA Trial)

Recruiting at 5 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Recursion Pharmaceuticals Inc.

Disqualifiers: GI malabsorption, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: up to 24 months

85 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new drug, REC-1245, to determine its safety and effectiveness in treating certain advanced cancers. Researchers aim to understand how the body processes the drug and its impact on cancer cells. The study will test various doses to identify the most effective amount. This trial may suit individuals with advanced solid tumors or specific types of lymphoma who have not responded to other treatments. 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 information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that REC-1245 is likely to be safe for humans?

Research is examining how REC-1245 affects solid tumors, particularly those that are difficult to operate on or have spread. Earlier studies tested the body's ability to handle REC-1245, focusing on identifying any side effects and their severity.

Since REC-1245 is in the early stages of testing, detailed safety information for humans might not be fully available yet. However, these early phases ensure the treatment's safety, so researchers closely monitor for any negative effects. If REC-1245 progresses to later stages, it typically indicates a reasonable level of safety in these initial tests.

For those considering joining a trial, it's important to know that safety is a top priority, and any trial will have measures in place to quickly address any concerns. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for cancer?

REC-1245 is unique because it potentially offers a new approach to treating cancer by targeting specific pathways that current standard treatments, like chemotherapy and immunotherapy, may not address. Researchers are particularly excited about its novel mechanism of action, which could more precisely target cancer cells while sparing healthy cells. This could lead to fewer side effects and improved effectiveness compared to existing therapies. Additionally, REC-1245's flexible dosing options in early phases suggest the possibility of tailoring treatment to individual patient needs, which is a significant step forward in personalized cancer care.

What evidence suggests that REC-1245 might be an effective treatment for cancer?

Studies have shown that REC-1245 targets tumors with specific weaknesses in DNA repair, making it potentially effective against certain types of cancer. Early research suggests that REC-1245 can reduce the growth of tumors struggling with DNA repair. REC-1245 mimics the loss of a protein called CDK12, which aids in DNA repair. This trial will explore REC-1245 across various phases, including dose escalation and confirmation, to determine its effectiveness and safety. Although research in humans remains in the early stages, these findings suggest a promising approach for treating solid tumors. ^{2 3 4 6 7}

Are You a Good Fit for This Trial?

This trial is for individuals with cancers that can't be removed by surgery, are locally advanced, or have spread to other parts of the body. It's open to those with primary cancer, oral and head & neck cancers, or lymphoma.

Inclusion Criteria

I am fully active and can carry on all my pre-disease activities without restriction.

My cancer has worsened or returned after treatment, or I can't tolerate standard cancer treatments.

My cancer is advanced and cannot be removed by surgery.

Exclusion Criteria

I have been treated with an RBM39 degrader before.

I have serious stomach or nutrient absorption problems.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive REC-1245 orally on a once daily schedule for up to 2 years

up to 24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• REC-1245

Trial Overview The study is testing REC-1245, a new medication given orally once daily. The goal is to assess its safety and how well it works in treating various advanced cancers.

How Is the Trial Designed?

Group I: Phase 2 Experimental Treatment 1 Intervention

At recommended Phase 2 dose (RP2D)

Group II: Phase 1b Dose #2 Experimental Treatment 1 Intervention

Dose #2 TBD

Group III: Phase 1b Dose #1 Experimental Treatment 1 Intervention

Dose Confirmation

Group IV: Phase 1a Experimental Treatment 1 Intervention

Dose Escalation

REC-1245 is already approved in United States, European Union for the following indications:

Approved in United States as REC-1245 for:

• None approved; currently in Phase 1/2 clinical trial for biomarker-enriched solid tumors and lymphoma

Approved in European Union as REC-1245 for:

• None approved; currently in Phase 1/2 clinical trial for biomarker-enriched solid tumors and lymphoma

Who Is Running the Clinical Trial?

Recursion Pharmaceuticals Inc.

Lead Sponsor

Trials

6

Recruited

450+

Published Research Related to This Trial

In a study involving 299 patients with refractory metastatic colorectal cancer, different dosing schedules of regorafenib were evaluated for safety, showing that 60% of patients in the standard dose group experienced severe treatment-related adverse events, compared to 55% and 54% in the lower dose and intermittent dosing groups, respectively.

The alternative dosing schedules were found to be feasible and safe, with the intermittent dosing showing a potential numerical improvement in managing severe adverse events, particularly during the initial treatment cycles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomised phase 2 study comparing different dose approaches of induction treatment of regorafenib in previously treated metastatic colorectal cancer patients (REARRANGE trial). Argilés, G., Mulet, N., Valladares-Ayerbes, M., et al.[2023]

Regorafenib is the first approved tyrosine kinase inhibitor for metastatic colorectal cancer, showing significant improvements in progression-free and overall survival in patients who had previously undergone multiple lines of chemotherapy and targeted therapies, based on results from two phase III trials.

