KB707 for Lung Cancer

Recruiting in Palo Alto (17 mi)

+8 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Recruiting

Sponsor: Krystal Biotech, Inc.

Must be taking: Keytruda

Disqualifiers: HIV, Active brain metastases, Autoimmune, others

No Placebo Group

Breakthrough Therapy

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.

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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.

I am 18 years old or older.

Life expectancy >12 weeks

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.

Trial 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

Participant Groups

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.

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.

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

UPMC Hillman Cancer Center Pittsburgh, PA

HonorHealth Research Institute Scottsdale, AZ

Sarah Cannon Research Institute Nashville, TN

IU Simon Comprehensive Cancer Center Indianapolis, IN

More Trial Locations

Who Is Running the Clinical Trial?

Krystal Biotech, Inc. Lead Sponsor

References

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

Risk score for non-small cell lung cancer patients starting checkpoint inhibitor treatment. [2022] Prognosis of metastatic non-small cell lung cancer significantly improved with the availability of checkpoint inhibitors (anti-PD-1/PD-L1). Unfortunately, reliable biomarkers to predict treatment benefit are lacking.

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] This review was implemented to examine the impact of bone metastasis on the prognosis of non-small cell lung cancer patients (NSCLC) treated with immune checkpoint inhibitors (ICIs).

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

The End of Nihilism: Systemic Therapy of Advanced Non-Small Cell Lung Cancer. [2018] Lung cancer is the leading cause of cancer death in the United States and many other parts of the world. Non-small cell lung cancer (NSCLC) comprises 85-90% of lung cancers. Historically, the expected survival of patients with advanced disease has been estimated in months. In recent years, however, lung cancer has come to be seen as a treatable disease with multiple therapeutic options. Enormous advances in the understanding of its pathways and mechanisms have enabled personalized therapy in NSCLC. The evolving approach to therapy focuses on genomic profiling of the tumors to find molecular targets and develop specific agents for individualized therapy. In addition, maintenance therapy has emerged as a valid approach, and the choice of chemotherapy now varies by histology. Most recently, immunotherapy with checkpoint inhibitors has shown promising results, with impressive durations of response and a tolerable toxicity profile. Together, these discoveries have improved overall survival substantially in patient populations that have access to these advancements. We review the clinical data surrounding these impressive improvements.

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

Perioperative Systemic Therapy for Resectable Non-Small Cell Lung Cancer. [2022] Despite remarkable treatment advancements in patients with advanced non-small cell lung cancer (NSCLC), recurrence rates for those with resectable, early-stage disease remains high. Immune checkpoint inhibitors and targeted therapies are 2 promising treatment modalities that may improve survival outcomes for patients with resected NSCLC when moved from the advanced stage to the curable setting. There are many clinical studies that have evaluated or are currently evaluating immunotherapy or targeted therapy in the perioperative setting, and recent trials such as CheckMate 816, ADAURA, and IMpower010 have led to new approvals and demonstrated the promise of this approach. This review discusses recent and ongoing neoadjuvant and adjuvant systemic therapy trials in NSCLC, and where the field may be going in the near future.

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] Currently, survival benefit of immunotherapy in advanced non-small cell lung cancer (NSCLC) with EGFR exon 20 insertions (ex20ins) is controversial, though it generally indicates poor response and activity. Compared with standard chemotherapy in combination with bevacizumab, first-line chemotherapy plus immune checkpoint inhibitor (ICI) in advanced NSCLC with EGFR ex20ins remains elusive and lacks real-world evidence.