A Study Of Avelumab In Combination With Other Cancer Immunotherapies In Advanced Malignancies (JAVELIN Medley)

Study ID
STU 022016-032

Study Sites

  • Clements University Hospital

Contact
Joyce Bolluyt
214/648-7007
joyce.bolluyt@utsouthwestern.edu

Principal Investigator
Saad Khan, M.D.

Official 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 Advanced Malignancies

Brief Overview

This is a Phase 1b/2 dose-optimization study to evaluate safety, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of avelumab (MSB0010718C) in combination with other cancer immunotherapies in patients with locally advanced or metastatic solid tumors. The primary purpose is to assess the safety and early signs of efficacy of various avelumab combinations with other cancer immunotherapies, optimizing dosing regimens as appropriate, in a limited series of indications.

Description

This is a Phase 1b/2, open-label, multi-center, multiple-dose, safety, clinical activity, PK, and PD study of avelumab in combination with other immune modulators in adult patients with locally advanced or metastatic solid tumors (eg, non-small cell lung cancer (NSCLC), melanoma, squamous cell carcinoma of the head and neck (SCCHN), triple-negative breast cancer (TNBC), colorectal cancer (CRC), gastric cancer, ovarian cancer, bladder cancer, or small cell lung cancer (SCLC)). In Phase 1b, this includes patients whose disease has progressed on standard of care therapy or for whom no standard therapy is available. In Phase 2, enrollment criteria regarding prior treatment(s) received varies by tumor type. Incorporation of the other immune modulators into this study is based on preclinical and clinical data supportive of single-agent tolerability and potential clinical benefit, as well as non-clinical data suggesting safety, tolerability and clinical benefit of the agent(s) in combination with avelumab. Combinations of avelumab plus other immune modulator(s) to be evaluated are as follows:
- Combination A: avelumab plus utomilumab (4-1BB agonist mAb)
- Combination B: avelumab plus PF-04518600 (OX40 agonist mAb)
- Combination C: avelumab plus PD 0360324 (M-CSF mAb)
- Combination D: avelumab plus utomilumab plus PF-04518600 Each combination will be studied individually in 2 study parts: 1) a Phase 1b Lead-in part to evaluate safety, and determine the maximum tolerated dose (MTD) or maximum administered dose (MAD) and RP2D (if applicable), of the combination, and 2) a Phase 2 part to evaluate efficacy and further evaluate safety of the selected dose from the Phase 1b portion in pre-specified patient populations.

Eligibility

Inclusion Criteria:
- Histological or cytological diagnosis of advanced/metastatic solid tumor. Combination A: Phase 1b, patients with NSCLC that have progressed on standard therapy or for which no standard therapy is available, and Phase 2, patients with NSCLC, melanoma, SCCHN, TNBC in any line of therapy, SCLC, 1st line NSCLC. Combination B: Phase 1b, patients with advanced solid tumors that have progressed on standard therapy or for which no standard therapy is available, and Phase 2, patients with NSCLC, melanoma, or SCCHN in any line of therapy, or locally advanced/metastatic CRC progressed after 1 line of standard therapy. NSCLC patients in Phase 2 with tumor ALK or EGFR mutations must have received or been refractory/intolerant to standard therapy. Combination C: 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. Combination D: NSCLC, melanoma, or SCCHN that has progressed after at least 1 line of standard therapy or is ineligible for/intolerant to SOC.
- ECOG performance status 0 or 1
- Estimated life expectancy of at least 3 months
- Adequate bone marrow, renal, and liver function
- Resolved acute effects of prior therapy
- Negative serum pregnancy test at screening
- Male and female patients able to have children must agree to use 2 highly effective methods of contraception throughout the study and for at least 60 days after last dose
- Signed and dated informed consent
Exclusion Criteria:
- 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.
- Current or prior use of immunosuppressive medication within 7 days prior to study entry
- Active autoimmune disease requiring systemic steroids or immunosuppressive agents within 7 days prior to study entry
- Known prior or suspected hypersensitivity to investigational products
- Major surgery within 4 weeks or radiation therapy within 14 days prior to study entry
- Patients with known symptomatic brain metastases requiring steroids
- Previous high-dose chemotherapy requiring stem cell rescue
- Prior allogeneic stem cell transplant or organ graft
- Any of the following within 6 months prior to study entry: myocardial infarction, uncontrolled angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident, or transient ischemic attack
- Symptomatic pulmonary embolism within 6 months prior to study entry
- Known HIV or AIDS-related illness
- Active infection requiring systemic therapy
- Positive HBV or HCV test indicating acute or chronic infection
- Administration of a live vaccine within 4 weeks prior to study entry
- Diagnosis of other malignancy within 5 years, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ of the breast or cervix, or low-grade (Gleason ≤6) prostate cancer
- Participation in other studies involving investigational drug(s) within 4 weeks prior to study entry and/or during study participation
- Persisting toxicity related to prior therapy >Grade 1
- Other severe acute or chronic medical condition