KQB365 for Cancer

Recruiting at 4 trial locations

Overseen By Kumquat Clinical Development

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Kumquat Biosciences Inc.

Disqualifiers: CNS tumors, Cardiac abnormalities, Lung disease

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

Compensation: Varies

Number of Visits: 9

Duration: 6 weeks

128 Participants Needed

Trial Summary

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 data supports the effectiveness of the drug KQB365 for cancer treatment?

Research on Kahalalide F, a component of KQB365, shows it can kill cancer cells by targeting specific proteins and pathways, like ErbB3 and PI3K-Akt, which are important for cancer cell survival. This suggests that KQB365 might be effective in treating certain cancers by disrupting these pathways. ^{1 2 3 4 5}

Is KQB365 (Cetuximab) generally safe for humans?

The safety of cancer drugs, including KQB365 (Cetuximab), is closely monitored due to frequent adverse reactions. While serious adverse reactions are often reported, continuous monitoring is necessary to ensure safety, as new reactions can emerge over time. ^{6 7 8 9 10}

How does the drug KQB365 work differently from other cancer treatments?

KQB365 may work by inducing the expression of KLF4, a protein that can act as a tumor suppressor in certain cancers, potentially enhancing the effectiveness of existing chemotherapy drugs like paclitaxel and cisplatin. ^{3 11 12 13 14}

What is the purpose of this trial?

The goal of this clinical trial is to learn if KQB365 works to treat advanced solid tumor cancer in adults. It will also learn about the safety of KQB365. The main questions it aims to answer are: * What is the safe dose of KQB365 by itself or in combination with cetuximab? * Does KQB365 alone or in combination with cetuximab decrease the size of the tumor? * What happens to KQB365 in the body? Participants will: * Receive KQB365 infusion weekly alone or in combination with cetuximab * Visit the clinic about 9 times in the first 6 weeks, and then once every week after that.

Eligibility Criteria

This trial is for adults with advanced solid tumors, specifically colorectal cancer with certain KRAS mutations, who can't be cured by surgery or other treatments. They must have measurable disease and organs that work well.

Inclusion Criteria

My colon or rectum cancer has a specific KRAS mutation.

My cancer cannot be removed by surgery or has spread.

My cancer has a KRAS G12C or G12S mutation.

Exclusion Criteria

I have an active brain tumor.

I have heart problems.

I have an ongoing lung condition that affects the tissue and space around the air sacs.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive KQB365 infusion weekly alone or in combination with cetuximab

6 weeks

9 visits (in-person) in the first 6 weeks, then weekly

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Long-term follow-up

Participants are monitored for long-term safety and efficacy outcomes

up to 35 months

Treatment Details

Interventions

• Cetuximab
• KQB365

Trial Overview The study tests KQB365's safety and effectiveness against advanced solid tumor cancers, alone or paired with cetuximab. It seeks the safest dose, whether it shrinks tumors, and how the body processes it.

Participant Groups

Group I: Monotherapy Dose Expansion - RP2D-1 Experimental Treatment 1 Intervention

Drug: KQB365 - Intravenous KQB365

Group II: Monotherapy Dose Expansion - RP2D Experimental Treatment 1 Intervention

Drug: KQB365 - Intravenous KQB365

Group III: Monotherapy Dose Escalation Experimental Treatment 1 Intervention

Drug: KQB365 - Intravenous KQB365

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

Drug: KQB365 - Intravenous KQB365 Drug: - Intravenous cetuximab

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

Drug: KQB365 - Intravenous KQB365 Drug: - Intravenous cetuximab

Group VI: Combo Therapy Dose Escalation Experimental Treatment 2 Interventions

Drug: KQB365 - Intravenous KQB365 Drug: - Intravenous cetuximab

Who Is Running the Clinical Trial?

Kumquat Biosciences Inc.

Lead Sponsor

Trials

3

Recruited

350+

Findings from Research

Kahalalide F (KF) is a potent marine-derived antitumor agent that induces necrosis-like cell death in breast cancer cell lines, rather than apoptosis, as indicated by the absence of typical apoptotic markers after treatment.

The sensitivity of various human tumor cell lines to KF is linked to the levels of ErbB3 (HER3) protein, and KF effectively inhibits the PI3K-Akt signaling pathway, suggesting that targeting these pathways may enhance its therapeutic efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Kahalalide F induces necrosis-like cell death that involves depletion of ErbB3 and inhibition of Akt signaling. Janmaat, ML., Rodriguez, JA., Jimeno, J., et al.[2021]

In a study involving 70 patients with advanced non-small cell lung cancer, the combination of oral CP-547,632 with paclitaxel and carboplatin was generally well-tolerated at doses up to 200 mg daily, although a higher dose of 250 mg caused significant side effects like grade 3 rash and diarrhea.

