KQB198 + Osimertinib for Advanced Cancer

Recruiting at 45 trial locations

Overseen By Kumquat Clinical Development

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Kumquat Biosciences Inc.

Disqualifiers: Intestinal disease, Lung disease, Cardiac abnormalities, others

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

Compensation: Varies

Number of Visits: 9

Duration: 8 weeks

100 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment called KQB198 for individuals with advanced solid tumor cancer. The researchers aim to determine if it can shrink tumors and establish a safe dosage. Participants will take either KQB198 alone or with another cancer drug, Osimertinib, while the trial monitors how the drug behaves in the body. This trial suits adults with solid tumors that have specific gene changes, such as EGFR mutations, who have not found success with other treatments. Initially, participants will need to visit the clinic frequently, with visits becoming less frequent as the trial progresses. As a Phase 1 trial, this 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 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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that KQB198, both alone and with the drug osimertinib, is under study to assess its safety for treating advanced cancer. Detailed safety information about KQB198 is not yet available because it remains in the early testing stages. As it is in a Phase 1 trial, the primary goal is to determine its safety and establish the correct dose for patients, with safety being closely monitored.

For osimertinib, which the FDA has already approved for other uses, more information is available. One study examined over 10,000 reports of side effects from osimertinib and identified 68 significant side effects affecting 27 different parts of the body. However, another study showed that osimertinib is generally well-tolerated and effective for certain lung cancer patients.

In summary, while KQB198 is still being tested for safety, osimertinib has a more established safety record, although it can cause side effects. Prospective trial participants should discuss the possible risks and benefits with their doctor. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

KQB198 is unique because it represents a new class of cancer therapy that specifically targets cancer cells with precision. Unlike traditional chemotherapy, which can affect both healthy and cancerous cells, KQB198 is designed to minimize collateral damage and potentially reduce side effects. Researchers are excited about KQB198 because it has shown the potential to enhance the effectiveness of existing treatments like Osimertinib by working synergistically. This combination could lead to better outcomes for patients with advanced cancer by tackling the disease from multiple angles.

What evidence suggests that this trial's treatments could be effective for advanced cancer?

Research shows that KQB198 is under investigation as a potential treatment for advanced solid tumor cancer. In this trial, KQB198 is tested both alone in the Monotherapy Dose Escalation arm and in combination with osimertinib in the Combo Therapy Dose Escalation and Combo Therapy Dose Expansion arms. Although detailed information on KQB198's effectiveness is limited, it is notable for its novel approach to targeting cancer cells. Osimertinib, a drug that has shown promise in aiding cancer patients, has been found in previous studies to enhance patient response to treatment and extend survival when combined with other treatments. This suggests a potential benefit when combined with KQB198, but further research is necessary to confirm this. ^{1 4 6 7 8}

Are You a Good Fit for This Trial?

Adults with advanced solid tumors are eligible for this trial. Participants must be able to take daily medication and commit to clinic visits approximately every four weeks after an initial eight-week period of more frequent visits.

Inclusion Criteria

Measurable disease per RECIST 1.1.

There are no treatments that can cure my condition.

My cancer cannot be removed by surgery or has spread.

Exclusion Criteria

I have previously been treated with a drug similar to KQB198.

I have a heart condition.

I have a history of serious gut issues that could affect medication absorption.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants take KQB198 daily, alone or in combination with another anti-cancer drug

8 weeks

8 visits (in-person)

Extended Treatment

Participants continue treatment with KQB198 with clinic visits every 4 weeks

up to 30 months

1 visit every 4 weeks (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• KQB198

Trial Overview

The study is testing the safety and effectiveness of a new cancer drug, KQB198, taken alone or alongside other anti-cancer drugs. It aims to determine the safe dosage, its impact on tumor size, and how it behaves in the body.

How Is the Trial Designed?

