FB849 + Pembrolizumab for Solid Tumors

Recruiting at 4 trial locations

Overseen By 1STBIO Information center

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: 1ST Biotherapeutics, Inc.

Must not be taking: Chemotherapy, Radiotherapy, Endocrine therapy

Disqualifiers: Allergy, Additional malignancy, Endocrine, others

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

Compensation: Varies

Number of Visits: 6

151 Participants Needed

Trial Summary

What is the purpose of this trial?

This is the first-in-human, multicenter, open-label Phase I/II study to investigate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics, and preliminary efficacy of FB849 alone and in combination with pembrolizumab in subjects with advanced solid tumors for whom no standard therapy is available.

Will I have to stop taking my current medications?

The trial requires that you stop any previous anti-cancer therapy, including chemotherapy, radiotherapy, or molecular targeted therapy, at least 4 weeks before starting the study treatment. Endocrine therapy must be stopped at least 2 weeks or 5 half-lives (whichever is shorter) before starting the study treatment.

What data supports the effectiveness of the drug FB849 + Pembrolizumab for solid tumors?

Pembrolizumab has shown effectiveness in treating various advanced cancers, such as non-small cell lung cancer and melanoma, by helping the immune system attack cancer cells. It has also demonstrated durable antitumor activity in patients with certain genetic markers in solid tumors, suggesting potential benefits when combined with other treatments like FB849. ^{1 2 3 4 5}

Is pembrolizumab safe for use in humans?

Pembrolizumab has been shown to have a manageable safety profile in various studies for conditions like advanced melanoma, non-small cell lung cancer, and colorectal cancer. ^{2 4 6 7 8}

What makes the drug FB849 + Pembrolizumab unique for treating solid tumors?

The combination of FB849 with Pembrolizumab is unique because it pairs a potentially novel agent (FB849) with Pembrolizumab, a drug that helps the immune system attack cancer cells by blocking a protein called PD-1. This combination may offer a new approach to treating solid tumors, especially if FB849 has a different mechanism of action or targets other pathways compared to existing treatments. ^{2 3 4 9 10}

Research Team

1STBIO Chief Development Officer

Principal Investigator

1ST Biotherapeutics

Eligibility Criteria

This trial is for adults over 18 with advanced solid tumors and no standard therapy options left. They must be able to understand the study, sign consent, have a measurable tumor lesion, be relatively active (ECOG status 0 or 1), and expected to live at least another three months. Their organs and bone marrow must function well.

Inclusion Criteria

I have at least one tumor that can be measured.

My organs and bone marrow are working well, as shown by recent tests.

Subject should understand, sign, and date the written ICF prior to screening.

Exclusion Criteria

I haven't had cancer treatment, including chemo, targeted therapy, or trials, within the last 4 weeks.

I have another cancer that is getting worse or needs treatment.

I cannot take pills due to severe nausea, vomiting, or issues with my digestive system.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase Ia Dose-Escalation

Participants receive FB849 monotherapy to determine the maximum tolerated dose and preliminary recommended Phase II dose using a Bayesian optimal interval design.

21 days per cycle

Multiple visits for dose escalation and monitoring

Phase Ib Dose-Expansion

Participants receive FB849 monotherapy at the preliminary RP2D to assess safety and anti-tumor activity.

21 days per cycle

Interim analysis and multiple visits for safety assessment

Phase IIa Dose-Escalation

Participants receive FB849 in combination with pembrolizumab to evaluate safety and anti-tumor activity.

21 days per cycle

At least 6 subjects per dose level with regular monitoring

Phase IIb Dose-Expansion

Participants with Type A, B, or C cancer receive FB849 in combination with pembrolizumab to further assess safety and anti-tumor activity.

21 days per cycle

Simon’s two-stage design with regular tumor assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment, with tumor assessments every 6 weeks initially, then every 12 weeks.

Up to 3 years

Regular imaging and safety assessments

Treatment Details

Interventions

• FB849

Trial Overview The trial is testing FB849 alone and in combination with pembrolizumab on different types of cancer (Type A, B, C). It's an early-stage study looking at how safe it is, what side effects occur, how the body processes it (PK), its impact on the body (pharmacodynamics), and if it works against cancer.

