QTX3046 + Cetuximab for Solid Tumors

Not currently recruiting at 4 trial locations

Overseen By Quanta Therapeutics Clinical Trials

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Quanta Therapeutics

Must not be taking: KRAS inhibitors

Disqualifiers: Brain metastasis, Cardiovascular 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 the safety of a new drug, QTX3046, either alone or with cetuximab (a type of cancer treatment), for individuals with advanced solid tumors. It targets those whose cancer has a specific mutation (KRAS G12D) and who have already tried at least one other treatment. Participants should have a type of cancer that can be measured and tracked over time. The trial helps researchers determine how the new treatment works and its safety for future use. As a Phase 1 trial, participants will be among the first to receive this 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 this trial's treatments are likely to be safe?

Research shows that QTX3046 is being tested for safety and tolerability, both alone and with cetuximab. As a Phase 1 study, researchers are still gathering safety information. Phase 1 trials primarily focus on understanding a drug's safety and patient reactions.

Currently, no specific safety results for QTX3046 have emerged from these early studies. However, cetuximab, used with QTX3046, has FDA approval for other uses. It is generally safe but can cause common side effects like skin problems, diarrhea, and tiredness.

Prospective participants should know that early-phase studies primarily examine safety and side effects. As more data becomes available, researchers will better understand how well patients tolerate QTX3046. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about QTX3046 because it offers a novel approach to treating solid tumors. Unlike traditional treatments that primarily rely on chemotherapy or radiation, QTX3046 is designed to be taken orally, which can be more convenient for patients. Additionally, it works by inhibiting specific pathways that cancer cells use to grow, potentially making it more targeted and less toxic than standard therapies. The combination of QTX3046 with cetuximab, an established cancer drug, might enhance its effectiveness, providing a fresh strategy to tackle stubborn tumors.

What evidence suggests that this trial's treatments could be effective for solid tumors?

Research has shown that QTX3046 is a promising new treatment for solid tumors with KRASG12D mutations. This treatment specifically targets the KRASG12D mutation, common in many cancers, and helps stop cancer growth. In this trial, some participants will receive QTX3046 alone, while others will receive it with cetuximab. Cetuximab targets a protein called EGFR, which is involved in tumor growth. The combination aims to fight cancer cells in multiple ways. Early results suggest that this combination might be particularly effective for treating solid tumors with these mutations. ^{1 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for adults with advanced solid tumors that have a specific genetic change called KRAS G12D mutation. They must have tried at least one treatment before and their disease should be measurable by medical imaging. People can't join if they don't meet the testing requirements or other specifics not listed here.

Inclusion Criteria

I have advanced cancer with a history of treatment and my disease can be measured.

Measurable disease per RECIST v1.1 for Part 2 and 3

My cancer has a KRAS G12D mutation confirmed by a certified test.

Exclusion Criteria

I have a serious heart condition.

I have active brain metastasis or carcinomatous meningitis.

I have been treated with a KRAS inhibitor before.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

QTX3046 is administered orally at escalating doses, with or without cetuximab, to determine safety and tolerability

3 weeks

Multiple visits for dose escalation monitoring

Dose Expansion

QTX3046 is administered at the recommended phase 2 dose, with or without cetuximab, to further evaluate safety and efficacy

up to 2 years

Regular visits for treatment and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Cetuximab
• QTX3046

Trial Overview The study is looking at how safe and tolerable QTX3046 is, either on its own or when used together with another cancer drug called Cetuximab. It's an early-stage (Phase 1) trial to see what effects these treatments have on patients.

How Is the Trial Designed?

Group I: Part 3: QTX3046 dose expansion in combination with cetuximab Experimental Treatment 2 Interventions

QTX3046 will be administered orally at the recommended phase 2 dose (RP2D) in combination with intravenous cetuximab based on cohort assignment

Group II: Part 2: QTX3046 monotherapy dose expansion Experimental Treatment 1 Intervention

QTX3046 will be administered orally at the recommended phase 2 dose (RP2D) based on cohort assignment

Group III: Part 1b: QTX3046 dose escalation in combination with cetuximab Experimental Treatment 2 Interventions

QTX3046 will be administered orally at escalating doses as defined in the protocol in combination with intravenous cetuximab based on dose level assignment

Group IV: Part 1a: QTX3046 monotherapy dose escalation Experimental Treatment 1 Intervention

QTX3046 will be administered orally at escalating doses as defined in the protocol based on dose level assignment

Who Is Running the Clinical Trial?

