KB707 for Lung Cancer

(KYANITE-1 Trial)

Recruiting at 10 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

250 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called KB707, designed to help people with advanced lung cancers. KB707 is a special type of virus that doesn't spread but boosts the immune response directly in the lungs to fight tumors. The trial evaluates its safety and effectiveness, whether used alone or with other treatments like Keytruda or chemotherapy. People with lung cancer that didn’t respond to standard treatments, or who couldn’t or chose not to have those treatments, might be suitable candidates. Participants will inhale the treatment, and the study will continue until their cancer progresses or other conditions are met. 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 innovative therapy.

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.

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

Research shows that inhaled KB707 is generally safe and well tolerated. In earlier studies, most side effects were mild and temporary, often classified as Grade 1 or 2. Even the highest dose tested was safe, as it did not exceed tolerable levels for participants.

When combined with other treatments like Keytruda or docetaxel, studies found these combinations were also well tolerated. For example, Keytruda has been safely used in many patients, and past research demonstrated that combining it with docetaxel was well tolerated.

Overall, evidence suggests that KB707, whether used alone or with other treatments, is safe for people based on these studies. However, each person's experience may differ, and safety is continuously monitored in ongoing trials. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for non-small cell lung cancer (NSCLC), such as chemotherapy, targeted therapy, and immunotherapy, KB707 offers a unique approach. KB707 is exciting because it can be used both as a standalone treatment and in combination with existing therapies like docetaxel and Keytruda. This flexibility allows researchers to explore different treatment combinations, potentially enhancing the effectiveness of current options. Additionally, the potential of KB707 to work synergistically with other drugs could lead to improved outcomes for patients with advanced lung cancer.

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

Research shows that KB707 alone had a 36% success rate in patients with advanced non-small cell lung cancer (NSCLC), with more than a third of patients experiencing tumor shrinkage or halted growth. In this trial, some participants will receive KB707 as monotherapy, while others will receive it combined with Keytruda, an immunotherapy drug. Previous studies also showed a 36% success rate for Keytruda, indicating similar effectiveness. Early evidence suggests this combination may enhance the immune system's ability to fight cancer. Additionally, KB707 will be tested with docetaxel, a chemotherapy drug, where past research found it well tolerated and promising. These findings suggest that KB707, whether used alone or with other treatments, may offer hope for lung cancer patients. ^{3 5 6 7 8}

Who Is on the Research Team?

David Chien, MD

Principal Investigator

Senior Vice President of Clinical Development

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

Group I: Experimental: Cohort 7 Experimental Treatment 2 Interventions

Dose expansion cohort: KB707 administered in combination with docetaxel in approximately 50 subjects with NSCLC.

Group II: Cohorts 1 through 4 Experimental Treatment 1 Intervention

Dose escalation and expansion cohorts: KB707 monotherapy in subjects with solid tumor malignancies affecting the lungs.

Group III: Cohort 6 Experimental Treatment 3 Interventions

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

Group IV: Cohort 5 Experimental Treatment 2 Interventions

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

Who Is Running the Clinical Trial?

Krystal Biotech, Inc.

Lead Sponsor

Trials

15

Recruited

770+

Published Research Related to This Trial

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]

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]

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]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/32271354/

Efficacy and Safety of Pembrolizumab Plus Docetaxel vs ... In this phase 2 study, the combination of pembrolizumab plus docetaxel was well tolerated and substantially improved ORR and PFS in patients with advanced ...

2. onclive.com onclive.com/view/development-program-for-kb707-will-prioritize-inhaled-formulation-for-nsclc

Development Program for KB707 Will Prioritize Inhaled ... With extended follow-up, the ORR was 36%, with 4 patients achieving a PR. Regarding safety, any-grade treatment-related adverse effects (TRAEs) ...

3. ir.krystalbio.com ir.krystalbio.com/news-releases/news-release-details/krystal-biotech-announces-update-development-plans-oncology

Krystal Biotech Announces Update on Development Plans ... Evidence supporting the prioritization of inhaled KB707, including monotherapy activity and durable responses in heavily pre-treated patients with NSCLC, was ...

4. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2024-03666

A Study Assessing KB707 for the Treatment of Advanced ... 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 ...

5. clin.larvol.com clin.larvol.com/trial-detail/NCT06228326

A Study Assessing KB707 for the Treatment of Advanced ... | "A total of 37 patients were enrolled and received at least one dose of inhaled KB707, including 17 patients with a diagnosis of advanced NSCLC....As of the ...

6. ir.krystalbio.com ir.krystalbio.com/news-releases/news-release-details/krystal-biotech-announces-early-evidence-monotherapy-activity

Krystal Biotech Announces Early Evidence of Monotherapy ... Preliminary clinical data in post-anti-PD-1 NSCLC patients demonstrated a 27% ORR and 73% DCR in monotherapy trial.

7. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.2575

Inhaled KB707, a novel HSV-based immunotherapy, as ... KB707 administered by inhalation was safe and well tolerated. The MTD was not reached, and the monotherapy recommended Phase 2 dose is 10 9 PFU.

8. clinicaltrial.be clinicaltrial.be/en/details/423321?per_page=20&only_recruiting=0&only_eligible=0&only_active=0

A Study Assessing KB707 for the Treatment of Advanced ... This is a Phase 1/2, open-label, multicenter, dose escalation and expansion study designed to evaluate the safety, tolerability, preliminary ...