LNS8801 + Pembrolizumab for Cancer

Recruiting in Palo Alto (17 mi)

+9 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Recruiting

Sponsor: Linnaeus Therapeutics, Inc.

Must not be taking: Estrogen-based contraceptives

Disqualifiers: Thyroid cancer, Gall bladder cancer, others

No Placebo Group

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

This trial tests a new drug called LNS8801 alone and with another drug, pembrolizumab, in patients with advanced cancers who haven't responded to other treatments or had severe side effects. LNS8801 targets and kills cancer cells directly, while pembrolizumab helps the immune system fight cancer.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, certain medications like strong inhibitors or inducers of specific enzymes, proton pump inhibitors, and estrogen treatments are not allowed. It's best to discuss your current medications with the study team to see if any adjustments are needed.

What data supports the effectiveness of the drug pembrolizumab in treating cancer?

Pembrolizumab has been shown to be effective in treating various cancers, including non-small cell lung cancer and melanoma, by improving survival rates and reducing tumor size. It works by helping the immune system attack cancer cells more effectively. ^{1 2 3 4 5}

Is the combination of LNS8801 and Pembrolizumab safe for humans?

Pembrolizumab, also known as Keytruda, has been used in various cancer treatments and is generally considered safe, but it can cause side effects like fatigue, cough, nausea, and more serious immune-related issues like pneumonitis (lung inflammation) and thyroid problems. While specific safety data for LNS8801 combined with Pembrolizumab is not provided, Pembrolizumab alone has been studied extensively and is approved for use in several cancers. ^{1 4 5 6 7}

What makes the drug LNS8801 + Pembrolizumab unique for cancer treatment?

This treatment combines LNS8801 with Pembrolizumab, a PD-1 inhibitor that helps the immune system attack cancer cells. Pembrolizumab is already used for various cancers, but the combination with LNS8801 may offer a new approach to enhance its effectiveness. ^{1 3 5 8 9}

Research Team

Tina Garyantes, PhD

Principal Investigator

Linnaeus Therapeutics, Inc.

Eligibility Criteria

Adults with advanced solid tumors, including specific types of lung and skin cancer, who have measurable disease and are in good physical condition. They must be able to swallow pills, not have certain infections or recent major surgeries, and agree to use effective contraception. Some cohorts require prior treatment history specifics.

Inclusion Criteria

I agree to a biopsy if my tumor can be safely accessed.

I am not currently breastfeeding.

I have pancreatic, gastric, NSCLC, or colorectal cancer.

Exclusion Criteria

I have an immune system disorder or have been on strong immune-weakening medication recently.

I haven't had cancer treatment in the last 4-6 weeks, except for specific immunotherapies.

I have side effects from cancer treatment that haven't fully gone away, except for hair loss.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Dose Escalation

Participants receive LNS8801 in a 3+3 dose escalation design to determine the MTD/RP2D

21-day cycles

Regular visits for dose escalation monitoring

Dose Expansion

Expansion cohorts to further explore PK and PD of LNS8801 alone and in combination with pembrolizumab

Until disease progression or unacceptable toxicity

Regular visits for safety and efficacy assessments

Phase 2A

Phase 2A cohorts to assess antitumor activity in specific cancer types

Until disease progression or unacceptable toxicity

Regular visits for tumor response assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment

30-90 days post-treatment

Follow-up visits for safety assessments

Treatment Details

Interventions

• LNS8801 (Small molecule)
• Pembrolizumab (PD-1 Inhibitor)

Trial Overview The trial is testing LNS8801 alone and combined with Pembrolizumab in patients with various solid tumors. It includes dose escalation to find the maximum tolerated dose (MTD) and expansion phases to assess safety, tolerability, pharmacokinetics (PK), and anti-tumor effects.

Participant Groups

Group I: Active Experimental Treatment 2 Interventions

Phase 1/2 open-label

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Memorial Sloan Kettering Cancer Center New York, NY

University of Pennsylvania Philadelphia, PA

The START Center for Cancer Care San Antonio, TX

Cedars-Sinai Medical Center Los Angeles, CA

More Trial Locations

Who Is Running the Clinical Trial?

Linnaeus Therapeutics, Inc.

Lead Sponsor

Trials

2

Patients Recruited

340+

Merck Sharp & Dohme LLC

Industry Sponsor

Trials

4096

Patients Recruited

5,232,000+

Findings from Research

Pembrolizumab (Keytruda) is the first anti-PD-1 therapy approved in the US for treating advanced malignant melanoma, specifically for patients who have progressed after prior treatments.

It is designed to target the PD-1 protein, enhancing the immune system's ability to fight cancer, and is currently under review for approval in the EU.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab: first global approval. Poole, RM.[2021]

Pembrolizumab (KEYTRUDA) was approved by the FDA for treating advanced melanoma, showing an overall response rate of 24% in a trial of 89 patients, with 86% of responses lasting at least 6 months.

While there are potential immune-mediated side effects, the benefits of prolonged tumor response durations were deemed to outweigh these risks, marking an improvement over existing treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. Chuk, MK., Chang, JT., Theoret, MR., et al.[2021]

In a phase II trial involving 15 patients with resectable non-small cell lung cancer (NSCLC), neoadjuvant treatment with pembrolizumab showed a major pathologic response in 27% of patients, indicating promising antitumor activity before surgery.

The treatment was found to be feasible and safe, with only 33% of patients experiencing moderate adverse events, and no postoperative mortality, suggesting that pembrolizumab does not compromise surgical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. Eichhorn, F., Klotz, LV., Kriegsmann, M., et al.[2022]

Pembrolizumab, an immune checkpoint inhibitor, can cause pneumonitis in 1%-5% of patients, and this case report highlights an atypical presentation of this side effect in a patient with metastatic squamous cell carcinoma.

The patient was successfully treated with steroid therapy after ruling out other potential causes, leading to complete resolution of the pneumonitis, emphasizing the importance of recognizing and managing atypical cases of checkpoint inhibitor-pneumonitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. Jeon, WJ., Nguyen, J., Castillo, DR., et al.[2023]

References

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

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. [2017]

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

FDA Approval Summary: Pembrolizumab for Treatment of Metastatic Non-Small Cell Lung Cancer: First-Line Therapy and Beyond. [2022]

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

Pembrolizumab: first global approval. [2021]

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

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. [2021]

5. Ireland pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. [2022]

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

Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. [2023]

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

FDA Approval Summary: Pembrolizumab for the Treatment of Patients with Unresectable or Metastatic Melanoma. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Evaluation of efficacy and safety of different pembrolizumab dose/schedules in treatment of non-small-cell lung cancer and melanoma: a systematic review. [2018]

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

Clinical performance of endobronchial ultrasound-guided transbronchial needle aspiration for assessing programmed death ligand-1 expression in nonsmall cell lung cancer. [2018]