Quanta Therapeutics

Lead Sponsor

Trials

3

Recruited

730+

Published Research Related to This Trial

Cetuximab, a monoclonal antibody used to treat various cancers, can cause serious side effects, including interstitial lung disease, as demonstrated in a case where a patient developed this condition within the first 4 weeks of treatment and ultimately died.

This case emphasizes the need for healthcare professionals to be aware of the potential for early and fatal pulmonary complications associated with cetuximab, which are not commonly reported in the literature.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A case of fatal cetuximab-induced interstitial lung disease during the first weeks of treatment. Shablak, A., Conn, A.[2021]

Cetuximab, a monoclonal antibody used to treat various cancers, has been associated with a rare side effect of aseptic meningitis, occurring in less than 1% of patients.

This case report details the first known instance of aseptic meningitis in a patient with metastatic colon cancer who had previously been treated with cetuximab, highlighting the importance of awareness among clinicians regarding this potential adverse event.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A case of aseptic meningitis in a cetuximab-experienced patient with metastatic colon cancer. Rohrer, CL., Grullon, Z., George, SK., et al.[2018]

Cetuximab, an anti-cancer drug that targets the epidermal growth factor receptor (EGF-R), can cause acneiform eruptions as a secondary side effect in patients with adenocarcinoma.

The skin reactions, characterized by folliculitis, responded well to topical treatments like benzoyl peroxide and erythromycin gel, indicating that these side effects can be effectively managed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Two cases of acneiform eruption induced by inhibitor of epidermal growth factor receptor. Gencoglan, G., Ceylan, C.[2018]

Cetuximab is an effective treatment for patients with metastatic colorectal cancer (mCRC) who have wild-type KRAS, and its use has been supported by various clinical trials assessing its impact on patient outcomes and quality of life.

The identification of KRAS mutation status is crucial for selecting patients who are most likely to benefit from cetuximab, enhancing the treatment's efficacy in managing unresectable mCRC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of cetuximab in current treatment of metastatic colorectal cancer. Sotelo Lezama, MJ., Sastre Valera, J., Díaz-Rubio García, E.[2018]

The study successfully developed (86)Y-CHX-A''-DTPA-cetuximab, a radiolabeled monoclonal antibody that effectively targets HER1-expressing tumors, demonstrating high tumor uptake and low nonspecific organ clearance in mouse models.

Quantitative PET imaging showed that (86)Y-CHX-A''-DTPA-cetuximab can visualize tumors effectively, with a strong correlation between PET results and biodistribution studies, indicating its potential for clinical use in imaging HER1-expressing cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PET imaging of HER1-expressing xenografts in mice with 86Y-CHX-A''-DTPA-cetuximab. Nayak, TK., Regino, CA., Wong, KJ., et al.[2021]

In a pilot phase II study involving 22 patients with advanced squamous cell head and neck cancer, the combination of cetuximab with chemoradiotherapy showed promising preliminary efficacy, with a 3-year overall survival rate of 76%.

Despite the encouraging results, the study was halted due to significant adverse events, including two deaths and other serious complications, highlighting the need for further investigation into the safety of this treatment regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Concurrent cetuximab, cisplatin, and concomitant boost radiotherapy for locoregionally advanced, squamous cell head and neck cancer: a pilot phase II study of a new combined-modality paradigm. Pfister, DG., Su, YB., Kraus, DH., et al.[2022]

In a study of 34 wild-type KRAS metastatic colorectal cancer patients treated with cetuximab, the overall response rate was 30.30%, indicating that cetuximab can provide clinical benefits even in patients who are resistant to other treatments.

Clinically relevant skin toxicity (grades 2-4) was associated with significantly better treatment responses, with an overall response rate of 80% in patients experiencing higher toxicity compared to only 20% in those with lower toxicity, suggesting that skin reactions may serve as a predictor of treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical benefit of cetuximab and prognostic value of cetuximab-related skin toxicity in metastatic colorectal cancer: a single institution analysis. Cvetanovic, A., Vrbic, S., Filipovic, S., et al.[2016]

Cetuximab has demonstrated significant efficacy in treating metastatic colorectal cancer, achieving a partial response in 10.8% of patients receiving it alone and 22.9% when combined with irinotecan, based on a Phase III trial involving 329 patients.

