VIR-5525 + Pembrolizumab for Solid Tumors

Recruiting at 2 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Vir Biotechnology, Inc.

Disqualifiers: Pregnancy, Infections, HIV, Hepatitis, 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

450 Participants Needed

Trial Summary

What is the purpose of this trial?

This Phase 1, first-in-human (FIH), dose-escalation and dose-expansion study is designed to evaluate the safety, PK, and preliminary anti-tumor activity of VIR-5525 as a monotherapy and in combination with pembrolizumab in participants with solid tumors that are known to express EGFR. The study will be conducted in the following 4 parts: * Part 1: VIR-5525 monotherapy dose escalation * Part 2: VIR-5525 monotherapy dose expansion * Part 3: VIR-5525 plus pembrolizumab dose escalation * Part 4: VIR-5525 plus pembrolizumab dose expansion

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 cannot have received prior systemic anti-cancer therapy within 5 half-lives of the drug or 28 days before the study starts, and you must not have had radiotherapy within 2 weeks of starting the study.

What data supports the effectiveness of the drug Pembrolizumab in treating solid tumors?

Pembrolizumab has been shown to improve survival in patients with advanced melanoma and is approved for treating certain types of lung cancer, demonstrating its effectiveness in fighting cancer by helping the immune system attack cancer cells. ^{1 2 3 4 5}

What is known about the safety of Pembrolizumab in humans?

Pembrolizumab is generally well tolerated and has a favorable safety profile, with common side effects including fatigue, rash, itching, and diarrhea. Less common immune-related side effects can include hypothyroidism (underactive thyroid), colitis (inflammation of the colon), hepatitis (liver inflammation), and pneumonitis (lung inflammation). ^{1 6 7 8 9}

What makes the drug VIR-5525 + Pembrolizumab unique for treating solid tumors?

This treatment combines pembrolizumab, a drug that helps the immune system attack cancer by blocking a protein called PD-1, with VIR-5525, which may enhance this effect. Pembrolizumab is already used for various cancers, but combining it with VIR-5525 could potentially improve its effectiveness against solid tumors. ^{1 7 10 11 12}

Research Team

Clinical Sciences & Operations

Principal Investigator

Vir Biotechnology

Eligibility Criteria

This trial is for adults with advanced or widespread solid tumors that have a protein called EGFR. Participants should be able to perform daily activities mostly without help. They can't join if they've had certain treatments recently, are pregnant, have immune or lung problems, or infections.

Inclusion Criteria

Have a life expectancy of at least 12 weeks.

I am legally an adult and can consent to participate.

I am fully active or restricted in physically strenuous activity but can do light work.

Exclusion Criteria

Are a WOCBP with a positive serum or urine pregnancy test within 72 hours prior to treatment.

Have a QT interval corrected by Fridericia's method (QTcF) that is >480 ms.

I do not have any current or past serious infections like EBV, hepatitis, HIV, or COVID-19.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

Up to 4 weeks

Treatment - VIR-5525 Monotherapy Dose Escalation

Participants receive VIR-5525 as monotherapy in a dose-escalation format

21-day cycles, up to approximately 52 months

Treatment - VIR-5525 Monotherapy Dose Expansion

Participants receive VIR-5525 as monotherapy in a dose-expansion format

21-day cycles, up to approximately 52 months

Treatment - VIR-5525 + Pembrolizumab Dose Escalation

Participants receive VIR-5525 in combination with pembrolizumab in a dose-escalation format

21-day cycles, up to approximately 52 months

Treatment - VIR-5525 + Pembrolizumab Dose Expansion

Participants receive VIR-5525 in combination with pembrolizumab in a dose-expansion format

21-day cycles, up to approximately 52 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Pembrolizumab
• VIR-5525

Trial Overview The study tests VIR-5525 alone and combined with Pembrolizumab in escalating doses to find safe levels and see if they shrink tumors. It's split into four parts: two for each treatment on its own (dose finding and then more patients), followed by the same steps for the combination.

Participant Groups

Group I: Part 4: VIR-5525 Combination Dose Expansion Experimental Treatment 2 Interventions

Screening Period: Up to 28 days Treatment Period: Once successfully screened, enrolled participants may receive study intervention of VIR-5525 in combination with pembrolizumab.

Group II: Part 3: VIR-5525 Combination Dose Escalation Experimental Treatment 2 Interventions

Screening Period: Up to 28 days Treatment Period: Once successfully screened, enrolled participants may receive study intervention of VIR-5525 in combination with pembrolizumab.

Group III: Part 2: VIR-5525 Monotherapy Dose Expansion Experimental Treatment 1 Intervention

Screening Period: Up to 28 days Treatment Period: Once successfully screened, enrolled participants may receive study intervention of VIR-5525 in monotherapy.

Group IV: Part 1: VIR-5525 Monotherapy Dose Escalation Experimental Treatment 1 Intervention

Screening Period: Up to 28 days Treatment Period: Once successfully screened, enrolled participants may receive study intervention of VIR-5525 in monotherapy.

Who Is Running the Clinical Trial?

Vir Biotechnology, Inc.

Lead Sponsor

Trials

30

Recruited

13,300+

Findings from Research

Pembrolizumab is a monoclonal antibody that effectively blocks the PD-1 receptor on T cells, enhancing their ability to attack cancer cells, particularly in melanoma patients.

