First-in-Human Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of IMGN853 in Adults With Ovarian Cancer and Other FOLR1-Positive Solid Tumors (IMGN-0401)

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by ImmunoGen, Inc.
Sponsor:
Information provided by (Responsible Party):
ImmunoGen, Inc.
ClinicalTrials.gov Identifier:
NCT01609556
First received: May 30, 2012
Last updated: June 26, 2014
Last verified: June 2014
  Purpose

The purpose of this study is to test IMGN853 in patients with FOLR-1 positive tumors every 21 days.


Condition Intervention Phase
FOLR-1 Positive Solid Tumors
Drug: IMGN853
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 1, First-in-Human Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of IMGN853 in Adults With Ovarian Cancer and Other FOLR1-Positive Solid Tumors

Resource links provided by NLM:


Further study details as provided by ImmunoGen, Inc.:

Primary Outcome Measures:
  • Determine Maximum Tolerated Dose and Recommended Phase II Dose of IMGN853 when administered intravenously every 3 weeks [ Time Frame: During study ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Evaluate the safety and tolerability of IMGN853 [ Time Frame: During the study ] [ Designated as safety issue: Yes ]
  • Characterize the PK of IMGN853 when administered intravenously every 3 weeks [ Time Frame: During the study ] [ Designated as safety issue: No ]
  • Assess IMGN853 PD activity via FLT-PET imaging (Expansion cohort #3, NSCLC only) and tumor biopsy (Expansion cohort #2, relapsed refractory EOC and #3 NSCLC only) pre and post dosing [ Time Frame: During the study ] [ Designated as safety issue: No ]
  • Characterize the immunogenicity of IMGN853 [ Time Frame: During the study ] [ Designated as safety issue: No ]
  • Describe any preliminary evidence of IMGN853 antitumor activity by estimation of objective response according to RECIST 1.1 and CA-125 response according to Gynecologic Cancer Intergroup (GCIG) criteria [ Time Frame: During the study ] [ Designated as safety issue: No ]

Estimated Enrollment: 64
Study Start Date: May 2012
Estimated Study Completion Date: March 2015
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: IMGN853
    Dose escalation study. Dosing on day 1 of every 21 day cycle.
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

1. Diagnosis, allowable prior therapy, and disease measurability requirements:

A. Dose Escalation Phase: All patients must have a pathologically documented, definitively diagnosed, advanced solid tumor that is refractory to standard treatment, for which no standard treatment is available, or the patient refuses standard therapy. Enrollment without prior documentation of tumor FOLR1 expression will be limited to the following histologic subtypes, which have a high incidence of FOLR1 positivity:

  1. Serous or endometrioid epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer
  2. Serous or endometrioid endometrial cancer
  3. Adenocarcinoma or BAC NSCLC
  4. Clear cell renal carcinoma
  5. Additional tumor types may be eligible, but require documented expression of FOLR1 (≥1 focal) by IHC (see Laboratory Manual for IHC screening procedures)
  6. There is no upper limit on the number of prior cytotoxic or targeted therapies the patient may have received. Patients may have received prior treatment with investigational compounds targeting folate receptor.
  7. Patients must have measurable or non-measurable disease.

B. Dose Expansion Cohort 1: Patients must have EOC, which is resistant to platinum-based chemotherapy:

  1. Patients must have histologically-confirmed EOC, primary peritoneal cancer or fallopian tube cancer
  2. Patients must have confirmation of ≥3 heterogeneous FOLR1 positivity by IHC.
  3. Patients must have received prior platinum-based therapy for management of disease.
  4. Patients with platinum refractory disease (those who have not responded to a platinum-based regimen or experienced disease recurrence within 3 months of completing their last platinum-based regimen) are excluded.
  5. Patients with clear cell or low grade serous ovarian cancer are excluded
  6. Patients must not have received more than 3 prior systemic cytotoxic chemotherapy regimens; however, prior treatment with folate receptor-targeting agents is not allowed.

    NOTE: There are certain instances in which patients may have received more than 3 prior regimens, but may be considered for inclusion after discussion and agreement between investigator and Sponsor.

  7. Patients may have received additional therapy with targeted agents (no upper limit), except those directed at FOLR1.
  8. Patients must have at least one lesion that meets the definition of measurable according to RECIST 1.1 (Appendix D).

C. Dose Expansion Cohort 2: Patients must have relapsed or refractory EOC, which is amenable to biopsy

  1. Patients must have histologically-confirmed EOC, primary peritoneal cancer or fallopian tube cancer who have progressed during or following completion of standard therapy.
  2. Patients must be willing to undergo tumor biopsy prior to the first dose of IMGN853 and 7±3 days after the first IMGN853 dose.
  3. Patients must have confirmation of ≥3 heterogeneous FOLR1 positivity by IHC.
  4. There is no upper limit on the number of prior treatment regimens (cytotoxic and/or targeted therapies) the patient may have received; however, prior treatment with folate-receptor targeting agents is not allowed.
  5. Patients must have measurable or non-measurable disease that can be safely biopsied.

