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BRIEF TITLE: Investigate the Safety, Tolerability, Pharmacokinetics, Biological and Clinical Activity of Avelumab (MSB0010718C) in Subjects With Metastatic or Locally Advanced Solid Tumors and Expansion to Selected Indications

A Phase I, Open-label, Multiple-ascending Dose Trial to Investigate the Safety, Tolerability, Pharmacokinetics, Biological and Clinical Activity of Avelumab (MSB0010718C) in Subjects With Metastatic or Locally Advanced Solid Tumors and Expansion to Selected Indications


  • Org Study ID: EMR 100070-001
  • Secondary ID: 2013-002834-19
  • NCT ID: NCT01772004
  • NCT Alias:
  • Sponsor: EMD Serono - Industry
  • Source: EMD Serono

Brief Summary

This is a Phase 1, open-label, dose-escalation trial of avelumab [antibody targeting programmed death ligand 1 (anti PD-L1)] with consecutive parallel group expansion in subjects with selected tumor indications. New recruitment is open for all active cohorts. Active cohorts: Escalation revised dosing regimen cohort. Closed cohorts: Non-small cell lung cancer (NSCLC, first line), NSCLC (post-platinum), metastatic breast cancer (MBC), colorectal cancer (CRC), urothelial carcinoma (secondary), mesothelioma, gastric/GEJ cancer (first line switch maintenance and second line), and ovarian cancer (secondary and platinum refractory + liposomal doxorubicin), renal cell carcinoma (second line) melanoma and head, neck squamous cell carcinoma (HNSCC), castrate-resistant prostate cancer (CRPC), adrenocortical carcinoma (ACC) urothelial carcinoma (efficacy), gastric/gastroesophageal junction (GEJ) cancer (third line), renal cell carcinoma (RCC, first line) and escalation phase .

Overal Status Start Date Phase Study Type
Recruiting January 31, 2013 Phase 1 Interventional

Primary Outcomes:

Primary Outcome 1 - Measure: Dose Limiting Toxicity

Primary Outcome 1 - Time Frame: Up to 3 weeks

Primary Outcome 2 - Measure: Confirmed Best Overall Response (BOR) as per Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) for Efficacy Expansion Cohorts

Primary Outcome 2 - Time Frame: Every 6 weeks for first 12 months, then 12-weekly until end of treatment and post treatment every 3 months ( up to 52 months)

Condition:

  • Solid Tumors

Eligibility

Criteria:
Inclusion Criteria for dose escalation and expansion phase:

- Signed written informed consent

- Male or female subjects aged greater than or equal to 18 years

- Subjects must have histologically or cytologically proven metastatic or locally
advanced solid tumors, for which no standard therapy exists or standard therapy has
failed. Availability of tumor archival material or fresh biopsies is optional for
subjects in dose escalation

- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 at trial entry
and an estimated life expectancy of at least 3 months

- Disease must be measurable with at least 1 uni-dimensional measurable lesion by RECIST
1.1, except for subjects with metastatic castrate-resistant prostate cancer (mCRPC) or
metastatic breast cancer (MBC) who may be enrolled with objective evidence of disease
without a measureable lesion

- Adequate hematological, hepatic and renal function as defined in the protocol

- Effective contraception for both male and female subjects if the risk of conception
exists

- Other protocol defined inclusion criteria could apply

Inclusion Criteria for expansion phase:

- Subjects must have relapsed, refractory, or progressive disease following last line of
treatment (with the exception of the gastric and gastroesophageal junction (GEJ)
cancer cohort, which does not require progression). Availability of tumor archival
material or fresh biopsies (excluding bone biopsies) is mandatory for eligibility in
the expansion cohorts. For subjects in the MBC cohort, the biopsy or surgical specimen
must have been collected within 90 days prior to the first investigational medicinal
product (IMP) administration. Specifically, the following will be required:

- NSCLC post platinum doublet: Histologically or cytologically confirmed stage IIIB or
stage IV NSCLC that has progressed after 1 line of platinum-containing doublet
chemotherapy. Subjects should have received only 1 line of platinum-containing
treatment for metastatic disease (i.e., adjuvant treatment with a platinum-containing
regimen is not sufficient for eligibility because not received in the context of a
metastatic disease). Subjects in the NSCLC cohort will only be enrolled in USA

- NSCLC first line: Stage IV (per 7th International Association for the Study of Lung
Cancer [IASLC] classification) or recurrent NSCLC that is histologically proven.
Subjects must not have received treatment for their metastatic or recurrent disease.
No activating epidermal growth factor receptor (EGFR) mutation nor ALK
translocation/re-arrangement