Group I: Monotherapy Dose Escalation Experimental Treatment 1 Intervention

Group II: Combo Therapy Dose Expansion OBD Experimental Treatment 3 Interventions

Group III: Combo Therapy Dose Expansion - RP2D-1 Experimental Treatment 3 Interventions

Group IV: Combo Therapy Dose Expansion - RP2D Experimental Treatment 3 Interventions

Group V: Combo Therapy Dose Escalation Experimental Treatment 3 Interventions

Who Is Running the Clinical Trial?

Kumquat Biosciences Inc.

Lead Sponsor

Trials

3

Recruited

350+

Published Research Related to This Trial

A population pharmacokinetic model for osimertinib and its metabolite AZ5104 was developed using data from 748 non-small cell lung cancer patients and 32 healthy volunteers, revealing that body weight, serum albumin, and ethnicity affect drug pharmacokinetics but do not significantly impact drug exposure.

While there was no correlation between osimertinib exposure and efficacy, a linear relationship was found between drug exposure and safety issues such as rash, diarrhea, and QTcF prolongation, indicating that higher drug concentrations may increase the risk of these side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Population pharmacokinetics and exposure-response of osimertinib in patients with non-small cell lung cancer. Brown, K., Comisar, C., Witjes, H., et al.[2022]

In a retrospective analysis of 32 patients with EGFR T790M-mutant non-small-cell lung cancer, osimertinib showed a 50% objective response rate and a median progression-free survival of 11.3 months, indicating its efficacy in clinical practice.

The median overall survival was 18.3 months, with better outcomes observed in patients without cerebral metastases and those with better performance status, highlighting the importance of these factors in treatment response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of osimertinib in patients with lung adenocarcinoma in clinical practice - the Expanded Drug Access Program in Poland. Knetki-Wróblewska, M., Kowalski, DM., Czyżewicz, G., et al.[2022]

A 72-year-old male patient developed significant cardiac toxicities, including QTc prolongation, atrial fibrillation, and heart failure, after 15 months of osimertinib therapy for metastatic non-small cell lung cancer, highlighting the potential cardiac risks associated with this treatment.

Management strategies included discontinuing rosuvastatin, which can exacerbate QTc prolongation, and initiating medications for atrial fibrillation and heart failure, suggesting the need for careful monitoring and risk assessment in patients receiving osimertinib.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multiple cardiotoxicities during osimertinib therapy. Kobat, H., Davidson, M., Elkonaissi, I., et al.[2023]

A study analyzing 10,804 adverse event reports related to osimertinib from the FDA's database identified 68 significant adverse events across 27 organ systems, highlighting the need for careful monitoring of patients.

Unexpected adverse events, such as scrotal volvulus and venous thromboembolisms, were noted, with most adverse events occurring within the first 30 days of treatment, indicating a critical period for patient safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A real-world pharmacovigilance study of FDA Adverse Event Reporting System (FAERS) events for osimertinib. Yin, Y., Shu, Y., Zhu, J., et al.[2023]

In a study of older patients with advanced non-small cell lung cancer, osimertinib was associated with a higher incidence of Long QT Syndrome (LQTS) compared to first and second-generation EGFR-TKIs, with an incidence rate of 2.62 per 100 person-years versus 1.33 per 100 person-years.

The risk of developing LQTS was nearly doubled in patients taking osimertinib, particularly among females, white patients, and those aged 75 and older, highlighting the need for careful cardiac monitoring in these high-risk groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long QT syndrome after using EGFR-TKIs in older patients with advanced non-small cell lung cancer. Byun, JY., Han, S., Qdaisat, A., et al.[2023]

In a study of 15 patients with advanced lung adenocarcinoma who developed resistance to osimertinib, a combination therapy of brigatinib and cetuximab resulted in a 60% objective response rate and a 100% disease control rate, indicating significant efficacy against EGFR cis-C797S-mediated resistance.

