JANX008 for Advanced Cancer

Recruiting at 21 trial locations

Overseen By Janux Therapeutics

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Janux Therapeutics

Must not be taking: EGFR-targeted, CD3 engaging

Disqualifiers: Cardiovascular diseases, Active infection, others

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

Compensation: Varies

Number of Visits: Unknown

130 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called JANX008 (also known as EGFR-TRACTr) for individuals with certain advanced cancers. The main goal is to determine the safety of JANX008 and identify the optimal dose. Participants will receive the treatment weekly, and researchers will observe the cancer's response. This trial may suit those with advanced or metastatic cancer that hasn't improved with available treatments. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial requires that you stop any anti-cancer therapy at least 28 days before enrolling. Other medications are not specifically mentioned, so it's best to discuss with the trial team.

Is there any evidence suggesting that JANX008 is likely to be safe for humans?

Research has shown that JANX008 demonstrates promising safety results from early studies. In trials involving individuals with various advanced cancers, JANX008 was well-tolerated, even by those who had undergone multiple prior treatments, suggesting that side effects might be manageable.

Preclinical studies, conducted before human trials, also support the safety of JANX008. These tests included studies on animals similar to humans, which helped predict how the treatment might work in people. Overall, these findings offer a positive view of the safety of JANX008 for those considering participation in its clinical trials. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about JANX008 for advanced cancer because it offers a novel approach compared to existing treatments like chemotherapy, radiation, and immunotherapy. Unlike traditional options, which often attack rapidly dividing cells indiscriminately, JANX008 is designed to precisely target cancer cells, potentially reducing damage to healthy cells. This targeted approach could lead to fewer side effects and improved effectiveness in shrinking tumors. Additionally, JANX008's unique mechanism of action may overcome resistance seen in some cancers to current treatments, offering new hope for patients with advanced stages of the disease.

What evidence suggests that JANX008 might be an effective treatment for advanced cancer?

Research has shown that JANX008, the investigational treatment in this trial, holds promise for treating advanced or spreading cancer involving EGFR, a protein that can promote cancer cell growth. Early results from past studies suggest this treatment has been safe and effective for solid tumors. JANX008 targets the EGFR protein, which contributes to the growth of some cancers. In other treatments targeting EGFR, the success rate ranges from 10% to 30%, suggesting that JANX008 could also be effective for similar conditions. Initial findings indicate that JANX008 might be a viable option for patients with advanced cancers involving EGFR. Participants in this trial will join different arms to evaluate the safety and effectiveness of JANX008 at various dosages. ^{1 2 4 6 7}

Who Is on the Research Team?

Janux Therapeutics, MD

Principal Investigator

Janux Therapeutics

Are You a Good Fit for This Trial?

Adults with advanced or metastatic cancers (like lung, kidney, colorectal, or oral cancers) that have progressed despite treatment can join. They must be over 18, have at least one measurable tumor lesion and good organ function. Those who've had certain heart diseases, infections, oxygen therapy, recent cancer treatments or specific prior therapies are excluded.

Inclusion Criteria

My cancer did not respond or I couldn't tolerate all treatments known to help my type of tumor.

My cancer is confirmed to be advanced or has spread, including lung, head and neck, colon, or kidney cancer.

My organs are working well.

Exclusion Criteria

I use supplemental oxygen.

I have previously received EGFR-targeted immune therapy.

I have been treated with CD3 bispecific antibodies before.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Subjects will be dosed weekly during each 21-day cycle to determine the maximum tolerable dose

21 days per cycle

Weekly visits

Dose Expansion

Subjects will be dosed weekly at the preliminary recommended Phase 2 dose (RP2D) during each 21-day cycle

21 days per cycle

Weekly visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 4 years

What Are the Treatments Tested in This Trial?

Interventions

• JANX008

Trial Overview The trial is testing JANX008's safety and effectiveness in treating various advanced cancers expressing a protein called EGFR. It's the first time this drug is being tried in humans to see how it affects tumors and what the body does with it.

How Is the Trial Designed?

Group I: Expansion Experimental Treatment 1 Intervention

Subjects will be dosed weekly during each 21-day cycle. Subjects will be dosed at the preliminary recommended Phase 2 dose (RP2D).

Group II: Dose Escalation Experimental Treatment 1 Intervention

Subjects will be dosed weekly during each 21-day cycle. Dosage per cohort will increase to determine the maximum tolerable dose.

Group III: Backfill Expansion Experimental Treatment 1 Intervention

Subjects will be dosed weekly during each 21-day cycle. Subjects will be dosed at levels previously declared tolerable.