Despite being well-tolerated, CP-547,632 did not enhance the effectiveness of chemotherapy, as the objective response rates were similar between patients receiving the combination treatment and those receiving chemotherapy alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I/randomized phase II, non-comparative, multicenter, open label trial of CP-547,632 in combination with paclitaxel and carboplatin or paclitaxel and carboplatin alone as first-line treatment for advanced non-small cell lung cancer (NSCLC). Cohen, RB., Langer, CJ., Simon, GR., et al.[2022]

KLF4 is downregulated in ovarian cancer tissues compared to normal tissues, and low levels of KLF4 are associated with more aggressive cancer and poorer survival rates for patients.

Inducing KLF4 expression using a small molecule called APTO-253 enhances the effectiveness of chemotherapy drugs like paclitaxel and cisplatin, suggesting a new therapeutic approach for ovarian cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

KLF4 expression enhances the efficacy of chemotherapy drugs in ovarian cancer cells. Wang, B., Shen, A., Ouyang, X., et al.[2021]

KLF5 is overexpressed in 53% of epithelial ovarian cancer (EOC) samples and is linked to aggressive cancer characteristics, indicating its potential as a therapeutic target.

Knocking down KLF5 in EOC cell lines reduced cell growth, migration, and invasion, and enhanced the effectiveness of cisplatin, suggesting that targeting KLF5 could improve treatment outcomes for patients with EOC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Krupple-Like Factor 5 is a Potential Therapeutic Target and Prognostic Marker in Epithelial Ovarian Cancer. Siraj, AK., Pratheeshkumar, P., Divya, SP., et al.[2021]

APTO-253, a drug tested in a Phase I study with 32 patients suffering from advanced solid tumors, was found to be well tolerated, with fatigue being the most common side effect, occurring in over 10% of participants.

At the recommended Phase 2 dose of 229 mg/m², APTO-253 showed evidence of antitumor activity, achieving stable disease in 24% of patients, indicating potential effectiveness in treating advanced solid tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1 study of APTO-253 HCl, an inducer of KLF4, in patients with advanced or metastatic solid tumors. Cercek, A., Wheler, J., Murray, PE., et al.[2021]

The study evaluated an automated method for detecting serious adverse drug reactions (ADRh) in cancer patients undergoing oral targeted therapy, using data from 129 patients and focusing on hospitalizations within 3 months of treatment initiation.

The detection method achieved a high specificity of 97.8% with restrictive filters, but only a sensitivity of 38.2%, indicating that while it can accurately identify ADRh, it may miss a significant number of cases, suggesting the need for further testing in pharmacovigilance settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Detection of adverse drug reactions: evaluation of an automatic data processing applied in oncology performed in the French Diagnosis Related Groups database. Quillet, A., Colin, O., Bourgeois, N., et al.[2018]

A new tool for clinicians in inpatient oncology units has been developed to prevent adverse events and enhance patient safety, focusing specifically on cancer patients.

The tool includes a catalog of adverse events and a risk map, which helps healthcare providers implement best practices in their daily activities to improve clinical safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improving patient safety in the inpatient setting through risk assessment and mitigation. Reche Navarro, MN.[2016]

A virtual interdisciplinary communication workshop was found to be feasible and acceptable for improving communication among oncology team members, based on feedback from 87 patients and 56 clinicians.

The workshop highlighted areas for improvement in communication practices, suggesting that targeted interventions can enhance patient care and safety in ambulatory oncology settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development and Evaluation of a Data-Driven, Interactive Workshop to Facilitate Communication and Teamwork in Ambulatory Medical Oncology Settings. Blok, AC., Costa, DK., Wright, NC., et al.[2023]

A recent study identified 76 serious adverse drug reactions (ADRs) associated with oncologic drugs, with 50% of these being potentially fatal, highlighting the critical need for ongoing safety monitoring in cancer treatments.

Notably, 49% of the serious ADRs were not included in the initial drug labels, indicating that many risks may only be recognized after broader clinical use, underscoring the importance of spontaneous reporting systems for drug safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse reactions to oncologic drugs: spontaneous reporting and signal detection. Tuccori, M., Montagnani, S., Capogrosso-Sansone, A., et al.[2014]

A quality improvement initiative at the Center for Cancer Care tracked adverse outcomes in 91 patients receiving radiotherapy, revealing that 54.9% experienced treatment-related toxicity and 21.1% died during or shortly after treatment.

The study found that advanced age was linked to poorer overall and disease-free survival, indicating that healthcare providers should pay special attention to elderly patients undergoing radiotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quality improvement program in radiation oncology: understanding patient hospitalizations, treatment breaks, and weight loss in patients receiving radiotherapy. Chowdhry, V., Jangro, P., Goldberg, S., et al.[2019]

KLF4 expression is significantly reduced in gastric cancer tissues compared to normal gastric mucosa, and its loss is associated with poorer survival outcomes, indicating it may serve as an important prognostic marker.

