Continued Avelumab-Based Therapy for Cancer

Not currently recruiting at 96 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the continued use of Avelumab (also known as MSB0010718C or Bavencio), alone or with other medications, for cancer patients who have benefited from it in previous studies. The goal is to provide ongoing access to potentially effective treatments while monitoring safety and survival. This trial suits those currently on Avelumab from earlier studies and experiencing positive results. Participants must attend regular check-ups and follow the treatment plan outlined by the study. As a Phase 3 trial, this represents the final step before FDA approval, offering participants access to a promising treatment option.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that Avelumab, whether used alone or with other drugs, generally has a manageable safety profile. In studies with patients who have advanced solid tumors, most side effects of Avelumab alone were mild and manageable. Common side effects included tiredness and muscle pain, while serious reactions were rare.

Real-world studies indicate that combining Avelumab with Axitinib is safe for patients with kidney cancer and is generally well-tolerated without unusual safety issues.

For the Avelumab-Loratanib combination, specific data is limited, but Avelumab alone is generally well-tolerated.

The Avelumab-Talazoparib combination also appears safe and well-tolerated based on studies with patients who have advanced solid tumors.

The safety of combinations with CMP 001, Utomilumab, or PF04518600 is still under investigation, but early results suggest they are tolerable.

For combinations with Pemetrexed, studies show Avelumab is generally safe when used with this chemotherapy drug, maintaining a safety profile similar to when used alone.

Overall, research suggests these treatments are usually well-tolerated, but individual experiences may vary. Always discuss potential risks and benefits with a healthcare provider. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Avelumab-based therapies because they offer a fresh approach to treating cancer. Unlike standard treatments like chemotherapy, which broadly target rapidly dividing cells, Avelumab is an immunotherapy that enhances the body's immune response against cancer cells. This study explores Avelumab both as a solo treatment and in combination with other drugs like Axitinib, Loratanib, and Talazoparib, which could potentially improve effectiveness by targeting multiple pathways in cancer development. These combinations aim to boost treatment efficacy and potentially reduce side effects compared to traditional therapies. Overall, this trial could open new doors in personalized cancer treatment, offering hope for better patient outcomes.

What evidence suggests that this trial's treatments could be effective?

Research has shown that avelumab, one of the treatments in this trial, holds promise for treating various cancers, whether used alone or with other drugs. In this trial, some participants will receive avelumab monotherapy, which has led to more tumor shrinkage compared to standard treatments, with about 14% of patients responding. Other participants will receive avelumab combined with axitinib, which resulted in 82.7% of patients with advanced kidney cancer surviving for at least a year, a very encouraging outcome. The combination with lorlatinib, another treatment arm in this trial, showed a 46% response rate in patients with ALK-positive non-small cell lung cancer. Avelumab with talazoparib, also being studied in this trial, was especially effective for patients with BRCA gene changes, showing a 70% response rate. Other combinations, such as with CMP 001 and pemetrexed, are also being explored in this trial and have shown early positive results, though more research is needed. ^{6 7 8 9 10}

Who Is on the Research Team?

Pfizer CT.gov Call Center

Principal Investigator

Pfizer

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

Group I: Arm 9 Experimental Treatment 2 Interventions

Avelumab in combination with Axitinib as specified by sub-study protocol B9991003C

Group II: Arm 8 Experimental Treatment 2 Interventions

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

Group III: Arm 7 Experimental Treatment 2 Interventions

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

Group IV: Arm 6 Experimental Treatment 2 Interventions

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

Group V: Arm 5 Experimental Treatment 2 Interventions

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

Group VI: Arm 4 Experimental Treatment 1 Intervention

Avelumab monotherapy as specified by sub-study protocol B9991009C

Group VII: Arm 3 Experimental Treatment 2 Interventions

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

Group VIII: Arm 2 Experimental Treatment 4 Interventions

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

Group IX: 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

Published Research Related to This Trial

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]

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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12025360/

Real-World Clinical Outcomes with First-Line Systemic ... Patients with locally advanced or metastatic urothelial cancer (la/mUC) have poor prognosis, with an estimated 5-year survival rate of 8.8% [2].

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1040842821002511

Efficacy and safety profile of avelumab monotherapy Compared with conventional treatment, avelumab monotherapy was associated with more tumor responses and less AEs. The pooled objective response rate was 14.18 % ...

3. bavencio.com bavencio.com/en_US/patients-and-caregivers/mcc-home/clinical-study-results.html

Clinical Study Results | BAVENCIO® (avelumab) Efficacy Efficacy of BAVENCIO® (avelumab) in clinical studies. See how effective BAVENCIO® (avelumab) is for patients with Merkel cell carcinoma.

4. nejm.org nejm.org/doi/full/10.1056/NEJMoa2002788

Avelumab Maintenance Therapy for Advanced or ... In patients with PD-L1–negative tumors, the median progression-free survival was 3.0 months (95% CI, 2.0 to 3.7) in the avelumab group and 1.9 ...

5. emdserono.com emdserono.com/us-en/company/news/press-releases/european-commission-approves-bavencio-r-avelumab-for-first-line-maintenance-treatment-02-01-2021.html

European Commission Approves BAVENCIO® (avelumab ... BAVENCIO maintenance treatment significantly extended median overall survival versus standard of care in the Phase III JAVELIN Bladder 100 ...

6. bavencio.com bavencio.com/en_US/hcp/mcc-home/safety-profile.html

Merkel Cell Carcinoma Safety Profile Find the BAVENCIO® (avelumab) safety profile, including adverse reactions & dose modifications for metastatic Merkel cell carcinoma.

7. ascopubs.org ascopubs.org/doi/10.1200/JCO.2016.34.15_suppl.3055

Avelumab (MSB0010718C; anti-PD-L1) in patients with ... Conclusions: Single-agent avelumab showed an acceptable safety profile in a heavily pretreated population and large dataset of pts with LA/M ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5947549/

Safety profile of avelumab in patients with advanced solid ... Avelumab generally was found to be well tolerated and to have a manageable safety profile. A minority of patients experienced grade ≥3 TRAEs or irAEs, and ...

9. bavencio.com bavencio.com/en_US/hcp.html

BAVENCIO® (avelumab) For Healthcare Professionals The most common adverse reactions (all grades, ≥20%) in patients with metastatic Merkel cell carcinoma (MCC) were fatigue (47%), musculoskeletal pain (29%), ...

10. fda.gov fda.gov/drugs/resources-information-approved-drugs/avelumab-bavencio

Avelumab (BAVENCIO) Safety data were evaluated in 1738 patients who received avelumab, 10 mg/kg, every 2 weeks. The most common serious adverse reactions to ...