- Gastric and GEJ cancer: Histologically confirmed, unresectable locally advanced or
metastatic adenocarcinoma of the gastric and gastro-esophageal junction, treated with
first-line chemotherapy combination with or without disease progression. Subjects
should have received no more than 1 line of treatment for metastatic disease. Subjects
should not have been treated with trastuzumab (but can be Human Epidermal growth
factor Receptor 2 [HER2] positive). Subjects who received any platinum containing
doublet or triplet as a neoadjuvant chemotherapy strategy, but are not ultimately
candidates for surgery will also be eligible, as long as they did not have progressive
disease after completion of the neoadjuvant chemotherapy. In addition, subjects with
gastric cancer can enter in the study if their white blood cell (WBC) and lymphocyte
count is as defined in the protocol

- MBC: Subjects must have histologically confirmed locally advanced or MBC and have
tumor that is refractory to or progressive after standard of care therapy. Subjects
must have received no more than 3 prior lines of cytotoxic therapy for metastatic
disease. Subjects must have received a taxane and an anthracycline, unless
contra-indicated

- Secondary expansion cohorts: Metastatic colorectal cancer (mCRC), Metastatic
castrate-resistant prostate cancer (mCRPC), melanoma, ovarian cancer, ACC,
mesothelioma, urothelial carcinoma and renal cell carcinoma as defined in the protocol

- Efficacy expansion cohorts: Gastric and GEJ cancer (third line), ovarian cancer
(platinum Refractory + liposomal doxorubicin), urothelial carcinoma, and HNSCC as
defined in the protocol

- Other protocol defined inclusion criteria for expansion phase could apply

Exclusion Criteria for dose escalation and expansion phase:

- Concurrent treatment with a non-permitted drug

- Prior therapy with specific antibody/drug targeting T cell co-regulatory proteins
(immune checkpoints)

- Concurrent anticancer treatment, major surgery, or use of any investigational drug
within 28 days before the start of trial treatment; or concurrent systemic therapy
with immunosuppressive agents, use of hormonal agents within 7 days before the start
of trial treatment as defined in the protocol. Note: Subjects receiving bisphosphonate
or denosumab are eligible provided treatment was initiated at least 14 days before the
first dose of avelumab.

- Previous malignant disease other than the target malignancy to be investigated in this
trial within the last 5 years with the exception of basal or squamous cell carcinoma
of the skin or cervical carcinoma in situ

- Rapidly progressive disease (for example, tumor lysis syndrome)

- Active or history of central nervous system metastases

- Receipt of any organ transplantation including allogeneic stem-cell transplantation

- Significant acute or chronic infections as defined in the protocol

- Active or history of any autoimmune disease (subjects with diabetes Type 1, vitiligo,
psoriasis, hypo- or hyperthyroid disease not requiring immunosuppressive treatment are
eligible) or immunodeficiencies

- Known severe hypersensitivity reactions to monoclonal antibodies, any history of
anaphylaxis, or uncontrolled asthma

- Persisting toxicity related to prior therapy greater than Grade 1 NCI-CTCAE v4.0,
however sensory neuropathy less than or equal to Grade 2 is acceptable

- Pregnancy or lactation period

- Known alcohol or drug abuse

- Clinically significant (that is, active) cardiovascular disease

- All other significant diseases (for example, inflammatory bowel disease), which, in
the opinion of the investigator, might impair the subject's tolerance of trial
treatment

- Any psychiatric condition that would prohibit the understanding or rendering of
informed consent

- Legal incapacity or limited legal capacity

- Non-oncology vaccine therapies for prevention of infection disease (for example,
seasonal flu vaccine, human papilloma virus vaccine) within 4 weeks of study drug
administration. Vaccination while on study is also prohibited except for
administration of the inactivated influenza vaccine
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Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

Official Information

Name: Medical Responsible

Role: Study Director

Affiliation: EMD Serono Inc., an affiliate of Merck KGaA, Darmstadt, Germany

Overall Contact

Name: US Medical Information

Phone: 888-275-7376

Email:

Locations

Facility Status Contact
For Recruiting Locations in the United States, please Contact U.S. Medical Information
Rockland, Massachusetts
United States
Recruiting
888-275-7376
Please contact the Merck KGaA Communication Center
Leuven,
Belgium
Active, not recruiting
Please contact the Merck KGaA Communication Center
Praha,
Czechia
Active, not recruiting
Please contact the Merck KGaA Communication Center
Paris,
France
Active, not recruiting
Please contact the Merck KGaA Communication Center
Berlin,
Germany
Active, not recruiting
Please contact the Merck KGaA Communication Center
Budapest,
Hungary
Active, not recruiting
Please contact the Merck KGaA Communication Center
Seoul,
Korea, Republic of
Active, not recruiting
Please contact the Merck KGaA Communication Center
Warszawa,
Poland
Active, not recruiting
Please contact the Merck KGaA Communication Center
Taipei,
Taiwan
Active, not recruiting
Please contact the Merck KGaA Communication Center
London,
United Kingdom
Active, not recruiting