Restoring KLF4 expression in gastric cancer cells inhibited cell growth and completely prevented metastasis in animal models, suggesting that KLF4 plays a critical role in suppressing tumor progression and may be a potential therapeutic target.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Drastic down-regulation of Krüppel-like factor 4 expression is critical in human gastric cancer development and progression. Wei, D., Gong, W., Kanai, M., et al.[2021]

In a study of 239 breast cancer tissues, KLF4 protein expression was found to be significantly lower in cancerous tissues (39.0%) compared to paracancerous tissues (77.5%), indicating a potential role of KLF4 in breast cancer progression.

Transfection of the KLF4 gene into breast cancer MDA-MB-231 cells led to decreased cell proliferation, suggesting that KLF4 may act as a tumor suppressor and could be important in the treatment or understanding of breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Expression of Krüppel-like factor 4 in breast cancer tissues and its effects on the proliferation of breast cancer MDA-MB-231 cells. Song, X., Xing, YM., Wu, W., et al.[2020]

Histone deacetylase inhibitors (HDACi) like SAHA and TSA can effectively reduce the viability of basal-like breast cancer (BLBC) cells by promoting the acetylation and subsequent degradation of the KLF5 transcription factor.

The study reveals a new mechanism where acetylation of KLF5 at lysine 369 decreases its interaction with the deubiquitinase BAP1, leading to increased ubiquitination and degradation of KLF5, which may help in suppressing BLBC tumor growth.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Histone Deacetylase Inhibitors (HDACi) Promote KLF5 Ubiquitination and Degradation in Basal-like Breast Cancer. Kong, Y., Ren, W., Fang, H., et al.[2022]

KLF4 is highly expressed in breast cancer and plays a crucial role in enhancing tumorigenesis by maintaining cancer stem cell characteristics and promoting cell migration and invasion, as shown in studies with breast cancer cell lines MCF-7 and MDA-MB-231.

Knockdown of KLF4 not only reduced the cancer stem cell population and inhibited tumor growth in mouse models but also suppressed cell migration and invasion, indicating that targeting KLF4 could be a promising therapeutic strategy for breast cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Kruppel-like factor 4 (KLF4) is required for maintenance of breast cancer stem cells and for cell migration and invasion. Yu, F., Li, J., Chen, H., et al.[2022]

References

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

Kahalalide F induces necrosis-like cell death that involves depletion of ErbB3 and inhibition of Akt signaling. [2021]

2. Germany pubmed.ncbi.nlm.nih.gov

A phase I/randomized phase II, non-comparative, multicenter, open label trial of CP-547,632 in combination with paclitaxel and carboplatin or paclitaxel and carboplatin alone as first-line treatment for advanced non-small cell lung cancer (NSCLC). [2022]

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

KLF4 expression enhances the efficacy of chemotherapy drugs in ovarian cancer cells. [2021]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Krupple-Like Factor 5 is a Potential Therapeutic Target and Prognostic Marker in Epithelial Ovarian Cancer. [2021]

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

Phase 1 study of APTO-253 HCl, an inducer of KLF4, in patients with advanced or metastatic solid tumors. [2021]

6. England pubmed.ncbi.nlm.nih.gov

Detection of adverse drug reactions: evaluation of an automatic data processing applied in oncology performed in the French Diagnosis Related Groups database. [2018]

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

Improving patient safety in the inpatient setting through risk assessment and mitigation. [2016]

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

Development and Evaluation of a Data-Driven, Interactive Workshop to Facilitate Communication and Teamwork in Ambulatory Medical Oncology Settings. [2023]

9. England pubmed.ncbi.nlm.nih.gov

Adverse reactions to oncologic drugs: spontaneous reporting and signal detection. [2014]

10. England pubmed.ncbi.nlm.nih.gov

Quality improvement program in radiation oncology: understanding patient hospitalizations, treatment breaks, and weight loss in patients receiving radiotherapy. [2019]

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

Drastic down-regulation of Krüppel-like factor 4 expression is critical in human gastric cancer development and progression. [2021]

12. Greece pubmed.ncbi.nlm.nih.gov

Expression of Krüppel-like factor 4 in breast cancer tissues and its effects on the proliferation of breast cancer MDA-MB-231 cells. [2020]

13. Australia pubmed.ncbi.nlm.nih.gov

Histone Deacetylase Inhibitors (HDACi) Promote KLF5 Ubiquitination and Degradation in Basal-like Breast Cancer. [2022]

14. England pubmed.ncbi.nlm.nih.gov

Kruppel-like factor 4 (KLF4) is required for maintenance of breast cancer stem cells and for cell migration and invasion. [2022]