Continued Avelumab-Based Therapy for Cancer

Recruiting at 72 trial locations

Overseen By Pfizer CT.gov Call Center

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Pfizer

Must be taking: Avelumab

Disqualifiers: Pregnancy, Breastfeeding, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

67 Participants Needed

Trial Summary

What is the purpose of this trial?

This Master Protocol for Avelumab Continuation Sub-Studies is to provide continued treatment access, safety follow-up, and when applicable, overall survival follow-up for eligible participants who continue to derive a benefit from study intervention in the Pfizer-sponsored Avelumab parent studies.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the study team or your doctor.

What data supports the effectiveness of the drug Avelumab?

Avelumab has been shown to be effective in treating certain types of cancer, such as metastatic Merkel cell carcinoma and advanced urothelial carcinoma, by blocking a protein that helps cancer cells hide from the immune system. It has been approved by the FDA for these uses and has demonstrated the ability to prolong survival in patients with these cancers. ^{1 2 3 4 5}

Is Avelumab safe for human use?

Avelumab, also known as Bavencio, has been shown to have an acceptable safety profile in patients with advanced solid tumors, including metastatic Merkel cell carcinoma and non-small-cell lung cancer. Some patients may experience immune-related side effects, but these are often manageable and associated with improved outcomes. ^{2 3 4 5 6}

How is the drug Avelumab unique compared to other cancer treatments?

Avelumab is unique because it is a monoclonal antibody that targets PD-L1, a protein on tumor cells, to prevent it from interacting with PD-1 on T cells, which helps the immune system attack the cancer. This mechanism of action is different from traditional chemotherapy, as it specifically enhances the body's immune response against tumors. ^{1 2 5 7 8}

Research Team

Pfizer CT.gov Call Center

Principal Investigator

Pfizer

Eligibility Criteria

This trial is for patients benefiting from Avelumab in previous Pfizer studies, who have solid tumors or specific cancers like lung, bladder, or ovarian cancer. They must follow reproductive guidelines and be able to stick with the study plan. Pregnant or breastfeeding women can't participate.

Inclusion Criteria

Participants must agree to follow the reproductive criteria.

Participants must be willing and able to comply with all scheduled visits, treatment plan, and other study procedures.

Any participant who is receiving study treatment and deriving significant clinical benefit or is in the safety and/or survival follow-up period in a Pfizer-sponsored Avelumab Parent Study.

Exclusion Criteria

I am not pregnant or breastfeeding.

Any medical reason that, in the opinion of the Investigator or Sponsor, precludes the participant from inclusion in the study.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants continue to receive Avelumab treatment as per their respective sub-study protocols

Safety Follow-up

Participants are monitored for safety after continuing treatment

4 weeks

Overall Survival Follow-up

Participants are monitored for overall survival outcomes

Treatment Details

Interventions

• Avelumab
• Continued Access Study

Trial Overview The trial continues access to treatments such as Pemetrexed and Avelumab for those already seeing benefits. It also includes safety monitoring and survival tracking for various drugs that were part of earlier Avelumab studies.

Participant Groups

Group I: Arm 8 Experimental Treatment 2 Interventions

Avelumab in combination with Talazoparib as specified by sub-study B9991032C.

Group II: Arm 7 Experimental Treatment 2 Interventions

Avelumab in combination with Axitinib as specified by sub-study B9991027C.

Group III: Arm 6 Experimental Treatment 2 Interventions

Avelumab in combination with Talazoparib as specified by sub-study B9991025C.

Group IV: Arm 5 Experimental Treatment 2 Interventions

Avelumab monotherapy or in combination with Pemetrexed as specified by sub-study protocol B9991023C

Group V: Arm 4 Experimental Treatment 1 Intervention

Avelumab monotherapy as specified by sub-study protocol B9991009C

Group VI: Arm 3 Experimental Treatment 2 Interventions

Avelumab in combination with Loratanib as specified by sub-study protocol B9991005C

Group VII: Arm 2 Experimental Treatment 4 Interventions

Avelumab in combination with CMP 001, Utomilumab or PF04518600 as specified by sub-study protocol B9991004C

Group VIII: Arm 1 Experimental Treatment 1 Intervention

Avelumab monotherapy as specified by sub-study protocol B9991001C

Avelumab is already approved in European Union, United States, Japan for the following indications:

Approved in European Union as Bavencio for:

• Merkel cell carcinoma
• Renal cell carcinoma
• Urothelial carcinoma

Approved in United States as Bavencio for:

• Merkel cell carcinoma
• Renal cell carcinoma
• Urothelial carcinoma

Approved in Japan as Bavencio for:

• Merkel cell carcinoma
• Renal cell carcinoma
• Urothelial carcinoma

Who Is Running the Clinical Trial?