The drug is generally well tolerated, with common side effects like acnelike rash and hypersensitivity reactions, but the lack of reliable predictive markers for patient selection remains a challenge for its clinical use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cetuximab: an epidermal growth factor receptor monoclonal antibody for the treatment of colorectal cancer. Wong, SF.[2022]

In a study of 66 colorectal cancer patients treated with cetuximab, 93.8% of those who experienced severe skin toxicity (grade 2-3) showed a positive response to the treatment, indicating a strong correlation between skin toxicity and treatment efficacy.

Cetuximab is effective for KRAS wild-type colorectal cancer patients, and the presence of skin toxicity may serve as a predictive factor for a beneficial response to the therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Evaluation of skin toxicity caused by cetuximab related to its clinical response]. Osuga, T., Kogawa, T., Kimura, T., et al.[2018]

Cetuximab is a chimeric monoclonal antibody that targets the epidermal growth-factor receptor (EGFR) and has been clinically approved in Europe for treating metastatic colorectal cancer and locally advanced head and neck cancer since 2004 and 2006, respectively.

The review discusses cetuximab's established role in colorectal cancer treatment, ongoing studies, and future challenges, highlighting its significance as the leading anti-EGFR monoclonal antibody in clinical evaluation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cetuximab: appraisal of a novel drug against colorectal cancer. Hildebrandt, B., le Coutre, P., Nicolaou, A., et al.[2019]

Cetuximab, an anti-EGF receptor monoclonal antibody, showed no dose-limiting toxicities in Phase I studies and was well-tolerated, with common side effects including skin toxicity, diarrhea, and fatigue.

While Phase III trials indicated only a small overall survival benefit when cetuximab was added to chemotherapy, a subgroup analysis suggested a significant survival advantage in patients with high EGF receptor expression, potentially paving the way for its use in advanced non-small-cell lung cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cetuximab in non-small-cell lung cancer. Carillio, G., Montanino, A., Costanzo, R., et al.[2018]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06428500

QTX3046 in Patients With KRAS G12D Mutations Phase 1 study to determine the safety and tolerability of QTX3046 as a single agent or in combination with cetuximab.

2. sciencedirect.com sciencedirect.com/science/article/pii/S2405803324002759

KRAS inhibitors: resistance drivers and combinatorial ... In this review, we highlight the progress on defining resistance mechanisms and developing combination treatment strategies to improve patient responses to ...

3. mdanderson.org mdanderson.org/patients-family/diagnosis-treatment/clinical-trials/clinical-trials-index/clinical-trials-detail.ID2024-0550.html

A phase 1 trial evaluating the safety, tolerability, ... A phase 1 trial evaluating the safety, tolerability, pharmacokinetics and efficacy of QTX3046 in patients with advanced solid tumors with KRASG12D mutations.

4. quantatx.com quantatx.com/news/06-27-24/

Phase 1 clinical trial underway evaluating QTX3046 ... Phase 1 clinical trial underway evaluating QTX3046, a novel orally bioavailable and brain-penetrant, non-covalent allosteric ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11853620/

Recent Anti-KRASG12D Therapies: A “Possible Impossibility ... Multiple clinical trials are testing the safety and efficacy of KRASG12D therapy in solid tumors, including for PDAC. A phase I trial of HRS- ...

6. quantatx.com quantatx.com/news/010825/

January 8, 2025 Press Release QTX3046 is a KRASG12D-selective, dual ON/OFF state inhibitor. Both Phase 1 clinical trials are enrolling patients with solid tumors with ...

7. trialx.com trialx.com/clinical-trials/listings/293244/qtx3046-in-patients-with-kras-g12d-mutations/

QTX3046 in Patients With KRAS G12D Mutations Overview. Phase 1 study to determine the safety and tolerability of QTX3046 as a single agent or in combination with cetuximab.

8. synapse.patsnap.com synapse.patsnap.com/drug/5c9b68b3ecc54449a5b67add6107502d

QTX-3046 - Drug Targets, Indications, Patents A Phase 1 Trial Evaluating the Safety, Tolerability, Pharmacokinetics and Efficacy of QTX3046 in Patients with Advanced Solid Tumors with KRAS G12D Mutations.

9. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.TPS3172

A phase 1 trial evaluating the safety, tolerability, PK, and ... QTX3034 is a highly-selective, non-covalent, orally bioavailable, multi-KRAS inhibitor with potent activity across several KRAS variants, particularly G12D.