Participant Groups

Group I: Phase Ib dose-expansion of FB849 monotherapy Experimental Treatment 1 Intervention

Participations will receive FB849 orally once a day.

Group II: Phase Ia dose-escalation part of FB849 Monotherapy Experimental Treatment 1 Intervention

Participations will receive FB849 orally once a day.

Group III: Phase IIb dose-expansion part of FB849 in Combination with Pembrolizumab (Type C cancer) Experimental Treatment 1 Intervention

Participations will receive FB849 orally once a day in combination with pembrolizumab.

Group IV: Phase IIb dose-expansion part of FB849 in Combination with Pembrolizumab (Type B cancer) Experimental Treatment 1 Intervention

Participations will receive FB849 orally once a day in combination with pembrolizumab.

Group V: Phase IIb dose-expansion part of FB849 in Combination with Pembrolizumab (Type A cancer) Experimental Treatment 1 Intervention

Participations will receive FB849 orally once a day in combination with pembrolizumab.

Group VI: Phase IIa dose-escalation part of FB849 in Combination with Pembrolizumab Experimental Treatment 1 Intervention

Participations will receive FB849 orally once a day in combination with pembrolizumab.

Who Is Running the Clinical Trial?

1ST Biotherapeutics, Inc.

Lead Sponsor

Trials

3

Recruited

240+

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

In a study involving 351 patients with advanced noncolorectal MSI-H/dMMR solid tumors, pembrolizumab showed a significant objective response rate (ORR) of 30.8%, indicating its efficacy in this patient population.

The treatment demonstrated a long median duration of response of 47.5 months and manageable safety, with only 11.1% of patients experiencing severe (grade 3-4) treatment-related adverse events, supporting its use in heavily pretreated cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab in microsatellite instability high or mismatch repair deficient cancers: updated analysis from the phase II KEYNOTE-158 study. Maio, M., Ascierto, PA., Manzyuk, L., 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]

A 68-year-old patient with stage IV lung adenocarcinoma showed an unexpected positive response to paclitaxel after failing treatment with pembrolizumab, an anti-PD-1 immunotherapy.

The patient experienced a response duration of over fourteen months with paclitaxel, suggesting that combining or sequencing chemotherapy with immunotherapy may enhance treatment effectiveness in certain cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Prolonged response with paclitaxel after immunotherapy by pembrolizumab in lung cancer]. Zapata, E., Mennecier, B., Leduc, C., et al.[2017]

In a study of 100 patients with non-small cell lung cancer (NSCLC) treated with pembrolizumab, further stratification of PD-L1 tumor proportion score (TPS) beyond 50% did not significantly affect progression-free survival (PFS).

Smoking status was associated with improved PFS, while prior radiotherapy was linked to decreased PFS, indicating that these factors, along with performance status, may serve as important biomarkers for predicting response to pembrolizumab treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab monotherapy for non-small cell lung cancer (NSCLC): can patient stratification be improved in the UK Tayside population? A retrospective cohort study. Mander, ES., Merrick, CB., Nicholson, HA., et al.[2023]

In a study of 38 patients with p16+ oropharyngeal squamous cell carcinoma, there was a 76% agreement in PD-L1 combined positive scores (CPS) between primary tumors and lymph node metastases, indicating variability in scoring between these specimens.

The interobserver agreement for CPS scoring was fair to substantial, suggesting that additional evaluations may be necessary to ensure accurate scoring, especially for patients who might benefit from immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Programmed Death Ligand-1 Combined Positive Score Concordance and Interrater Reliability in Primary Tumors and Synchronous Lymph Node Metastases in Resected Cases of p16+ Oropharyngeal Squamous Cell Carcinoma. Kaur, A., Kuchta, K., Watkin, W., et al.[2023]

In a study of 88 advanced melanoma patients treated with pembrolizumab, 81.8% experienced any-grade toxicities, with skin and gastrointestinal issues being the most common side effects.

Despite the high incidence of side effects, pembrolizumab was found to be well tolerated in real-world settings, and severe toxicities were manageable with systemic steroids.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world experience with pembrolizumab toxicities in advanced melanoma patients: a single-center experience in the UK. So, AC., Board, RE.[2022]

In the final analysis of the KEYNOTE-164 study, pembrolizumab demonstrated a 32.8% objective response rate in patients with advanced MSI-H/dMMR colorectal cancer who had received multiple prior treatments, indicating its efficacy in this difficult-to-treat population.