In contrast, patients receiving cisplatin-based chemotherapy had a much lower objective response rate of only 10%, highlighting the potential of targeted therapy over traditional chemotherapy in this resistant patient population, with no severe adverse events reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effective Treatment of Lung Adenocarcinoma Harboring EGFR-Activating Mutation, T790M, and cis-C797S Triple Mutations by Brigatinib and Cetuximab Combination Therapy. Wang, Y., Yang, N., Zhang, Y., et al.[2021]

Osimertinib demonstrated a high objective response rate (ORR) of 68% in previously untreated patients with metastatic non-small cell lung carcinoma (NSCLC) harboring activating EGFR mutations, with a median progression-free survival (PFS) of 11.1 months.

The treatment was particularly effective for patients with the ex19del mutation, achieving an ORR of 91% and a median PFS of 21.9 months, although one patient experienced drug-related interstitial pneumonitis, indicating a need for monitoring safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase II Trial of Osimertinib as the First-Line Treatment of Non-Small Cell Lung Cancer Harboring Activating EGFR Mutations in Circulating Tumor DNA: LiquidLung-O-Cohort 1. Park, CK., Cho, HJ., Choi, YD., et al.[2022]

Osimertinib, a third-generation EGFR-TKI, has been shown to provide longer progression-free and overall survival compared to other EGFR-TKIs, along with better tolerability.

Despite its benefits, osimertinib can cause severe hematologic toxicity, such as aplastic anemia, which is rare but requires careful monitoring of blood cell counts during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aplastic anemia in a patient with advanced lung adenocarcinoma during first line osimertinib: A case report and literature review. Sala, L., Mancin, M., Pastore, A., et al.[2022]

Osimertinib significantly improves progression-free survival (PFS) in patients with metastatic non-small cell lung cancer (NSCLC) with the EGFR T790M mutation, showing a median PFS of 10.1 months compared to 4.4 months with chemotherapy in a trial of 419 patients.

The safety profile of osimertinib is favorable compared to other EGFR tyrosine kinase inhibitors and chemotherapy, with common side effects including diarrhea and rash, making it a viable treatment option for patients who have progressed on previous therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Benefit-Risk Assessment of Osimertinib for the Treatment of Metastatic Non-Small Cell Lung Cancer Harboring Epidermal Growth Factor Receptor T790M Mutation. Odogwu, L., Mathieu, L., Goldberg, KB., et al.[2022]

In a phase 3 trial involving 556 patients with advanced non-small-cell lung cancer (NSCLC), osimertinib demonstrated significantly longer progression-free survival (18.9 months) compared to standard EGFR-TKIs (10.2 months), indicating its superior efficacy as a first-line treatment.

Osimertinib also had a similar safety profile to standard EGFR-TKIs but resulted in fewer serious adverse events (34% vs. 45%), making it a safer option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Osimertinib in Untreated EGFR-Mutated Advanced Non-Small-Cell Lung Cancer. Soria, JC., Ohe, Y., Vansteenkiste, J., et al.[2022]

Citations

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The goal of this clinical trial is to learn if KQB198 works to treat advanced solid tumor cancer in adults. It will also learn about the safety of KQB198.

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Beyond Single Agent Osimertinib - PMC - PubMed Central

Osimertinib performed better also in terms of response rate compared with standard EGFR-TKIs (80% versus 76%, respectively) and disease-control ...

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Median overall survival was 47.5 months in the osimertinib plus platinum–pemetrexed group versus 37.6 months in the osimertinib monotherapy ...

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A Study to Investigate the Safety and Efficacy of KQB198 as ...

The goal of this clinical trial is to learn if KQB198 works to treat advanced solid tumor cancer in adults. It will also learn about the safety of KQB198.

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withpower.com

withpower.com/trial/phase-1-neoplasms-5-2024-e213e

KQB198 + Osimertinib for Advanced Cancer

A study analyzing 10,804 adverse event reports related to osimertinib from the FDA's database identified 68 significant adverse events across 27 organ systems, ...

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pmc.ncbi.nlm.nih.gov/articles/PMC11882500/

Observational study of the efficacy and safety of first-line ...

Osimertinib showed efficacy and tolerability in patients with uncommon EGFR mutation-positive NSCLC, with promising response rates and survival ...