FF-10832 + Pembrolizumab for Cancer

Recruiting at 20 trial locations

Overseen By FPHU Study Coordinator

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Fujifilm Pharmaceuticals U.S.A., Inc.

Must not be taking: Anti-PD-1, Anti-PD-L1

Disqualifiers: Pregnancy, Recent radiotherapy, Organ transplant, 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

Compensation: Varies

Number of Visits: 2

120 Participants Needed

Trial Summary

What is the purpose of this trial?

To confirm a recommended Phase 2 dose (RP2D) of FF-10832 (Gemcitabine Liposome Injection) given intravenously Day 1 of a 21-day cycle, in combination with 200 mg pembrolizumab given intravenously Day 1 of the same 21-day cycle, for treatment of advanced urothelial and non-small cell lung cancer

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications, but you must not have received any systemic anti-cancer therapy within 4 weeks before starting the trial.

What data supports the effectiveness of the drug FF-10832 + Pembrolizumab for cancer?

Research shows that FF-10832, a liposomal form of gemcitabine, improves stability in the blood and targets tumors more effectively, enhancing its cancer-fighting ability. Additionally, gemcitabine has been shown to improve outcomes in pancreatic cancer, and combining it with immunotherapy like pembrolizumab may increase its effectiveness. ^{1 2 3 4 5}

Is the combination of FF-10832 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 reactions such as pneumonitis (lung inflammation) and thyroid disorders. While specific safety data for FF-10832 combined with Pembrolizumab is not provided, Pembrolizumab alone has been studied extensively and has known safety profiles. ^{6 7 8 9 10}

What makes the drug FF-10832 + Pembrolizumab unique for cancer treatment?

This treatment combines FF-10832, a novel formulation of gemcitabine in a liposome (a tiny bubble made from the same material as a cell membrane) to enhance delivery, with pembrolizumab, an immune checkpoint inhibitor that helps the immune system attack cancer cells. This combination aims to improve the effectiveness of cancer treatment by both directly targeting cancer cells and boosting the body's immune response. ^{6 10 11 12 13}

Eligibility Criteria

Adults (18+) with advanced solid tumors that have worsened after standard treatments, or those who cannot tolerate or refuse such treatments. They must be able to consent, have a life expectancy of at least 3 months, and an ECOG performance status of 0-1. Pregnant individuals, recent recipients of certain cancer therapies or vaccines, and patients with specific genetic mutations not previously treated are excluded.

Inclusion Criteria

Patient must have a life expectancy of ≥ 3 months

I have urothelial or NSCLC cancer and previous treatments targeting PD-1 or PD-L1 didn't work for me.

My cancer has spread, didn't respond to standard treatments, or I can't tolerate/refuse them.

Exclusion Criteria

I have not had a live vaccine in the last 30 days.

I have received an organ or tissue transplant from another person.

Positive urine pregnancy test within 72 hours prior to treatment

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Safety Run-in

Initial phase to evaluate safety and tolerability of FF-10832 in combination with pembrolizumab

21 days

1 visit (in-person) per cycle

Expansion Treatment

Participants receive either monotherapy or combination therapy in randomized cohorts for further safety and efficacy evaluation

21-day cycles, up to 7 years

1 visit (in-person) per cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

7 years

Treatment Details

Interventions

• FF-10832
• Pembrolizumab

Trial Overview The trial is testing the combination of FF-10832 (a liposome injection) and Pembrolizumab in adults with advanced solid tumors. FF-10832 is given intravenously on Day 1 every three weeks alongside Pembrolizumab to determine the safety and effective dose for Phase 2 trials.

Participant Groups

Group I: Urothelial Monotherapy - FF-10832 Expansion Phase Experimental Treatment 1 Intervention

FF-10832 will be dosed at 40 mg/m2

Group II: Urothelial Combination - FF-10832 + pembrolizumab Expansion Phase Experimental Treatment 2 Interventions

FF-10832 in combination therapy with pembrolizumab; FF-10832 will be dosed at 40 mg/m2 with a fixed dose of pembrolizumab (200 mg)

Group III: Safety Run-in Phase Experimental Treatment 2 Interventions

FF-10832 in combination therapy with pembrolizumab; FF-10832 will be dosed at 40 mg/m2 with a fixed dose of pembrolizumab (200 mg)

Group IV: NSCLC Monotherapy - FF-10832 Expansion Phase Experimental Treatment 1 Intervention

FF-10832 will be dosed at 40 mg/m2

Group V: NSCLC Combination - FF-10832 + pembrolizumab Expansion Phase Experimental Treatment 2 Interventions

FF-10832 in combination therapy with pembrolizumab; FF-10832 will be dosed at 40 mg/m2 with a fixed dose of pembrolizumab (200 mg)

FF-10832 is already approved in United States for the following indications:

Approved in United States as Gemcitabine Liposome Injection for:

• Advanced urothelial cancer
• Non-small cell lung cancer

Who Is Running the Clinical Trial?

Fujifilm Pharmaceuticals U.S.A., Inc.

Lead Sponsor

Trials

9

Recruited

680+

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

Findings from Research

Liposomal encapsulation of gemcitabine (FF-10832) significantly improved its pharmacokinetics, showing 672 times higher plasma levels and 1047 times higher tumor levels compared to unencapsulated gemcitabine in mouse models of pancreatic cancer.