D. Dose Expansion Cohort 3: Patients must have a histologically or cytologically-confirmed diagnosis of NSCLC adenocarcinoma or BAC, and must be refractory to or intolerant of standard therapy

  1. Patients must have confirmation of ≥ 2 heterogeneousFOLR1-positivity by IHC.
  2. There is no upper limit on the number or prior treatment regimens the patient may have received (cytotoxic and/or targeted therapies); however, prior treatment with folate-receptor-targeting agents is not allowed.
  3. Patients may have measurable or non-measurable disease.

E. Dose Expansion Cohort 4: Patients must have histologically-confirmed diagnosis of endometrial cancer (serous, endometrioid or mixed serous endometrioid). Patients with clear cell, sarcomatous or squamous histology are excluded).

  1. Patients must have received at least one platinum-based chemotherapy regimen and no more than 3 prior systemic treatment regimens (including cytotoxic chemotherapy, hormonal therapy, and targeted therapy, or any other investigational treatment in the adjuvant or the metastatic setting) for EC.

    NOTE: There are certain instances in which patients may have received more than 3 prior regimens, but may be considered for inclusion after discussion and agreement between investigator and Sponsor.

  2. Patients must have confirmation of > 2 heterogeneous FOLR1 positivity by IHC.
  3. Patients may have measurable or non-measurable disease.

3.1.1. Inclusion Criteria (All Patients)

  1. Patients must be willing to provide an archival tumor tissue block or slides for biomarker analysis
  2. > 18 years old at the time of informed consent
  3. ECOG Performance Status 0 or 1
  4. Time from Prior Therapy:

    1. Systemic Anti-Neoplastic Therapy: five half-lives or four weeks, whichever is shorter (6 weeks for prior nitrosoureas or mitomycin C)
    2. Radiotherapy: wide-field radiotherapy (e.g. > 30% of marrow-bearing bones) completed at least four weeks, or focal radiation completed at least two weeks, prior to starting study drug
  5. Patients must have recovered or stabilized from all therapy-related toxicities.
  6. Major surgery (not including placement of vascular access device or tumor biopsies) must be completed four weeks prior to Day 1. Patients must have recovered or stabilized from the side effects prior to study treatment.
  7. Patients must have adequate hematologic, liver and kidney function as defined by the following parameters:

    1. Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
    2. Platelet count ≥ 100.0 x 109/L (must not have been transfused within previous 10 days)
    3. Hemoglobin ≥ 9.0 g/dL,
    4. Serum creatinine ≤ 1.5 x upper limit of normal (ULN) or 24-hour creatinine clearance of ≥ 60 mL/minute,
    5. AST ≤ 2.5 x ULN; ALT ≤ 2.5 x ULN (AST, ALT < 5 x ULN if liver metastases), and
    6. Serum bilirubin ≤ 1.5 x UNL
  8. Patients with CNS disease involvement are eligible if they have had brain metastases resected or have received radiation therapy ending at least 4 weeks prior to study day 1 and they meet all of the following criteria: (1) residual neurological symptoms ≤ grade 1 (2) No dexamethasone requirement, and (3) Follow-up MRI shows no progression of treated lesions and no new lesions appearing.
  9. Patients must be willing and able to sign the informed consent form, and to adhere to the study visit schedule and other protocol requirements.
  10. Women of child bearing potential (WCBP), defined as a sexually mature woman who has not undergone surgical sterilization or who has not been naturally postmenopausal for at least 12 consecutive months (i.e., who has had menses any time in the preceding 12 consecutive months) must agree to use effective contraceptive methods; examples include oral, parenteral, or implantable hormonal contraceptive, intra-uterine device, barrier contraceptive with spermicide, partner's latex condom or vasectomy) while on study treatment and for at least twelve weeks after the last dose of study drug.
  11. WCBP must have a negative pregnancy test prior to the first dose of study treatment
  12. Male patients must agree to use a latex condom even if he has had a successful vasectomy and continue to follow these requirements for at least twelve weeks following the last dose of study drug.