Pfizer

Lead Sponsor

Trials

4,712

Recruited

50,980,000+

Known For

Vaccine Innovations

Top Products

Viagra, Zoloft, Lipitor, Prevnar 13

Albert Bourla

Pfizer

Chief Executive Officer since 2019

PhD in Biotechnology of Reproduction, Aristotle University of Thessaloniki

Patrizia Cavazzoni

Pfizer

Chief Medical Officer

MD from McGill University

Findings from Research

Avelumab, a monoclonal antibody targeting PD-L1, demonstrated an acceptable safety profile in a phase 1a trial with 53 patients, with only one dose-limiting toxicity observed at the highest dose of 20 mg/kg, indicating that the maximum tolerated dose was not reached.

The pharmacokinetic analysis showed a dose-proportional exposure and a half-life of approximately 4 days at higher doses, leading to the selection of 10 mg/kg every 2 weeks for further development, as it achieved over 90% target occupancy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Avelumab for metastatic or locally advanced previously treated solid tumours (JAVELIN Solid Tumor): a phase 1a, multicohort, dose-escalation trial. Heery, CR., O'Sullivan-Coyne, G., Madan, RA., et al.[2022]

Avelumab is an antibody that blocks programmed cell death ligand-1 (PD-L1) and has received accelerated approval in the USA for treating metastatic Merkel cell carcinoma (mMCC) in both adults and children aged 12 and older.

The drug is also undergoing regulatory reviews for other cancer treatments, including urothelial carcinoma, indicating its potential as a versatile cancer therapy in various stages of development worldwide.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Avelumab: First Global Approval. Kim, ES.[2022]

Avelumab maintenance therapy after platinum-based chemotherapy in advanced urothelial carcinoma significantly improves overall response rate (ORR), progression-free survival (PFS), and overall survival (OS), especially in patients with PD-L1 positive tumors, compared to those receiving best supportive care.

While avelumab is effective, it is associated with a high rate of treatment-related adverse events (TRAEs) in 86.7% of patients, with 32.4% experiencing severe adverse events, indicating the need for careful patient monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Evaluation of Avelumab in the Treatment of Advanced Urothelial Carcinoma: Focus on Patient Selection and Outcomes. Ten Eyck, JE., Kahlon, N., Masih, S., et al.[2022]

In a study of 204 patients with advanced urothelial carcinoma, those receiving maintenance avelumab therapy showed longer overall survival compared to those receiving second-line pembrolizumab or cytotoxic chemotherapy, although progression-free survival was not significantly different.

Patients who started maintenance avelumab therapy within 6 weeks of completing first-line chemotherapy had a higher disease control rate (77%) compared to those who waited longer, suggesting that early initiation of avelumab may enhance treatment effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Switch-maintenance avelumab immunotherapy following first-line chemotherapy for patients with advanced, unresectable or metastatic urothelial carcinoma: the first Japanese real-world evidence from a multicenter study. Miyake, M., Shimizu, T., Oda, Y., et al.[2023]

In a phase 1/2 trial involving 40 patients with recurrent gynecologic cancers, the combination of avelumab and utomilumab was found to be safe, with no serious immune-related adverse events reported.

The objective response rate (ORR) was low at 2.9% overall, but patients with cervical cancer showed a promising ORR of 11% and a disease control rate (DCR) of 78%, suggesting potential for further investigation in this subgroup.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1/2 trial of avelumab combined with utomilumab (4-1BB agonist), PF-04518600 (OX40 agonist), or radiotherapy in patients with advanced gynecologic malignancies. Knisely, A., Ahmed, J., Stephen, B., et al.[2023]

References

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

Product review: avelumab, an anti-PD-L1 antibody. [2020]

2. England pubmed.ncbi.nlm.nih.gov

Avelumab for metastatic or locally advanced previously treated solid tumours (JAVELIN Solid Tumor): a phase 1a, multicohort, dose-escalation trial. [2022]

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

Avelumab: First Global Approval. [2022]

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

Clinical Evaluation of Avelumab in the Treatment of Advanced Urothelial Carcinoma: Focus on Patient Selection and Outcomes. [2022]

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

Avelumab for patients with previously treated metastatic or recurrent non-small-cell lung cancer (JAVELIN Solid Tumor): dose-expansion cohort of a multicentre, open-label, phase 1b trial. [2022]

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

Efficacy and immune-related adverse event associations in avelumab-treated patients. [2021]

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

Switch-maintenance avelumab immunotherapy following first-line chemotherapy for patients with advanced, unresectable or metastatic urothelial carcinoma: the first Japanese real-world evidence from a multicenter study. [2023]

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

Phase 1/2 trial of avelumab combined with utomilumab (4-1BB agonist), PF-04518600 (OX40 agonist), or radiotherapy in patients with advanced gynecologic malignancies. [2023]