QTX3034 + Cetuximab for Solid Tumors

Recruiting at 15 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 metastases, Cardiovascular disease, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: up to 21 days for initial dose-limiting toxicity assessment, followed by up to 2 years for treatment

250 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a new drug called QTX3034, either by itself or with an existing cancer treatment called cetuximab. Cetuximab has been used in various cancer treatments, though its benefits have been mixed. It aims to find out if QTX3034 is safe and can help stop cancer cells from growing. The trial likely involves patients whose cancers have not responded to other treatments.

Do I need to stop my current medications to join the trial?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the drug QTX3034 + Cetuximab for solid tumors?

Cetuximab, one of the components of the treatment, has been shown to be effective in treating certain types of cancer, such as colorectal cancer and head and neck cancer, by targeting the epidermal growth factor receptor (EGFR). It has also shown some benefits in non-small-cell lung cancer, particularly in patients with high EGFR expression. ^{1 2 3 4 5}

What safety information is available for QTX3034 + Cetuximab in humans?

Cetuximab has been studied in humans and is generally safe, but it can cause skin issues, diarrhea, and fatigue. Rarely, it may lead to serious lung problems, so it's important for doctors to monitor patients closely. ^{3 6 7 8 9}

What makes the drug QTX3034 + Cetuximab unique for treating solid tumors?

QTX3034 + Cetuximab is unique because it combines a new treatment, QTX3034, with Cetuximab, a drug that targets the epidermal growth factor receptor (EGFR) and has been used in other cancers like colorectal cancer. This combination may offer a novel approach to treating solid tumors by potentially enhancing the effectiveness of EGFR inhibition. ^{2 3 4 5 9}

Eligibility Criteria

This trial is for adults with advanced solid tumors that have a specific KRAS G12D mutation, confirmed by certified testing. Participants must have tried at least one systemic therapy before and should be in good physical condition (ECOG status 0 or 1). They need to have measurable disease as defined by RECIST criteria and their organs must function well.

Inclusion Criteria

I am fully active or can carry out light work.

My cancer is advanced or has spread, and tests show a KRAS G12D mutation.

For Parts 2 and 3: Measurable disease per RECIST 1.1

Exclusion Criteria

I have a serious heart condition.

I have active brain tumors or cancer in the lining of my brain.

I have had another type of cancer in the last 2 years.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive QTX3034 as monotherapy or in combination with cetuximab in dose-escalation and dose-expansion phases

up to 21 days for initial dose-limiting toxicity assessment, followed by up to 2 years for treatment

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of treatment-emergent adverse events and duration of response

up to 2 years

Treatment Details

Interventions

• QTX3034

Trial Overview The study is evaluating the safety of QTX3034 alone or when used together with cetuximab. It's an early-stage (Phase 1) trial aimed at understanding how patients tolerate these treatments and determining appropriate dosages.

Participant Groups

Group I: Part 3: QTX3034 combination with cetuximab dose-expansion Experimental Treatment 2 Interventions

QTX3034 will be administered at protocol defined dose in combination with cetuximab based on cohort assignment

Group II: Part 2: QTX3034 monotherapy dose-expansion Experimental Treatment 1 Intervention

QTX3034 will be administered at protocol defined dose in combination with cetuximab based on cohort assignment

Group III: Part 1b: QTX3034 combination with cetuximab dose-escalation Experimental Treatment 2 Interventions

QTX3034 will be administered at protocol defined dose in combination with cetuximab based on cohort assignment

Group IV: Part 1a: QTX3034 monotherapy dose-escalation Experimental Treatment 1 Intervention

QTX3034 will be administered at protocol defined dose based on cohort assignment

Who Is Running the Clinical Trial?

Quanta Therapeutics

Lead Sponsor

Trials

3

Recruited

730+

Findings from Research

Cetuximab (CTX) is an effective monoclonal antibody for treating head and neck and colorectal cancers, and measuring its trough levels in plasma can help personalize treatment to improve patient outcomes.

A new high-throughput method using liquid chromatography-high resolution mass spectrometry (LC-HRMS) was developed to accurately measure CTX levels in patients, demonstrating good precision and paving the way for better clinical monitoring of cancer treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Determination of Cetuximab in Plasma by Liquid Chromatography-High-Resolution Mass Spectrometry Orbitrap With a Stable Labeled 13C,15N-Cetuximab Internal Standard. Millet, A., Lebert, D., Picard, G., et al.[2020]

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]

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]

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]

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 monotherapy is a feasible treatment option for patients with metastatic colorectal cancer (MCRC) who are intolerant to irinotecan, with no severe adverse events reported in the study of 22 patients.

The efficacy of cetuximab was modest, with a response rate of only 9.1% and median overall survival of 3.5 months, indicating a need for more effective therapies for this patient group, especially since most had wild-type KRAS tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Retrospective analysis of cetuximab monotherapy for patients with irinotecan-intolerant metastatic colorectal cancer. Mizota, A., Shitara, K., Kondo, C., et al.[2021]

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, an EGFR inhibitor, is effective in treating RAS wild type metastatic colorectal cancer but often causes significant skin toxicities, such as acneiform rash, affecting patient quality of life.

In a case study of a 60-year-old male patient, topical aloe vera extract was found to significantly reduce cetuximab-related acneiform rash, suggesting it may be a safe and effective alternative treatment for managing this common side effect.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Topical aloe vera for the treatment of cetuximab-related acneiform rash in colorectal cancer: A case report. Gürbüz, M., Akkuş, E., Utkan, G.[2021]

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]

References

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

Determination of Cetuximab in Plasma by Liquid Chromatography-High-Resolution Mass Spectrometry Orbitrap With a Stable Labeled 13C,15N-Cetuximab Internal Standard. [2020]

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

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

3. England pubmed.ncbi.nlm.nih.gov

Cetuximab in non-small-cell lung cancer. [2018]

4. England pubmed.ncbi.nlm.nih.gov

Impact of cetuximab in current treatment of metastatic colorectal cancer. [2018]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Two cases of acneiform eruption induced by inhibitor of epidermal growth factor receptor. [2018]

6. Japan pubmed.ncbi.nlm.nih.gov

Retrospective analysis of cetuximab monotherapy for patients with irinotecan-intolerant metastatic colorectal cancer. [2021]

7. France pubmed.ncbi.nlm.nih.gov

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

8. England pubmed.ncbi.nlm.nih.gov

Topical aloe vera for the treatment of cetuximab-related acneiform rash in colorectal cancer: A case report. [2021]

9. Germany pubmed.ncbi.nlm.nih.gov

Cetuximab: appraisal of a novel drug against colorectal cancer. [2019]