In a Phase I study involving 411 patients, pembrolizumab demonstrated high durable response rates with minimal toxicity, indicating its potential as a safe and effective treatment option for melanoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab joins the anti-PD-1 armamentarium in the treatment of melanoma. Hersey, P., Gowrishankar, K.[2017]

Pembrolizumab is a monoclonal antibody that blocks the PD-1/PD-L1 interaction, which is crucial for preventing the immune system from attacking tumors, making it a key player in cancer immunotherapy.

It has been approved by the FDA for treating patients with advanced melanoma who have not responded to previous treatments, highlighting its efficacy in managing difficult cases of this aggressive cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New developments in the management of advanced melanoma - role of pembrolizumab. Improta, G., Leone, I., Donia, M., et al.[2020]

In a randomized trial comparing FDA-approved immune checkpoint inhibitors for advanced melanoma, pembrolizumab showed significantly better treatment outcomes than ipilimumab.

This study is notable as it is the first to directly compare these two therapies as first-line treatments, highlighting pembrolizumab's potential as a more effective option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab superior to ipilimumab in melanoma. [2017]

In a study of 183 patients with advanced melanoma treated with pembrolizumab, several baseline factors such as active brain metastases, higher total metabolic tumor volume (TMTV), and lower absolute lymphocyte count (ALC) were linked to worse survival outcomes.

TMTV was identified as a more effective predictor of treatment futility compared to other markers like C-reactive protein (CRP) and lactate dehydrogenase (LDH), suggesting that patients with high TMTV may not benefit from pembrolizumab therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Comprehensive Analysis of Baseline Clinical Characteristics and Biomarkers Associated with Outcome in Advanced Melanoma Patients Treated with Pembrolizumab. Awada, G., Jansen, Y., Schwarze, JK., et al.[2021]

Pembrolizumab is a safe and effective immune checkpoint inhibitor that targets the PD-1 receptor, currently approved for treating advanced melanoma and metastatic non-small cell lung cancer (NSCLC).

Ongoing studies are exploring the potential of pembrolizumab in combination with other treatments for lung cancer and other cancer types, while also investigating biomarkers that may predict patient response to this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of PD-L1 positive advanced or metastatic non-small cell lung cancer. Dang, TO., Ogunniyi, A., Barbee, MS., et al.[2020]

Pembrolizumab, an anti-PD-1 antibody, has been approved for treating unresectable or metastatic melanoma, especially in patients who have progressed after ipilimumab treatment, marking a significant advancement in immuno-oncology.

The drug has also received breakthrough status for treating non-small cell lung cancer (NSCLC) that is EGFR mutation-negative and ALK rearrangement-negative, indicating its broad potential in cancer therapy, with ongoing trials to explore its use in various tumor types.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab. Khoja, L., Butler, MO., Kang, SP., 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, an anti-PD-1 antibody, has shown significant efficacy in treating advanced melanoma, demonstrating superior progression-free survival compared to chemotherapy in Phase II trials and improved overall survival in Phase III trials.

The treatment is generally well tolerated with a favorable safety profile, though common side effects include fatigue and rash, while less frequent but serious immune-related adverse events can occur.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab in the management of metastatic melanoma. Spain, L., Younger, E., Hatipoglu, E., et al.[2020]

Pembrolizumab is an effective monoclonal antibody that targets the PD-1 immune checkpoint, helping to restore T cell anti-tumor responses, and is administered at a dose of 200 mg every 3 weeks until disease progression or for up to 24 months.

It has received approval for treating various cancers, including melanomas and non-small cell lung cancers, particularly in tumors that are hypermutated or express PD-L1, but ongoing research aims to expand its use to less immunogenic tumor types through combination therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical utility of pembrolizumab in the management of advanced solid tumors: an evidence-based review on the emerging new data. du Rusquec, P., de Calbiac, O., Robert, M., et al.[2023]

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 review of 567 reports of immune-mediated necrotizing myopathy (IMNM), 14 cases were associated with pembrolizumab, indicating a significant link between this treatment and the adverse event, with a reporting odds ratio of 17.59.

The study emphasizes the importance of updated diagnostic criteria for IMNM and suggests that better collaboration between oncologists and neurologists is needed to address these neurological complications related to pembrolizumab treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immune-mediated necrotizing myopathy with pembrolizumab: a specific neuromuscular entity. Trenque, T., Lepoix, E., Trenque, A., et al.[2022]

References

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

Pembrolizumab joins the anti-PD-1 armamentarium in the treatment of melanoma. [2017]

2. New Zealand pubmed.ncbi.nlm.nih.gov

New developments in the management of advanced melanoma - role of pembrolizumab. [2020]

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

Pembrolizumab superior to ipilimumab in melanoma. [2017]

4. Switzerland pubmed.ncbi.nlm.nih.gov

A Comprehensive Analysis of Baseline Clinical Characteristics and Biomarkers Associated with Outcome in Advanced Melanoma Patients Treated with Pembrolizumab. [2021]

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

Pembrolizumab for the treatment of PD-L1 positive advanced or metastatic non-small cell lung cancer. [2020]

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

Pembrolizumab. [2022]

7. 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]

8. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab-induced thrombotic thrombocytopenic purpura. [2022]

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

Pembrolizumab in the management of metastatic melanoma. [2020]

10. New Zealand pubmed.ncbi.nlm.nih.gov

Clinical utility of pembrolizumab in the management of advanced solid tumors: an evidence-based review on the emerging new data. [2023]

11. 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]

12. Germany pubmed.ncbi.nlm.nih.gov

Immune-mediated necrotizing myopathy with pembrolizumab: a specific neuromuscular entity. [2022]