Who Is Running the Clinical Trial?

Janux Therapeutics

Lead Sponsor

Trials

2

Recruited

240+

Published Research Related to This Trial

EGFR-related therapies, particularly tyrosine kinase inhibitors like erlotinib and gefitinib, show a clinical benefit of 10-30% in treating non-small cell lung cancer (NSCLC), with better outcomes observed in nonsmoker Asiatic women with EGFR mutations.

Biomarkers such as EGFR mutation status and protein expression are crucial for predicting the effectiveness of EGFR therapies, aiding clinicians in making informed treatment decisions and optimizing resource use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Predictive and prognostic markers for epidermal growth factor receptor inhibitor therapy in non-small cell lung cancer. Peled, N., Yoshida, K., Wynes, MW., et al.[2022]

A new gene therapy protocol targeting cancer cells with high levels of epidermal growth factor receptor (EGFR) was developed, showing effective killing rates of 46.03% in BT-325 cells and 48.12% in Hela cells after 48 hours.

The therapy demonstrated specificity, as it did not affect JK cells that lack EGFR, indicating a targeted approach that could minimize damage to healthy cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[A strategy for targeting gene therapy against cancer mediated by epidermal growth factor receptor]. Fang, HS., Hong, M., Zhang, SZ., et al.[2023]

The bivalent recombinant immunotoxin DT390-BiscFv806 shows high cytotoxicity against glioblastoma cells and head and neck squamous cell carcinoma, with IC50 values indicating it is particularly effective against cells expressing EGFRvIII, being 4 orders of magnitude more potent against these cells than against non-expressing cells.

In animal studies, DT390-BiscFv806 significantly inhibited tumor growth in models with U87-EGFRvIII and U87 tumors, achieving growth inhibition rates of 76.3% and 59.4%, respectively, suggesting its potential as a targeted cancer therapy for tumors with high EGFR expression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A bivalent recombinant immunotoxin with high potency against tumors with EGFR and EGFRvIII expression. Meng, J., Liu, Y., Gao, S., et al.[2023]

EGFR-targeting agents like C225 and ZD1839 show promise in treating cancers such as non-small cell lung cancer (NSCLC) and head and neck squamous cell carcinoma (HNSCC), with C225 demonstrating synergy with chemotherapy and radiation in preclinical models.

Despite initial positive responses in phase I trials, large phase III studies of ZD1839 combined with chemotherapy did not show an increase in survival for advanced NSCLC patients, highlighting the need for further research into effective treatment combinations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The epidermal growth factor receptor pathway and its inhibition as anticancer therapy. Janmaat, ML., Giaccone, G.[2022]

EGFR-targeted therapies, such as cetuximab and erlotinib, are important treatments for metastatic cancers, specifically colorectal cancer and non-small cell lung cancer, respectively.

Despite both targeting the same EGFR receptor, cetuximab (a monoclonal antibody) and erlotinib (a small-molecule TKI) have different mechanisms of action, which influence their dosing, toxicity, and potential for use in combination therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical implications of the mechanism of epidermal growth factor receptor inhibitors. Marshall, J.[2018]

The peptide-based therapeutic cSNX1.3 effectively promotes cell death in EGFR-expressing breast cancer models, leading to significant tumor regression in mice without causing observable toxicity.

cSNX1.3 works by binding to the C-terminus of the EGFR kinase domain, inhibiting its nuclear localization and specifically targeting transformed cancer cells with wildtype EGFR, while sparing normal cells and those with mutant EGFR.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sorting nexin-dependent therapeutic targeting of oncogenic epidermal growth factor receptor. Atwell, B., Chen, CY., Christofferson, M., et al.[2023]

Epidermal growth factor receptor (EGFR) targeting agents, such as erlotinib and cetuximab, are effective treatments for various solid tumors, including non-small cell lung carcinoma and metastatic colorectal carcinoma, with increasing use anticipated for other cancers.

These drugs have a unique safety profile with minimal hematological toxicity, but they can cause significant skin and gastrointestinal side effects, which can be managed to improve patient compliance and maintain treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cutaneous reactions to anticancer agents targeting the epidermal growth factor receptor: a dermatology-oncology perspective. Lacouture, ME., Melosky, BL.[2018]

Epidermal growth factor receptor (EGFR) inhibitors like erlotinib and gefitinib have shown established clinical activity in treating non-small cell lung cancer, with newer agents like ZD6474 showing promising antitumor activity in clinical trials.