While regorafenib has a safety profile similar to other tyrosine kinase inhibitors, it is associated with specific adverse events like hand-foot skin reaction and hypertension, which can be managed effectively through patient education and timely dose adjustments, allowing patients to continue benefiting from the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improving patient outcomes with regorafenib for metastatic colorectal cancer - patient selection, dosing, patient education, prophylaxis, and management of adverse events. Hofheinz, RD., Arnold, D., Kubicka, S., et al.[2015]

Regorafenib (REG) was associated with a high incidence of renal adverse drug reactions (ADRs), accounting for 93.1% of 379 reports, with significant safety signals for conditions like chromaturia, hydronephrosis, and acute kidney injury.

Encorafenib (ENC) also showed potential renal toxicity, particularly with acute kidney injury and dysuria, indicating that both drugs may pose risks to kidney health in patients with metastatic colorectal cancer (mCRC) that warrant further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Renal Disorders with Oral Tyrosine Kinase Inhibitors in Metastatic Colorectal Cancer: An Analysis from the FDA Adverse Event Reporting System Database. Russo, G., Barbieri, MA., Sorbara, EE., et al.[2023]

A meta-analysis of 53 Phase II/III/IV trials involving nearly 20,000 patients revealed that molecular target anticancer drugs significantly increase the risk of serious adverse events (SAEs) by 57% and fatal adverse events (FAEs) by 51% compared to placebo.

The overall incidence rates for SAEs and FAEs were found to be 26.9% and 2.3%, respectively, highlighting the need for careful monitoring and preventive measures for patients receiving these treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk of serious adverse event and fatal adverse event with molecular target anticancer drugs in cancer patients: A meta-analysis. Wang, Z., Yang, X., Wang, J., et al.[2020]

The PRO-CTCAE tool allows breast cancer patients to report their own symptoms during chemotherapy, providing real-time feedback to clinicians, which could improve patient care.

This national study aims to assess the impact of electronic PRO-CTCAE reporting on critical treatment outcomes such as dose reduction, hospitalization, and febrile neutropenia, marking a significant step in understanding patient-reported outcomes in cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Routine surveillance for symptomatic toxicities with real-time clinician reporting in Danish breast cancer patients-Organization and design of the first national, cluster randomized trial using the Patient-Reported Outcomes version of Common Terminology Criteria for Adverse Events (PRO-CTCAE). Pappot, H., Baeksted, C., Knoop, A., et al.[2019]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06678659

NCT06678659 | A Study of REC-1245 in Participants With ... The purpose of this study is to investigate the safety, tolerability and pharmacokinetics of REC-1245 for the treatment of participants with unresectable ...

2. genengnews.com genengnews.com/topics/artificial-intelligence/recursion-halts-four-pipeline-programs-sharpening-cancer-rare-disease-focus/

Recursion Halts Four Pipeline Programs, Sharpening ... A key example, according to Recursion, is its oncology candidate REC-1245, which is designed to treat biomarker-enriched solid tumors and ...

3. ir.recursion.com ir.recursion.com/news-releases/news-release-details/recursion-announces-first-patient-dosed-phase-12-clinical-study

Recursion announces first patient dosed in Phase 1/2 ... REC-1245 was characterized to selectively mimic the phenotype associated with CDK12 loss of function, and is an alternative target for ...

4. recursion.com recursion.com/pipeline

Recursion's Drug Discovery Pipeline Early preclinical data shows REC-1245 reduces viability in tumors characterized by replication stress and DNA repair vulnerabilities (DDR defects) across ...

5. trialfinder.panfoundation.org trialfinder.panfoundation.org/en-US/trial/listing/554215

A Study of REC-1245 in Participants With Unresectable, ... This is a multi-center, open-label study to investigate the safety, tolerability, PK, PD, and preliminary activity of REC-1245 administered orally on a once ...

6. connect.careboxhealth.com connect.careboxhealth.com/en-US/trial/listing/554215

A Study of REC-1245 in Participants With Unresectable ... This is a multi-center, open-label study to investigate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary activity of ...

7. ctv.veeva.com ctv.veeva.com/study/a-study-of-rec-1245-in-participants-with-unresectable-locally-advanced-or-metastatic-cancer

A Study of REC-1245 in Participants With Unresectable ... This is a multi-center, open-label study to investigate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), ...