LNS8801 + Pembrolizumab for Cancer

Recruiting at 9 trial locations

Overseen By Mackenzie Tseng-Lee, MBA

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Linnaeus Therapeutics, Inc.

Must not be taking: Estrogen-based contraceptives

Disqualifiers: Thyroid cancer, Gall bladder cancer, others

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

Compensation: Varies

Number of Visits: 1

200 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new cancer treatment that combines two drugs: LNS8801 (an experimental treatment) and pembrolizumab. Researchers aim to assess the safety and effectiveness of this combination for individuals with advanced solid tumors or specific cancers, such as melanoma or lung cancer, who have not responded to other treatments. The trial will determine the optimal dosage and observe effects on tumor growth. Individuals with advanced cancer who have already undergone other treatments may be suitable candidates for this trial. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive it.

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.

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

Research has shown that combining LNS8801 and pembrolizumab is generally safe for people. An earlier study found that using LNS8801 alone or with pembrolizumab was safe and well-tolerated by cancer patients, with no major safety issues reported. Participants in this trial can feel reasonably confident about the safety of these treatments based on current evidence. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about LNS8801 combined with Pembrolizumab because it offers a fresh approach to cancer treatment. Most cancer therapies work by directly attacking cancer cells or boosting the immune system to do so. However, LNS8801 is unique as it specifically targets the G-protein coupled estrogen receptor (GPER), potentially enhancing the immune response and improving the effectiveness of Pembrolizumab, a well-known immune checkpoint inhibitor. This combination might offer improved outcomes for patients by not only inhibiting cancer growth but also enhancing the body's natural ability to fight cancer.

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

Research has shown that LNS8801 might slow cancer growth by lowering levels of a protein called MYC. Early results indicate that LNS8801 is safe and tolerable both alone and with pembrolizumab in people with advanced solid tumors. In this trial, participants will receive the combination of LNS8801 and pembrolizumab, which aims to boost the immune system's ability to fight cancer. A five-year study proved that pembrolizumab helps patients with certain cancers, like advanced lung cancer, live longer. Initial findings suggest that this combination could offer a new way to treat various cancers. ^{2 6 7 8 9}

Who Is on the Research Team?

Tina Garyantes, PhD

Principal Investigator

Linnaeus Therapeutics, Inc.

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• LNS8801
• Pembrolizumab

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.

How Is the Trial Designed?

Group I: Active Experimental Treatment 2 Interventions

Phase 1/2 open-label

LNS8801 is already approved in United States for the following indications:

Approved in United States as LNS8801 for:

• Orphan drug designation for metastatic cutaneous melanoma

Who Is Running the Clinical Trial?

Linnaeus Therapeutics, Inc.

Lead Sponsor

Trials

2

Recruited

340+

Merck Sharp & Dohme LLC

Industry Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Published Research Related to This Trial

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 metastatic non-small cell lung cancer (mNSCLC) in patients with tumors expressing PD-L1, showing significant improvements in overall survival (OS) and progression-free survival (PFS) in two major clinical trials with thousands of participants.

In the KEYNOTE-024 trial, pembrolizumab demonstrated a 40% reduction in the risk of death compared to chemotherapy, while in the KEYNOTE-010 trial, it also showed a significant survival advantage over chemotherapy in patients who had previously progressed on treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for Treatment of Metastatic Non-Small Cell Lung Cancer: First-Line Therapy and Beyond. Pai-Scherf, L., Blumenthal, GM., Li, H., et al.[2022]

A systematic review of four trials involving 3425 patients found that lower doses of pembrolizumab (2 mg/kg every 3 weeks) are equally effective as higher doses (10 mg/kg) in treating advanced melanoma and non-small-cell lung cancer (NSCLC).

The safety profile of pembrolizumab was similar across different doses, suggesting that the lower dose may be sufficient for routine treatment without compromising efficacy.