FF-10832 demonstrated better antitumor activity and tolerability than standard gemcitabine, indicating its potential as a more effective treatment option for pancreatic cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Liposomal Gemcitabine, FF-10832, Improves Plasma Stability, Tumor Targeting, and Antitumor Efficacy of Gemcitabine in Pancreatic Cancer Xenograft Models. Matsumoto, T., Komori, T., Yoshino, Y., et al.[2022]

In a phase 3 trial involving 451 patients with resected pancreatic adenocarcinoma, the addition of gemcitabine to fluorouracil-based chemoradiation showed a trend towards improved survival, with a median survival of 20.5 months for the gemcitabine group compared to 16.9 months for the fluorouracil group.

However, gemcitabine was associated with significantly higher grade 4 hematologic toxicity (14% vs. 1% for fluorouracil), indicating a trade-off between potential survival benefits and increased side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fluorouracil vs gemcitabine chemotherapy before and after fluorouracil-based chemoradiation following resection of pancreatic adenocarcinoma: a randomized controlled trial. Regine, WF., Winter, KA., Abrams, RA., et al.[2022]

In a clinical trial involving 5 patients with inoperable locally advanced pancreatic cancer, a combination therapy of gemcitabine and dendritic cell vaccination was found to be safe, with no serious treatment-related adverse events reported.

Three out of the 5 patients showed effective responses, including one case of partial remission and two cases of stable disease lasting over 6 months, suggesting that this combined approach can enhance the immune response against tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A combination therapy of gemcitabine with immunotherapy for patients with inoperable locally advanced pancreatic cancer. Hirooka, Y., Itoh, A., Kawashima, H., et al.[2022]

Liposomal formulation of gemcitabine (GemLip) significantly inhibited tumor growth in hormone-refractory prostate cancer (HRPCa) models, outperforming conventional gemcitabine, especially at lower doses.

GemLip not only enhanced the anti-tumoral effects but also reduced metastases in the liver and spleen, demonstrating its potential as a more effective treatment option for HRPCa compared to standard gemcitabine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Liposomal gemcitabine (GemLip)-efficient drug against hormone-refractory Du145 and PC-3 prostate cancer xenografts. Jantscheff, P., Esser, N., Graeser, R., et al.[2022]

In a phase II trial involving 200 patients with advanced pancreatic cancer, the combination of gemcitabine (GEM) and cationic liposome-embedded paclitaxel (EndoTAG™-1) showed improved overall survival (OS) and progression-free survival (PFS) compared to GEM alone, with median OS of 9.3 months for the highest ET dose group versus 6.8 months for GEM alone.

The treatment was generally well tolerated, with manageable and reversible side effects, primarily mild thrombocytopenia and infusion reactions, indicating a favorable safety profile for the combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cationic liposomal paclitaxel plus gemcitabine or gemcitabine alone in patients with advanced pancreatic cancer: a randomized controlled phase II trial. Löhr, JM., Haas, SL., Bechstein, WO., 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 (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 (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]

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, 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, a monoclonal antibody targeting PD-1, showed significant efficacy in treating a 79-year-old patient with advanced squamous cell lung cancer, leading to a complete response after just 3 cycles of treatment.

However, the patient developed acute myelomonocytic leukemia after starting pembrolizumab, highlighting a potential safety concern that warrants further investigation into the drug's effects on blood cell production.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute myelomonocytic leukemia during pembrolizumab treatment for non-small cell lung cancer: A case report. Kim, HB., Park, SG., Hong, R., et al.[2020]

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 approved treatment for metastatic or locally advanced esophageal and gastroesophageal junction cancer, indicating its efficacy in targeting these specific cancer types.

It is used in combination with platinum- and fluoropyrimidine-based chemotherapy, suggesting a synergistic approach to enhance treatment effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab Approved for Esophageal or Gastroesophageal Cancer. Aschenbrenner, DS.[2023]

References

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

A Liposomal Gemcitabine, FF-10832, Improves Plasma Stability, Tumor Targeting, and Antitumor Efficacy of Gemcitabine in Pancreatic Cancer Xenograft Models. [2022]

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

Fluorouracil vs gemcitabine chemotherapy before and after fluorouracil-based chemoradiation following resection of pancreatic adenocarcinoma: a randomized controlled trial. [2022]

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

A combination therapy of gemcitabine with immunotherapy for patients with inoperable locally advanced pancreatic cancer. [2022]

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

Liposomal gemcitabine (GemLip)-efficient drug against hormone-refractory Du145 and PC-3 prostate cancer xenografts. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Cationic liposomal paclitaxel plus gemcitabine or gemcitabine alone in patients with advanced pancreatic cancer: a randomized controlled phase II trial. [2023]

6. 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]

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

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

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

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

9. England pubmed.ncbi.nlm.nih.gov

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

10. England pubmed.ncbi.nlm.nih.gov

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

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

Acute myelomonocytic leukemia during pembrolizumab treatment for non-small cell lung cancer: A case report. [2020]

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

Programmed Cell Death-1 Inhibitor-Induced Type 1 Diabetes Mellitus. [2022]

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

Pembrolizumab Approved for Esophageal or Gastroesophageal Cancer. [2023]