PLN-101095 + Pembrolizumab for Advanced Cancer

Recruiting at 4 trial locations

Overseen By Pliant Therapeutics Medical Monitor

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Pliant Therapeutics, Inc.

Must be taking: Pembrolizumab

Must not be taking: Immunotherapy, Chemotherapy

Disqualifiers: Immune conditions, CNS metastases, others

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

77 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new cancer treatment that combines PLN-101095 (an experimental treatment) and pembrolizumab, focusing on safety and early signs of effectiveness. It targets individuals with advanced solid tumors who have previously taken pembrolizumab but have experienced cancer recurrence or progression. Those whose tumors have advanced despite treatment and who lack other effective options might be suitable candidates. As a Phase 1 trial, this research seeks to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications before starting. You must not have had pembrolizumab within 21 days, other immunotherapies within 4 weeks, radiotherapy within 1 week (for bone therapy) or 4 weeks (for other types), chemotherapy or targeted therapies within 2 weeks, and cell therapy within 12 months before the first dose of the study treatment.

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

Research has shown that PLN-101095, used alone or with pembrolizumab, demonstrates promising safety results. PLN-101095 was generally well-tolerated at various doses, with no major safety issues reported in early trials. The combination with pembrolizumab was also safe and effective, particularly for tumors resistant to other treatments. Pembrolizumab, a well-known cancer drug, is usually safe but can have some side effects. Overall, early findings suggest that the combination treatment is manageable for patients. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about PLN-101095 in combination with Pembrolizumab because it targets cancer in a novel way that could enhance the immune system's ability to fight tumors. While standard treatments often rely on chemotherapy or radiation, this combination leverages Pembrolizumab's role as a checkpoint inhibitor that unblocks immune cells, alongside PLN-101095, which may further boost this effect. This unique approach has the potential to improve outcomes for patients with advanced cancer by making the immune response more effective against the disease.

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

Research has shown that PLN-101095 yields promising results for treating advanced solid tumors, particularly in patients who no longer respond to pembrolizumab. In this trial, some participants will receive PLN-101095 as monotherapy, while others will receive it combined with pembrolizumab. Earlier studies demonstrated that PLN-101095 helped shrink tumors in 50% of patients who received the highest dose. When used with pembrolizumab, early data indicated that the combination was safe and effective, with 42.3% of patients showing a positive response. These findings suggest that PLN-101095, either alone or with pembrolizumab, could benefit patients with advanced cancers that have stopped responding to other treatments. ^{1 2 3 4 5}

Who Is on the Research Team?

Pliant Therapeutics Medical Monitor

Principal Investigator

Pliant Therapeutics, Inc.

Are You a Good Fit for This Trial?

This trial is for adults with advanced or metastatic solid tumors who have not responded to treatment with pembrolizumab after at least 3 months. Participants must have a type of tumor for which pembrolizumab is already indicated.

Inclusion Criteria

Estimated survival of ≥3 months

My cancer is confirmed to be advanced through testing.

I have no other effective treatment options for my cancer.

Exclusion Criteria

I had radiation for bone pain within the last week or other radiation within the last month.

I do not have immune conditions that pembrolizumab could worsen.

I have not taken pembrolizumab in the last 21 days.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Consecutive dose-escalation cohorts using a Bayesian optimal interval (BOIN) dose escalation design

Varies

Dose Expansion

Dose-expansion cohorts using Simon's 2-stage design

Varies

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Pembrolizumab
• PLN-101095

Trial Overview The study tests PLN-101095 in combination with pembrolizumab, assessing safety and how well it works against tumors. It has two parts: first, finding the right dose; second, expanding that dose to more people to see its effects.

How Is the Trial Designed?

Group I: Part 2 Dose Expansion: PLN-101095 in combination with Pembrolizumab Experimental Treatment 2 Interventions

Group II: Part 1 Dose Escalation: PLN-101095 given as monotherapy and in combination with Pembrolizumab Experimental Treatment 2 Interventions

Pembrolizumab is already approved in United States, European Union, United Kingdom for the following indications:

Approved in United States as KEYTRUDA for:

• Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
• Melanoma
• Non-small cell lung cancer (NSCLC)
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Hepatocellular carcinoma
• Renal cell carcinoma
• Cervical cancer
• Endometrial carcinoma

Approved in European Union as KEYTRUDA for:

• Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
• Melanoma
• Non-small cell lung cancer (NSCLC)
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Hepatocellular carcinoma
• Renal cell carcinoma
• Cervical cancer
• Endometrial carcinoma

Approved in United Kingdom as KEYTRUDA for:

• Untreated metastatic or unresectable recurrent head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1

Who Is Running the Clinical Trial?