NCBI (Pubmed)

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. Abdel-Rahman, O.[2018]

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]

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]

Pembrolizumab (KEYTRUDA) was approved by the FDA for treating unresectable or metastatic melanoma based on two clinical trials involving 1,374 patients, showing significant improvements in overall survival compared to ipilimumab, with hazard ratios indicating a reduced risk of death.

Patients receiving pembrolizumab also experienced significant improvements in progression-free survival, although some immune-mediated adverse reactions like hypothyroidism and pneumonitis were noted, highlighting the importance of monitoring for side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for the Treatment of Patients with Unresectable or Metastatic Melanoma. Barone, A., Hazarika, M., Theoret, MR., et al.[2022]

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, a PD-1 inhibitor, has demonstrated clinical effectiveness in treating various solid tumors, particularly in patients with PD-L1-positive non-small-cell lung cancer and unresectable/metastatic melanoma.

Early-phase trials and ongoing studies are focused on further confirming the clinical benefits of pembrolizumab in thoracic malignancies, highlighting its potential as a significant treatment option in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. Karim, S., Leighl, N.[2017]

A study of 112 patients with non-small cell lung cancer (NSCLC) found that EBUS TBNA is effective for obtaining samples suitable for PD-L1 testing, with 82% of samples adequate for all ancillary tests.

The results showed a high satisfaction rate for PD-L1 expression testing, with 86% of cases yielding satisfactory results and 32% of patients exhibiting high PD-L1 expression levels (>50%), which is important for treatment decisions with pembrolizumab.

NCBI (Pubmed)

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. Biswas, A., Leon, ME., Drew, P., et al.[2018]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04130516

NCT04130516 | Study Assessing MTD, Safety, Tolerability, ... Phase 1B expansion cohorts include a monotherapy cohort (LNS8801 alone) of melanoma patients (not uveal) who are now not eligible for additional anti-PD-1 ...

2. asco.org asco.org/abstracts-presentations/ABSTRACT407804

The effect of LNS8801 alone and in combination ... In the first-in-human dose escalation study, LNS8801 was safe and tolerable alone and in combination with pembrolizumab in patients with advanced solid tumors ( ...

3. mskcc.org mskcc.org/cancer-care/clinical-trials/22-132

A Phase I/IIA Study of LNS8801 with and without ... LNS8801 works to reduce levels of a growth protein called MYC. By reducing these levels, LNS8801 may slow the growth of cancer, shrink the cancer, and help the ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10082298/

Five-Year Outcomes With Pembrolizumab Versus ... We report 5-year results from the phase III KEYNOTE-042 study (ClinicalTrials.gov identifier: NCT02220894). Eligible patients with locally advanced/metastatic ...

5. cancer.gov cancer.gov/research/participate/clinical-trials/intervention/anti-lag-3-monoclonal-antibody?pn=1

Clinical Trials Using Anti-LAG-3 Monoclonal Antibody - NCI NCI supports clinical trials that test new and more effective ways to treat cancer. Find clinical trials studying anti-lag-3 monoclonal antibody.

6. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.9543

The effect of LNS8801 alone and in combination with ... In the first-in-human dose escalation study, LNS8801 was safe and tolerable alone and in combination with pembrolizumab in patients with ...

7. jitc.bmj.com jitc.bmj.com/content/11/Suppl_1/A716

627 The effect of LNS8801 in combination with ... In the first-in-human study, LNS8801 was safe and tolerable alone and in combination with pembrolizumab (NCT04130516). ... Immunotherapy of Cancer ...

8. asco.org asco.org/abstracts-presentations/ABSTRACT373558

Phase 1b study of the novel first-in-class G protein-coupled ... In the first-in-human dose escalation study, LNS8801 was safe and tolerable alone and in combination with pembrolizumab in patients with metastatic solid tumors ...

9. targetedonc.com targetedonc.com/view/fda-grants-orphan-drug-designation-to-lns8801-for-metastatic-cutaneous-melanoma

FDA Grants Orphan Drug Designation to LNS8801 for ... LNS8801 has proven to be safe, well-tolerated, and demonstrated clinical benefit in patients with advanced cancers. Now, the FDA has granted ...