Pembrolizumab + Pemetrexed for Bone Cancer

Overseen By Naveed Wagle, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Saint John's Cancer Institute

Must be taking: Folic acid, Vitamin B12, Dexamethasone

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: Immunodeficiency, Autoimmune disease, HIV, others

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

Prior Safety Data This treatment has passed at least one previous human trial

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

Compensation: Varies

Number of Visits: 1

Duration: Up to 2 years or until disease progression

21 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the combination of two drugs, pembrolizumab (an immunotherapy) and pemetrexed (a chemotherapy), to assess their effectiveness in treating chordoma, a rare bone cancer. The main goal is to determine how many patients experience tumor shrinkage or disappearance with this treatment. Researchers will also examine side effects, the duration patients live without cancer progression, and overall quality of life during the study. Individuals diagnosed with chordoma whose disease has worsened in the last six months might be suitable candidates for this trial. As a Phase 2 trial, the research focuses on evaluating the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, you must be able to interrupt non-steroidal anti-inflammatory drugs (NSAIDs) around the time of Pemetrexed administration.

Is there any evidence suggesting that pembrolizumab and pemetrexed are likely to be safe for humans?

Research has shown that the combination of pembrolizumab and pemetrexed has been studied for safety in patients with various types of cancer. Past studies found this combination to be safe. Specifically, in lung cancer patients, it proved effective and generally well-tolerated, with most side effects manageable through standard medical care.

Real-world studies identified common side effects such as low platelet counts and changes in kidney function. However, these effects are typical for chemotherapy treatments and were usually not severe.

This combination has also been used successfully in other cancers, with long-term data indicating it can help improve survival. While side effects can occur, they often resemble those seen with other cancer treatments and can usually be managed with routine medical care.

Overall, this combination shows promise, but it is important to weigh the benefits against the potential side effects. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for bone cancer?

Researchers are excited about the combination of pembrolizumab and pemetrexed for treating bone cancer because it offers a novel approach compared to the current standard of care, which typically involves chemotherapy and radiation. Pembrolizumab is an immunotherapy drug that works by blocking a protein called PD-1, allowing the immune system to better attack cancer cells. Pemetrexed, on the other hand, is a chemotherapy agent that disrupts cancer cell growth. By combining these two treatments, there's potential to enhance the body's immune response while directly targeting the cancer cells, possibly leading to more effective outcomes with fewer side effects.

What evidence suggests that pembrolizumab and pemetrexed might be an effective treatment for chordoma?

Research has shown that using pembrolizumab and pemetrexed together yields promising results for treating various types of cancer. In lung cancer studies, patients receiving this combination lived longer and had smaller tumors. Pembrolizumab has been particularly effective against tumors that have spread to the bones, improving conditions both at the original site and where the cancer has spread. The KEYNOTE-189 study found that patients lived without their cancer worsening for about 9 months and lived for about 22 months overall when pembrolizumab was combined with chemotherapy. This trial will evaluate the potential benefits of this combination for patients with bone cancer, such as chordoma. ^{3 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for patients with chordoma, a type of bone cancer, who have seen their disease progress. Participants should meet certain health standards to be eligible but specific inclusion and exclusion criteria are not listed.

Inclusion Criteria

Evidence of progressive disease within the past six months before study entry, according to RECIST v1.1

Participant has measurable disease, according to RECIST v1.1

I can take folic acid, Vitamin B12, and dexamethasone as scheduled.

Exclusion Criteria

I have an autoimmune disease treated with strong medication in the last 2 years.

Participant has a known history of human immunodeficiency virus (HIV) infection

I have or had lung inflammation not caused by an infection.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive pembrolizumab 200 mg IV infusion and pemetrexed 900 mg/m2 IV infusion on Day 1 of each 21-day cycle

Up to 2 years or until disease progression

1 visit every 21 days (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 5 years

What Are the Treatments Tested in This Trial?

Interventions

• Pembrolizumab
• Pemetrexed

Trial Overview The study tests the effectiveness of Pembrolizumab combined with high-dose Pemetrexed in treating chordoma. It aims to measure how well tumors respond, control rate of the disease, overall survival time, progression-free survival at various intervals, tumor size changes over time, quality of life impacts and molecular changes in tumors.