3.1.2. Exclusion Criteria (All Patients)

  1. Grade >1 neuropathy
  2. Any active or chronic corneal disorder.
  3. Serious concurrent illness, including, but not limited to the following:

    1. Clinically relevant active infection including known active hepatitis B or C, Human Immunodeficiency Virus (HIV) infection, varicella-zoster virus (shingles) or cytomegalovirus infection or any other known concurrent infectious disease, requiring IV antibiotics within 2 weeks of study enrollment.
    2. Significant cardiac disease such as recent myocardial infarction (≤ 6 months prior to Day 1), unstable angina pectoris, uncontrolled congestive heart failure (New York Heart Association > class II), uncontrolled hypertension (≥ CTCAE v4.03 Grade 3), uncontrolled cardiac arrhythmias, severe aortic stenosis, or ≥ grade 3 cardiac toxicity following prior chemotherapy.
    3. History of multiple sclerosis or other demyelinating disease, Eaton-Lambert syndrome (para-neoplastic syndrome), history of hemorrhagic or ischemic stroke within the last 6 months, or alcoholic liver disease.
  4. Any other concomitant anti-cancer treatment such as immunotherapy, biotherapy, radiotherapy, chemotherapy, investigative therapy, or high-dose steroids; however, low-dose steroids and Luteinizing Hormone Releasing Hormone (LHRH) at doses that have been stable for ≥ 14 days are permitted for patients with prostate cancer.
  5. Known hypersensitivity to previous monoclonal antibody therapy or maytansinoids.
  6. Prior history of solid tumor malignancy within the last 3 years except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, in situ breast cancer, in situ prostate cancer (patients must have shown no evidence of active disease for 2 years prior to enrollment).
  7. Concomitant administration of folate-containing vitamins.
  8. Currently receiving anticoagulation with therapeutic doses of warfarin (low-dose warfarin < 2 mg/day is permitted). Thrombosis prophylaxis with low molecular weight heparins, aspirin (81 mg QD), or low dose oral Coumadin (≤ 2 mg QD) is allowed.
  9. Patients who have received prior allogeneic or autologous bone marrow transplants
  10. WCBP who are pregnant or breast feeding.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01609556

Locations
United States, Kansas
University of Kansas Medical Center Research Institute Recruiting
Fairway, Kansas, United States, 66205
Contact: Jan Ward    913-588-4769    jward3@kumc.edu   
Principal Investigator: Raymond Perez, MD         
United States, Massachusetts
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02062
Contact: Meghan Comeau    617-726-0491    mdcomeau@partners.org   
Principal Investigator: Michael J Birrer, M.D., Ph.D.         
United States, Michigan
Barbara Ann Karmanos Cancer Institute Recruiting
Detroit, Michigan, United States, 48201
Contact: Andrea Wolfe    315-576-9365    wolfea@karmanos.org   
Principal Investigator: Patricia M LoRusso, DO         
United States, Ohio
Ohio State University Recruiting
Columbus, Ohio, United States, 43210
Contact: Pamela Rollins    614-366-9085    pamela.rollins@osumc.edu   
Principal Investigator: David O'Malley, MD         
United States, Oklahoma
University of Oklahoma Stephenson Cancer Center Recruiting
Oklahoma City, Oklahoma, United States, 73104
Contact: Kimberly Benjamin    405-271-8778 ext 48876    Kimberly-Benjamin@ouhsc.edu   
Principal Investigator: Kathleen Moore, M.D.         
United States, Pennsylvania
Fox Chase Cancer Center Recruiting
Philadelphia, Pennsylvania, United States, 19111
Contact: Kelly M Field, BS    215-214-1685    Kelly.Field@fccc.edu   
Principal Investigator: Hossein Borghaei, MS, DO         
United States, Tennessee
Sarah Cannon Research Institute Recruiting
Nashville, Tennessee, United States, 37203
Contact: Kimberly McKenzie    615-524-4255    Kimberly.McKenzie@scresearch.net   
Contact: Lorie Patterson    615-329-7289    lorie.patterson@scresearch.net   
Principal Investigator: Todd M Bauer, MD         
United States, Texas
CTRC at the University of Texas Health Science Center Recruiting
San Antonio, Texas, United States, 78229
Contact: Leslie Wood, RN, BSN, OCN    210-450-5962    woodl3@uthscsa.edu   
Principal Investigator: Kamalesh K Sankhala, M.D.         
Sponsors and Collaborators
ImmunoGen, Inc.
  More Information

No publications provided

Responsible Party: ImmunoGen, Inc.
ClinicalTrials.gov Identifier: NCT01609556     History of Changes
Other Study ID Numbers: IMGN853-0401
Study First Received: May 30, 2012
Last Updated: June 26, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by ImmunoGen, Inc.:
FOLR solid tumors

Additional relevant MeSH terms:
Ovarian Neoplasms
Neoplasms
Endocrine Gland Neoplasms
Neoplasms by Site
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders

ClinicalTrials.gov processed this record on August 28, 2014