A Study Of Avelumab In Combination With Other Cancer Immunotherapies In Advanced Malignancies (JAVELIN Medley)
- Conditions
- ocally advanced or metastatic solid tumors [eg, non-small cell lung cancer (NSCLC), melanoma, and squamous cell carcinoma of the head and neck (SCCHN)] triple-negative breast cancer (TNBC), or colorectal cancer (CRC)].MedDRA version: 19.0Level: LLTClassification code 10048683Term: Advanced cancerSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2015-002552-27-NL
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 549
1. Histological or cytological diagnosis of advanced/metastatic solid tumor as follows
Measurable disease by RECIST v1.1 with at least 1 measurable lesion that has not previously been irradiated.
Availability of tumor specimens: For Phase 1b: Archival formalin-fixed paraffin-embedded (FFPE) tissue is required if available for the first 3 patients enrolled in a cohort. For Phase 2 and additional patients enrolled beyond the first 3 in a Phase 1b cohort: FFPE tissue must be available from the most recent primary or metastatic tumor biopsy or resection prior to start of study therapy, taken within 1 year prior to study entry, with no intervening systemic anti-cancer therapy. HPV status based on locally approved testing for patients with SCCHN, and MSI status based on locally approved testing for patients with CRC.
Patients with a history of PD-1 or PD-L1 inhibitor refractory disease (best response of PD) are not eligible.
Combo A- 1b: NSCLC that has progressed on standard therapy or for which no standard therapy is available.
Phase 2:
NSCLC, melanoma, or SCCHN in any line of therapy;
NSCLC patients with tumor ALK translocations or EGFR mutations must have received, or been refractory/intolerant to, standard therapy.
TNBC that has progressed after 1 line of therapy or is ineligible for/intolerant to SOC; or
SCLC that has progressed after at least 1 line of platinum-containing therapy or is ineligible for/intolerant to SOC.
NSCLC first-line Stage IV or recurrent NSCLC that is histologically proven. Patients must not have received treatment for their metastatic or recurrent disease. Neither activating EGFR mutation nor ALK translocation/rearrangement are permitted (non-squamous cell histologies require testing if status is unknown). Patients could have received adjuvant chemotherapy or locoregional treatment that included chemotherapy for locally advanced disease as long as disease treatment occurred at least 6 months prior to study entry.
Combo B- 1b:
NSCLC, melanoma, or SCCHN that has progressed after at least 1 line of standard therapy or is ineligible for/intolerant to SOC.
Phase 2:
NSCLC, melanoma, SCCHN, or microsatellite instability-high (MSIhigh) CRC in any line of therapy; or
MSS CRC that has progressed after at least 2 lines of standard therapy or is ineligible for/intolerant to SOC.
NSCLC patients with tumor ALK translocations or EGFR mutations must have received, or been refractory/intolerant to, standard therapy.
Combo C- 1b:
Ovarian cancer, SCCHN, NSCLC, or gastric cancer, that has progressed after at least 1 line of standard therapy or is ineligible for/intolerant to SOC.
MSIhigh CRC in any line of therapy;
Phase 2 (up to 2 of the following tumor types will communicated by PACL):
NSCLC, SCCHN, or MSIhigh CRC in any line of therapy;
Ovarian cancer or gastric cancer that has progressed after at least 1 line of therapy or is ineligible for/intolerant to SOC; or
MSS CRC that has progressed after at least 2 lines of standard therapy or is ineligible for/intolerant to SOC.
NSCLC patients with tumor ALK translocations or EGFR mutations must have received or been refractory/intolerant to standard therapy.
Combo D-1b:
NSCLC, melanoma, or SCCHN that has progressed after at least 1 line of standard therapy or is ineligible for/intolerant to SOC;
MSIhigh CRC in any line of therapy;
Bladder cancer that has progressed after at least 1 line of standard therapy or is ineligible for/intolerant to SOC.
Phase 2 (up to 2 of the following tumor
Patients with any of the following characteristics/conditions will not be included in the study:
1. Monoclonal antibody based anti-cancer therapy within 28 days prior to study entry or small-molecule based anti-cancer therapy (targeted therapy or chemotherapy) within 14 days prior to study entry.
2. Current use of immunosuppressive medication at time of randomization. Please refer to the protcol for exceptions to this criteria.
3. Active autoimmune disease that might deteriorate when receiving an immunostimulatory agent. Please refer to the protcol for exceptions to this criteria.
4. Known prior or suspected hypersensitivity to investigational products or any component in their formulations, including known severe hypersensitivity reactions to mAbs (NCI CTCAE v4.03 Grade =3).
5. Major surgery within 4 weeks or radiation therapy within 14 days prior to study entry. Prior palliative radiotherapy to metastatic lesion(s) is permitted, provided it has been completed 48 hours prior to study entry and there is at least 1 measurable lesion that has not been irradiated.
6. Patients with known symptomatic brain metastases requiring steroids. Patients with previously diagnosed brain metastases are eligible if they have completed their treatment and have recovered from the acute effects of radiation therapy or surgery prior to study entry, have discontinued corticosteroid treatment for these metastases for at least 4 weeks prior to study entry, and are neurologically stable.
7. Previous high-dose chemotherapy requiring stem cell rescue.
8. Prior allogeneic stem cell transplant or organ graft.
9. Clinically significant (ie, active) cardiovascular disease: cerebral vascular accident/stroke (<6 months prior to enrollment), myocardial infarction (<6 months prior to enrollment), unstable angina, congestive heart failure (New York Heart Association Class =II), or serious cardiac arrhythmia requiring medication.
10. Symptomatic pulmonary embolism within 6 months prior to study entry.
11. Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS) related illness.
12. Existing periorbital edema.
13. Hypocalcemia (serum albumin adjusted calcium <7.5 mg/dL), clinically significant bone disease that may affect safe study participation at the discretion of the investigator, or recent bone fracture (within 12 weeks prior to study entry).
14. Active infection requiring systemic therapy.
15. Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection at screening (positive HBV surface antigen or HCV RNA if anti-HCV antibody screening tests positive).
16. Vaccination within 4 weeks of the first dose of investigational product and while on trial is prohibited except for administration of inactivated vaccines (for example, inactivated influenza vaccines).
17. Diagnosis of any other malignancy within 2 years prior to study entry, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ of the breast or of the cervix, or low-grade (Gleason =6) prostate cancer on surveillance with no plans for treatment intervention (eg, surgery, radiation or castration).
18. Patients who are investigational site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the investigator, or patients who are Pfizer employees directly involved in the conduct of the study.
19. Participation in other studies involving in
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method