How Is the Trial Designed?

Group I: Single Arm Experimental Treatment 2 Interventions

Eligible patients will receive pembrolizumab 200 mg IV infusion on Day 1 of each 21-day cycle, and pemetrexed 900 mg/m2 by intravenous (IV) infusion on Day 1 of each 21-day treatment cycle and supportive medications (folic acid, vitamin B12, and dexamethasone).

Who Is Running the Clinical Trial?

Saint John's Cancer Institute

Lead Sponsor

Trials

27

Recruited

6,800+

Chordoma Foundation

Collaborator

Trials

4

Recruited

100+

Published Research Related to This Trial

Pembrolizumab, when combined with carboplatin and pemetrexed, significantly improves overall and progression-free survival rates in patients with non-small cell lung cancer (NSCLC), demonstrating its efficacy as a treatment option.

This case report highlights a unique instance of immune-mediated sarcoidosis developing in a patient with NSCLC after receiving pembrolizumab, indicating potential immune-related side effects of this therapy that require further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pulmonary Sarcoidosis Activation following Neoadjuvant Pembrolizumab plus Chemotherapy Combination Therapy in a Patient with Non-Small Cell Lung Cancer: A Case Report. Fakhri, G., Akel, R., Salem, Z., et al.[2022]

Treatment with pembrolizumab, an immunotherapy drug, led to significant improvements in both lung tumors and bone metastases in two patients with advanced non-small cell lung cancer (NSCLC) and impending fractures.

After 3 months of treatment, both patients experienced a complete response, showing remarkable bone healing and reduced lung tumor size, suggesting that pembrolizumab may be an effective systemic therapy even in cases with severe bone complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Complete Response of Bone Metastasis in Non-small Cell Lung Cancer With Pembrolizumab: Two Case Reports. Asano, Y., Yamamoto, N., Hayashi, K., et al.[2021]

Pembrolizumab, an immunotherapy for advanced non-small-cell lung cancer (NSCLC), significantly improves progression-free and overall survival compared to traditional chemotherapy, with fewer side effects, particularly in patients with high PD-L1 expression (≥50%).

In combination with pemetrexed and carboplatin, pembrolizumab also enhances treatment effectiveness and maintains manageable toxicity, leading to a shift in first-line treatment strategies for advanced NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab as first-line therapy for metastatic non-small-cell lung cancer. Reck, M.[2018]

In a phase 2 trial involving 12 patients with advanced osteosarcoma, pembrolizumab showed no clinical benefit at 18 weeks, with all patients experiencing disease progression and a median overall survival of only 6.6 months.

Despite the lack of significant antitumor activity, pembrolizumab was well-tolerated, with no treatment-related deaths or severe adverse events, suggesting it may be safe for use in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab in advanced osteosarcoma: results of a single-arm, open-label, phase 2 trial. Boye, K., Longhi, A., Guren, T., et al.[2022]

In the KEYNOTE-189 study involving 616 patients with metastatic non-squamous non-small-cell lung cancer, the combination of pembrolizumab and pemetrexed-platinum significantly maintained quality of life (GHS/QOL) scores compared to placebo, with a notable improvement at week 21.

Patients receiving pembrolizumab also experienced a longer median time to deterioration in symptoms like cough and chest pain, although this result was not statistically significant, indicating potential benefits in symptom management with this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient-reported outcomes following pembrolizumab or placebo plus pemetrexed and platinum in patients with previously untreated, metastatic, non-squamous non-small-cell lung cancer (KEYNOTE-189): a multicentre, double-blind, randomised, placebo-controlled, phase 3 trial. Garassino, MC., Gadgeel, S., Esteban, E., et al.[2020]

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 the phase III KEYNOTE-189 study, pembrolizumab combined with pemetrexed and platinum-based chemotherapy significantly improved overall survival (OS) and progression-free survival (PFS) in patients with untreated metastatic nonsquamous non-small-cell lung cancer, with a hazard ratio of 0.56 for OS and 0.49 for PFS after a median follow-up of 31 months.