Several new EGFR inhibitors are in advanced testing, indicating that EGFR is a validated target for cancer treatment, and future research will focus on their effectiveness in patients who have not responded to existing EGFR therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Epidermal growth factor receptor inhibitors in development for the treatment of non-small cell lung cancer. Heymach, JV., Nilsson, M., Blumenschein, G., et al.[2018]

Epidermal growth factor receptor (EGFR) inhibitors, including monoclonal antibodies like cetuximab and tyrosine kinase inhibitors like gefitinib, have been approved for cancer treatment, highlighting their efficacy as targeted therapies in epithelial cancers.

Understanding the biology of EGFR interactions can lead to more selective cancer treatments with reduced side effects, although further research is needed to optimize combinations with other therapies and identify the best patient candidates for these treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biology of interactions: antiepidermal growth factor receptor agents. Harari, PM., Allen, GW., Bonner, JA.[2022]

EGFR is a key player in the growth of non-small cell lung cancer (NSCLC), and therapies targeting EGFR, such as cetuximab and small-molecule inhibitors like erlotinib, have shown antitumor activity in previously treated NSCLC patients.

Erlotinib not only improved quality of life but also extended median survival compared to best supportive care, highlighting its efficacy as a single-agent therapy for NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inhibition of the epidermal growth factor receptor in combined modality treatment for locally advanced non-small cell lung cancer. Ready, N.[2019]

The combination of erlotinib and ruxolitinib was well tolerated in 22 patients with EGFR-mutant lung cancers, showing no dose-limiting toxicities and a maximum tolerated dose of 150 mg daily for erlotinib and 20 mg twice daily for ruxolitinib.

Despite the treatment being well tolerated, it was largely ineffective, with only one partial response observed and a median progression-free survival of just 2.2 months, indicating a need for more effective strategies against resistance in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase 1/2 Trial of Ruxolitinib and Erlotinib in Patients with EGFR-Mutant Lung Adenocarcinomas with Acquired Resistance to Erlotinib. Yu, HA., Perez, L., Chang, Q., et al.[2021]

Citations

1. investors.januxrx.com investors.januxrx.com/investor-media/news/news-details/2024/Janux-Announces-Encouraging-Safety-and-Efficacy-Data-in-Ongoing-Dose-Escalation-Trials-for-PSMAxCD3-TRACTr-JANX007-in-mCRPC-and-EGFRxCD3-TRACTr-JANX008-in-Solid-Tumors/default.aspx

Janux Announces Encouraging Safety and Efficacy Data in ... “These clinical data show encouraging safety and efficacy with JANX007 in metastatic castration-resistant prostate cancer and with JANX008 in ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05783622

Study of JANX008 in Subjects With Advanced or Metastatic ... Study of JANX008 in Subjects With Advanced or Metastatic Solid Tumor Malignancies. ClinicalTrials.gov ID NCT05783622. Sponsor Janux Therapeutics.

3. withpower.com withpower.com/trial/phase-1-carcinoma-2-2023-4a214

JANX008 for Advanced Cancer EGFR-related therapies, particularly tyrosine kinase inhibitors like erlotinib and gefitinib, show a clinical benefit of 10-30% in treating non-small cell lung ...

4. urologytimes.com urologytimes.com/view/immunotherapies-show-safety-and-efficacy-in-mcrpc-renal-cell-carcinoma

Immunotherapies show safety and efficacy in mCRPC ... These clinical data show encouraging safety and efficacy with JANX007 in metastatic castration-resistant prostate cancer and with JANX008 in late-stage solid ...

5. firstwordpharma.com firstwordpharma.com/story/5956573

Janux Therapeutics Initiates Phase 1b Expansion Studies ... Janux's second clinical candidate, JANX008, is a TRACTr that targets epidermal growth factor receptor (EGFR) and is being studied in a Phase 1 ...

6. aacrjournals.org aacrjournals.org/cancerimmunolres/article/10/12_Supplement/B04/711256/Abstract-B04-Preclinical-activity-and-safety

Abstract B04: Preclinical activity and safety profile or JANX008 ... The pharmacokinetic and safety profile of JANX008 was evaluated in non-human primate studies. Results: JANX008 target engagement was cleavage- ...

7. januxrx.com januxrx.com/egfr-tractr-janx008/

T Cell Immuno-oncology | EGFR-TRACTr (JANX008) JANX008 clinical data has displayed differentiated safety and encouraging signs of efficacy in heavily pretreated subjects with different EGFR+ solid tumor ...