KQB198 + Osimertinib for Advanced Cancer

Recruiting at 46 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

Trial Summary

What is the purpose of this trial?

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. The main questions it aims to answer are: * What is the safe dose of KQB198 by itself or in combination with other anti-cancer drugs? * Does KQB198 alone or in combination with other anti-cancer drugs decrease the size of the tumor? * What happens to KQB198 in the body? Participants will: * Take KQB198 daily, alone or in combination with another anti-cancer drug * Visit the clinic about 8 times in the first 8 weeks, and then once every 4 weeks after that

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.

What safety information is available for the treatment KQB198 + Osimertinib?

Osimertinib, a part of the treatment, has been associated with some side effects like diarrhea, rash, dry skin, nail issues, and fatigue. It may also cause heart-related issues such as QTc prolongation (a heart rhythm condition), atrial fibrillation (irregular heartbeat), and heart failure, especially in older patients. Monitoring for these side effects is important during treatment. ^{1 2 3 4 5}

What makes the drug KQB198 + Osimertinib unique for advanced cancer?

The combination of KQB198 with Osimertinib is unique because it potentially addresses resistance issues seen with Osimertinib alone, particularly in cases where mutations like EGFR cis-C797S cause resistance to treatment. This combination could offer a new approach for patients who have developed resistance to existing therapies. ^{6 7 8 9 10}

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

Group I: Monotherapy Dose Escalation Experimental Treatment 1 Intervention

Group II: Combo Therapy Dose Expansion OBD Experimental Treatment 2 Interventions

Group III: Combo Therapy Dose Expansion - RP2D-1 Experimental Treatment 2 Interventions

Group IV: Combo Therapy Dose Expansion - RP2D Experimental Treatment 2 Interventions

Group V: Combo Therapy Dose Escalation Experimental Treatment 2 Interventions

Who Is Running the Clinical Trial?

Kumquat Biosciences Inc.

Lead Sponsor

Trials

3

Recruited

350+

Findings from Research

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]

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]

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 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]

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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Multiple cardiotoxicities during osimertinib therapy. [2023]

2. England pubmed.ncbi.nlm.nih.gov

A real-world pharmacovigilance study of FDA Adverse Event Reporting System (FAERS) events for osimertinib. [2023]

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

Long QT syndrome after using EGFR-TKIs in older patients with advanced non-small cell lung cancer. [2023]

4. England 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. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Population pharmacokinetics and exposure-response of osimertinib in patients with non-small cell lung cancer. [2022]

6. United States 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. [2021]

7. Korea (South) 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. [2022]

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

Osimertinib in Untreated EGFR-Mutated Advanced Non-Small-Cell Lung Cancer. [2022]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Effectiveness of osimertinib in patients with lung adenocarcinoma in clinical practice - the Expanded Drug Access Program in Poland. [2022]

10. Ireland pubmed.ncbi.nlm.nih.gov

Aplastic anemia in a patient with advanced lung adenocarcinoma during first line osimertinib: A case report and literature review. [2022]