The treatment was associated with a high objective response rate (ORR) of 48.3% compared to 19.9% for the placebo group, and among patients who completed 35 cycles of pembrolizumab, the ORR was even higher at 85.7%, indicating strong efficacy with manageable toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pemetrexed plus platinum with or without pembrolizumab in patients with previously untreated metastatic nonsquamous NSCLC: protocol-specified final analysis from KEYNOTE-189. Rodríguez-Abreu, D., Powell, SF., Hochmair, MJ., et al.[2022]

In a study of 187 patients with non-small-cell lung cancer (NSCLC) and PD-L1 expression of ≥50%, those with PD-L1 levels of 90%-100% showed significantly better treatment outcomes with pembrolizumab, including a higher overall response rate (60% vs. 32.7%) and longer median progression-free survival (14.5 months vs. 4.1 months).

Patients with higher PD-L1 expression not only had improved response rates but also longer overall survival, indicating that PD-L1 levels can be a critical factor in predicting the efficacy of pembrolizumab as a first-line treatment for NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcomes to first-line pembrolizumab in patients with non-small-cell lung cancer and very high PD-L1 expression. Aguilar, EJ., Ricciuti, B., Gainor, JF., et al.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8825649/

Pembrolizumab monotherapy or combination therapy for ... The results of KEYNOTE-189 showed that the median PFS and OS of first-line pembrolizumab combined with chemotherapy were 9.0 and 22.0 months, respectively, ...

2. tandfonline.com tandfonline.com/doi/full/10.1080/25310429.2025.2457856

Outcomes of Pembrolizumab plus chemotherapy for ... However, the two-year survival rate of the Pembrolizumab combined with chemotherapy group, at 32.7%, is significantly higher than that of the chemotherapy alone ...

3. withpower.com withpower.com/trial/pembrolizumab-pemetrexed-for-bone-cancer-a0a7e

Pembrolizumab + Pemetrexed for Bone Cancer Research shows that Pembrolizumab, when used for lung cancer that has spread to the bones, can significantly improve both lung tumors and bone metastasis.

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.23.02747

Phase III KEYNOTE-789 Study of Pemetrexed and ... We report results from the randomized, double-blind, phase III KEYNOTE-789 study of pemetrexed and platinum–based chemotherapy with or without pembrolizumab

5. sciencedirect.com sciencedirect.com/science/article/pii/S095980492400162X/pdf

Real-world outcomes of Italian patients with advanced non ... Overall, our outcomes findings are concordant with other retrospective real-world studies that reported OS of 11.8–21.8 months, 1-year OS rate of 59.0–59.4%, ...

6. ascopubs.org ascopubs.org/doi/10.1200/JCO.22.01989

5-Year Outcomes From the Phase 3 KEYNOTE-189 Study Among 57 patients who completed 35 cycles of pembrolizumab, objective response rate was 86.0% and 3-year OS rate after completing 35 cycles ( ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12020046/

The real-world safety profile of pemetrexed and platinum ... This study utilized the FDA Adverse Event Reporting System (FAERS) to assess the safety of pemetrexed and platinum with or without pembrolizumab in LC patients.

8. asco.org asco.org/abstracts-presentations/ABSTRACT284185

Real-world safety of pemetrexed, carboplatin, and ... Real-world safety of pemetrexed, carboplatin, and pembrolizumab in U.S. NSCLC patients. ; Platelet count decreased, 94.7/31.8, 97.0/31.4 ; Serum creatinine ...

9. merck.com merck.com/news/five-year-data-for-mercks-keytruda-pembrolizumab-plus-chemotherapy-showed-sustained-survival-benefit-versus-chemotherapy-alone-in-two-studies-for-metastatic-non-small-cell-lung-cancer-nsclc/

Five-Year Data for Merck's KEYTRUDA® (pembrolizumab ... The KEYTRUDA-pemetrexed-platinum chemotherapy combination reduced the risk of death by 40% (HR=0.60 [95% CI, 0.50-0.72]). At five years, KEYTRUDA plus ...