The treatment was associated with a median overall survival of 31.4 months for patients with more prior therapies and 47.0 months for those with fewer, while maintaining a manageable safety profile with no new safety concerns reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for previously treated, microsatellite instability-high/mismatch repair-deficient advanced colorectal cancer: final analysis of KEYNOTE-164. Le, DT., Diaz, LA., Kim, TW., et al.[2023]

The ongoing KEYNOTE-495/KeyImPaCT study is evaluating the effectiveness of pembrolizumab combined with other therapies in advanced non-small cell lung cancer (NSCLC), with results showing varying objective response rates (ORR) based on tumor characteristics, ranging from 0-12% in low T-cell-inflamed groups to 50-60% in high T-cell-inflamed groups.

The study confirms that assessing T-cell-inflamed gene expression profiles (TcellinfGEP) and tumor mutational burden (TMB) can help identify which patients are more likely to benefit from pembrolizumab-based treatments, while the safety profiles of the combinations remain consistent with previous findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biomarker-directed, pembrolizumab-based combination therapy in non-small cell lung cancer: phase 2 KEYNOTE-495/KeyImPaCT trial interim results. Gutierrez, M., Lam, WS., Hellmann, MD., et al.[2023]

In a phase II study involving 110 patients with advanced clear cell renal cell carcinoma (ccRCC), pembrolizumab demonstrated a 36.4% objective response rate, indicating significant antitumor activity as a first-line treatment.

The treatment was generally well-tolerated, with 30% of patients experiencing grade 3-5 adverse events, primarily colitis and diarrhea, which aligns with safety profiles observed in other cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Open-Label, Single-Arm Phase II Study of Pembrolizumab Monotherapy as First-Line Therapy in Patients With Advanced Clear Cell Renal Cell Carcinoma. McDermott, DF., Lee, JL., Bjarnason, GA., et al.[2022]

In a phase 3 trial involving 305 patients with advanced non-small-cell lung cancer (NSCLC) expressing PD-L1, pembrolizumab significantly improved median progression-free survival to 10.3 months compared to 6.0 months with chemotherapy, indicating its efficacy as a treatment option.

Patients receiving pembrolizumab also experienced fewer treatment-related adverse events (73.4% vs. 90.0% for chemotherapy), highlighting its safety profile alongside its effectiveness in prolonging survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab versus Chemotherapy for PD-L1-Positive Non-Small-Cell Lung Cancer. Reck, M., Rodríguez-Abreu, D., Robinson, AG., et al.[2022]

References

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

Pembrolizumab in microsatellite instability high or mismatch repair deficient cancers: updated analysis from the phase II KEYNOTE-158 study. [2022]

2. 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]

3. France pubmed.ncbi.nlm.nih.gov

[Prolonged response with paclitaxel after immunotherapy by pembrolizumab in lung cancer]. [2017]

4. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab monotherapy for non-small cell lung cancer (NSCLC): can patient stratification be improved in the UK Tayside population? A retrospective cohort study. [2023]

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

Programmed Death Ligand-1 Combined Positive Score Concordance and Interrater Reliability in Primary Tumors and Synchronous Lymph Node Metastases in Resected Cases of p16+ Oropharyngeal Squamous Cell Carcinoma. [2023]

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

Real-world experience with pembrolizumab toxicities in advanced melanoma patients: a single-center experience in the UK. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab for previously treated, microsatellite instability-high/mismatch repair-deficient advanced colorectal cancer: final analysis of KEYNOTE-164. [2023]

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

Biomarker-directed, pembrolizumab-based combination therapy in non-small cell lung cancer: phase 2 KEYNOTE-495/KeyImPaCT trial interim results. [2023]

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

Open-Label, Single-Arm Phase II Study of Pembrolizumab Monotherapy as First-Line Therapy in Patients With Advanced Clear Cell Renal Cell Carcinoma. [2022]

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

Pembrolizumab versus Chemotherapy for PD-L1-Positive Non-Small-Cell Lung Cancer. [2022]