KB707 for Lung Cancer

Recruiting at 8 trial locations

Overseen By Brittani Agostini, RN, CCRC

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Krystal Biotech, Inc.

Must be taking: Keytruda

Disqualifiers: HIV, Active brain metastases, Autoimmune, others

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

Compensation: Varies

Number of Visits: 5

200 Participants Needed

Trial Summary

What is the purpose of this trial?

The Sponsor is developing KB707, a replication-defective, non-integrating herpes simplex virus type 1 (HSV-1)-derived vector that is designed to stimulate an anti-tumor immune response through the production of cytokines delivered to the airways of people with advanced solid tumor malignancies affecting the lungs via nebulization. This Phase 1/2, open-label, multicenter, dose escalation and expansion study is designed to evaluate the safety and tolerability of KB707 in adults with with advanced solid tumor malignancies affecting the lungs who have progressed on standard of care therapy, cannot tolerate standard of care therapy, or refused standard of care therapy, as well as the safety, tolerability, preliminary efficacy, and immunologic effect of KB707 administered in combination with Keytruda, with or without chemotherapy, to subjects with advanced NSCLC. The study will include a dose escalation portion for single agent KB707 using a standard 3+3 design followed by a dose expansion portion to further evaluate single agent KB707 at a dose determined by preliminary data in the dose escalation phase. Subjects in the dose escalation (Cohorts 1 and 2) and dose expansion (Cohort 4) will receive KB707 via nebulization weekly for three weeks, then every three weeks. The dose escalation portion of the study has now closed, and the Cohort 2 dose was selected for evaluation in dose expansion. Dose expansion Cohorts 5 and 6 will evaluate subjects with advanced non-small cell lung cancer (NSCLC). Subjects in Cohorts 5 and 6 will receive inhaled KB707 per treatment day once every 2 weeks (q2w), delivered in combination with Keytruda (once every 6 weeks). All subjects will be treated until tumor progression, death, unacceptable toxicity, symptomatic deterioration, achievement of maximal response, subject choice, Investigator decision to discontinue treatment, or the Sponsor determines to terminate the study.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, since the study involves treatment with KB707 and Keytruda, it's best to discuss your current medications with the study team to ensure there are no interactions.

What data supports the effectiveness of the drug KB707 for lung cancer?

Research shows that immunotherapy, which includes drugs like checkpoint inhibitors, has improved survival rates in non-small cell lung cancer (NSCLC) by targeting specific pathways in the cancer cells. These treatments have shown promising results with longer response durations and manageable side effects. ^{1 2 3 4 5}

Research Team

David Chien, MD

Principal Investigator

Senior Vice President of Clinical Development

Eligibility Criteria

This trial is for adults with advanced lung-related cancers who have either not responded to, cannot handle, or chose not to undergo standard treatments. It's open to those with a variety of solid tumors in the lungs, including different types of lung cancer and other malignancies like osteosarcoma and liver cancer.

Inclusion Criteria

My lung cancer has worsened despite treatment, or I can't undergo standard treatments.

Life expectancy >12 weeks

I am fully active or can carry out light work.

Exclusion Criteria

The subject is pregnant, nursing, or plans to become pregnant during study treatment and through three months after the last dose of KB707

I have a known history of HIV.

I haven't had cancer treatment or used experimental drugs/devices within the last 21 days or 5 half-lives.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Subjects receive single-agent KB707 via nebulization weekly for three weeks, then every three weeks in a standard 3+3 design

9 weeks

Weekly visits for 3 weeks, then every 3 weeks

Dose Expansion

Subjects receive inhaled KB707 in combination with Keytruda every 2 weeks, with Keytruda administered every 6 weeks

Until tumor progression or other criteria are met

Every 2 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• KB707

Trial Overview KB707 is being tested; it's a new type of therapy using a modified virus designed to boost the body’s immune response against lung tumors. Participants will inhale this treatment through nebulization. The study has two parts: first finding the right dose and then giving that dose to more people to see how well it works.

Participant Groups

Group I: Dose Expansion of KB707 Administered in Combination with Keytruda and Chemotherapy Experimental Treatment 3 Interventions

Dose expansion cohort: KB707 administered in combination with Keytruda and chemotherapy in approximately 60 subjects with NSCLC.