Pliant Therapeutics, Inc.

Lead Sponsor

Trials

8

Recruited

720+

Published Research Related to This Trial

In a phase 1a/b trial involving 26 patients with PD-L1-positive non-small cell lung cancer (NSCLC), the combination of ramucirumab and pembrolizumab showed a manageable safety profile, with 84.6% experiencing treatment-related adverse events, primarily hypertension.

The treatment demonstrated promising efficacy, with an objective response rate of 42.3%, and particularly strong results in patients with high PD-L1 expression (TPS ≥ 50%), who had a median progression-free survival that was not reached.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1 Expansion Cohort of Ramucirumab Plus Pembrolizumab in Advanced Treatment-Naive NSCLC. Herbst, RS., Arkenau, HT., Bendell, J., et al.[2023]

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]

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 real-life study of 121 patients with advanced non-squamous non-small cell lung cancer, the combination of pembrolizumab and chemotherapy resulted in a median progression-free survival of 9 months and overall survival of 20.6 months, demonstrating its efficacy as a first-line treatment.

The treatment was generally well-tolerated, with manageable side effects; however, 17.5% of patients experienced grade 3-4 adverse events, and there were two treatment-related deaths, indicating the need for careful monitoring during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab plus pemetrexed-carboplatin combination in first-line treatment of advanced non-squamous non-small cell lung cancer: a multicenter real-life study (CAP29). Renaud, E., Ricordel, C., Corre, R., et al.[2023]

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 used in cancer treatment, can lead to rare but serious immune-related adverse events, including type 1 diabetes mellitus, occurring in about 0.2% of cases.

A review of 42 cases revealed that patients may develop diabetic ketoacidosis during treatment, highlighting the need for blood glucose monitoring and awareness of this potential side effect among clinicians.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Programmed Cell Death-1 Inhibitor-Induced Type 1 Diabetes Mellitus. Clotman, K., Janssens, K., Specenier, P., et al.[2022]

Pembrolizumab (Keytruda) is an effective treatment for advanced melanoma, showing significant improvements in progression-free survival and overall response rates compared to ipilimumab and chemotherapy in clinical trials involving patients with varying treatment histories.

The drug has a manageable safety profile, with immune-related side effects that are generally reversible, making it a valuable option for patients who have not responded to other therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab: A Review in Advanced Melanoma. Deeks, ED.[2022]

In a Phase 2 study involving 35 patients with non-small cell lung cancer, neoadjuvant pembrolizumab was found to be safe and well tolerated, with only one surgery delay due to thyroiditis and no mortality within 90 days post-surgery.

The study showed a high rate of R0 resection (88%) and a major pathologic response in 28% of patients, indicating that pembrolizumab may be more effective than standard neoadjuvant chemotherapy in this setting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Perioperative outcomes of pulmonary resection after neoadjuvant pembrolizumab in patients with non-small cell lung cancer. Tong, BC., Gu, L., Wang, X., et al.[2022]

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]

Citations

1. onclive.com onclive.com/view/pln-101095-pembrolizumab-has-early-activity-in-ici-refractory-advanced-solid-tumors

PLN-101095/Pembrolizumab Has Early Activity in ICI ... PLN-101095 plus pembrolizumab was safe and active in immune checkpoint inhibitor–refractory advanced solid tumors.

2. ir.pliantrx.com ir.pliantrx.com/news-releases/news-release-details/pliant-therapeutics-announces-interim-phase-1-data-pln-101095

Pliant Therapeutics Announces Interim Phase 1 Data for ... Antitumor activity observed with confirmed partial responses in 50% of patients at highest dose tested to date, across multiple tumor types.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06270706

A Phase 1 Study of PLN-101095 in Adults With Advanced ... This is a Phase 1a/1b, dose-escalation/expansion, consecutive-cohort, open-label study to evaluate the safety, tolerability, PK, PD, and preliminary evidence of ...

4. withpower.com withpower.com/trial/phase-1-solid-metastatic-tumor-7-2023-bdc91

PLN-101095 + Pembrolizumab for Advanced Cancer The treatment demonstrated promising efficacy, with an objective response rate of 42.3%, and particularly strong results in patients with high PD-L1 expression ...

5. ir.pliantrx.com ir.pliantrx.com/static-files/8273c374-cee9-435d-ad20-173b714c857b

PLN-101095 Phase 1 Trial Interim Results PLN-101095 showed antitumor activity in pembrolizumab-refractory patients. • Three confirmed partial responses (PR's) (3/6; ...