Phase 1B/2 study of avelumab in patients with advanced malignancies
Research type
Research Study
Full title
A phase 1b/2 open-label study to evaluate safety, clinical activity, pharmacokinetics and pharmacodynamics of avelumab* (MSB0010718C) in combination with other cancer immunotherapies in patients with advances malignancies
IRAS ID
184651
Contact name
James Larkin
Contact email
Sponsor organisation
Pfizer Inc, 235 East 42nd Street, New York, NY 10017
Eudract number
2015-002552-27
Duration of Study in the UK
1 years, 9 months, 12 days
Research summary
Research Summary:
Avelumab and PF-05082566 are new cancer immunotherapies (a type of protein) thought to help the immune system to fight against cancer cells. Avelumab and PF-05082566 have been previously tested on their own in animals and patients. The combination of avelumab and PF-05082566 has not be tested in humans but it is thought that giving both drugs together may work better at treating solid tumours than giving only one drug by itself.This clinical trial will determine the anticancer activity, safety and effectiveness of avelumab in combination with three different doses of PF-05082566 in patients with solid tumours that have advanced or spread to other parts of the body.
18 participants with non-small cell lung cancer will take part in the first phase and will be assigned at random to receive avelumab and one of three doses of PF-05082566. A further 22 participants for each dose that is tolerated in the first phase will be recruited in the second phase. Additionally in the second phase participants with melanoma and squamous cell carcinoma of the head and neck will be enrolled to receive aveulmab in combination with one dose level PF-05082566. Approximately 147 participants will take part in the study. The UK will be taking part in the second phase only.
Participants will receive their allocated treatment in 28-day cycles until their disease worsens, they experience unacceptable side effects, the participant withdraws or the study is terminated.
Participants will attend study visits at screening, weekly during study treatment, at end of treatment, 30, 60 and 90 day follow up, followed by telephone calls every 3 months. The participant’s duration in the study will depend on the number of treatment cycles. Study procedures include physical examinations, ECGs, blood tests, urine tests, biopsies, CT/MRI scans and bone scans if required.
Pfizer, Inc. is the sponsor.
Summary of ResultsEfficacy Conclusion:
- Limited objective response was noted across Cohorts in each combination. The objective responses observed did not warrant further investigation into or beyond Phase 2.
Safety Conclusions:
- There were no DLTs in Combinations A, B and C. The numbers of participants with DLTs were low in Combinations D and F.
- The AE profiles were similar across different cohorts and combinations with no increased rates of irAEs in combinations of 2 or 3 immunotherapies in relation to the previously described profile for avelumab monotherapy.
- There were no irAEs leading to death in any of the combinations.
- Cytokine release syndrome was reported only in combination F which includes CMP-001 that has a known risk for this AE.
- There were no other clinically significant findings of safety concerns in any of the combinations.
PK Conclusion:
- Co-administration of avelumab 10 mg/kg Q2W with utomilumab (Combination A), PF-04518600 (Combination B), PD 0360324 (Combination C), utomilumab and PF-04518600 (Combination D), and CMP-001 with or without utomilumab or PF-04518600 (Combination F) resulted in no clinically meaningful effect on the exposure of avelumab, utomilumab, PF-04518600 or PD 0360324.
Biomarkers Conclusion:
- No conclusions can be drawn due to the small size of the biomarker cohorts.
Immunogenicity Conclusion:
- The observed incidences of avelumab treatment-induced ADA response ranged between 0% (Combination B) and 8.6% (Combination A), which were comparable to other avelumab studies.
:REC name
South Central - Oxford B Research Ethics Committee
REC reference
16/SC/0139
Date of REC Opinion
14 Apr 2016
REC opinion
Further Information Favourable Opinion