Group II: Dose Expansion of KB707 Administered in Combination with Keytruda Experimental Treatment 2 Interventions

Dose expansion cohort: KB707 administered in combination with Keytruda in approximately 60 subjects with NSCLC.

Group III: Dose Escalation of KB707 Administered via Nebulization Experimental Treatment 1 Intervention

Dose escalation of single-agent KB707 in 3 cohorts in a standard 3+3 design.

Who Is Running the Clinical Trial?

Krystal Biotech, Inc.

Lead Sponsor

Trials

15

Recruited

770+

Findings from Research

In a study of 56 non-small cell lung cancer patients treated with checkpoint inhibitors, half achieved disease control, highlighting the potential efficacy of these treatments.

A risk score based on four key inflammation-related parameters can effectively stratify patients into different risk groups, predicting overall and progression-free survival outcomes, which may help guide treatment decisions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk score for non-small cell lung cancer patients starting checkpoint inhibitor treatment. Diem, S., Fässler, M., Hasan Ali, O., et al.[2022]

Bone metastasis in non-small cell lung cancer (NSCLC) patients treated with immune checkpoint inhibitors (ICIs) is linked to significantly poorer overall survival, with a hazard ratio of 1.55 based on a combined analysis of 10 studies involving multiple patients.

However, bone metastasis does not appear to negatively affect progression-free survival in these patients, indicating that while overall survival is compromised, the time until disease progression may remain unaffected.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of bone metastasis on the prognosis of non-small cell lung cancer patients treated with immune checkpoint inhibitors: a systematic review and meta-analysis. Liu, L., Shi, Z., Qiu, X.[2023]

Recent advancements in the understanding of non-small cell lung cancer (NSCLC) have transformed it into a treatable disease, allowing for personalized therapy based on genomic profiling of tumors.

Immunotherapy using checkpoint inhibitors has shown promising results in NSCLC, providing impressive durations of response and a tolerable toxicity profile, significantly improving overall survival rates for patients with access to these treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The End of Nihilism: Systemic Therapy of Advanced Non-Small Cell Lung Cancer. Ernani, V., Steuer, CE., Jahanzeb, M.[2018]

Recent advancements in treatment for early-stage non-small cell lung cancer (NSCLC) using immune checkpoint inhibitors and targeted therapies show promise in improving survival rates, especially after surgical resection.

Clinical trials like CheckMate 816, ADAURA, and IMpower010 have led to new treatment approvals and highlight the potential of using these therapies in the perioperative setting to reduce recurrence rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Perioperative Systemic Therapy for Resectable Non-Small Cell Lung Cancer. Muthusamy, B., Patil, PD., Pennell, NA.[2022]

In a study of 122 patients with advanced non-small cell lung cancer (NSCLC) and EGFR exon 20 insertions, first-line chemotherapy combined with angiogenesis inhibitors showed a significantly better objective response rate (38.1% vs. 18.2%) and longer progression-free survival (7.73 months vs. 5.93 months) compared to chemotherapy alone.

The combination of chemotherapy with immune checkpoint inhibitors did not provide a survival benefit over chemotherapy alone, suggesting that intrinsic resistance mechanisms, possibly linked to the activation of the PI3K/AKT signaling pathway, may limit the effectiveness of immunotherapy in this patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-line immunotherapy or angiogenesis inhibitor combined with chemotherapy for advanced non-small cell lung cancer with EGFR exon 20 insertions: Real-world evidence from China. Yang, G., Yang, Y., Liu, R., et al.[2023]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Risk score for non-small cell lung cancer patients starting checkpoint inhibitor treatment. [2022]

2. Italy pubmed.ncbi.nlm.nih.gov

Impact of bone metastasis on the prognosis of non-small cell lung cancer patients treated with immune checkpoint inhibitors: a systematic review and meta-analysis. [2023]

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

The End of Nihilism: Systemic Therapy of Advanced Non-Small Cell Lung Cancer. [2018]

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

Perioperative Systemic Therapy for Resectable Non-Small Cell Lung Cancer. [2022]

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

First-line immunotherapy or angiogenesis inhibitor combined with chemotherapy for advanced non-small cell lung cancer with EGFR exon 20 insertions: Real-world evidence from China. [2023]