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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


Phase 1
18 Years
N/A
Open (Enrolling)
Both
FOLR-1 Postive Solid Tumors

Thank you

Trial Information

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


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. 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 endometrial cancer

3. Adenocarcinoma or BAL NSCLC

4. Clear cell renal carcinoma

5. Additional tumor types may be eligible, but require documented expression of
FOLR1 (≥1 focal) by IHC (see IMGN853 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 FOLR1.

7. Patients must have measurable or non-measurable disease.

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

1. Patients must have histologically-confirmed EOC, primary peritoneal cancer or
fallopian tube cancer

2. Patients must have confirmation of ≥2 heterogeneous FOLR1 positivity by IHC.

3. Patients must have received prior platinum-based therapy for management of
primary disease but must not have received more than 2 prior systemic cytotoxic
chemotherapy regimens. If the patient has received a second cytotoxic regimen,
this regimen should not have included a platinum component.

4. Patients may have received additional therapy with targeted agents (no upper
limit), except those directed at FOLR1.

5. 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 ≥2 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 FOLR1-targeted 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, and must be refractory to
or intolerant of standard therapy

1. Patients must be willing to undergo 18FLT-PET imaging and/or tumor biopsy prior
to the first dose of IMGN853 and 7±3 days after the first IMGN853 dose.

2. Patients must have confirmation of ≥ 2 heterogeneousFOLR1-positivity by IHC

3. 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 FOLR1-targeted agents is not allowed.

4. Patients must have measurable or non-measurable disease.

2. Patients with accessible malignant effusions, such as ascites, must sign an
additional informed consent to have serial biopsy to measure soluble FOLR1 (pre-dose
and 7±3 days after the first IMGN853 dose).

3. Patients must be willing to provide an archival tumor tissue block or slides for
biomarker analysis

4. > 18 years old at the time of informed consent;

5. ECOG Performance Status 0 or 1

6. 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

7. Patients must have recovered or stabilized from all therapy-related toxicities.

8. 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.

9. 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 ≥ 1.0 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

10. 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.

11. Patients must be willing and able to sign the informed consent form, and to adhere to
the study visit schedule and other protocol requirements

12. 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.

13. WCBP must have a negative pregnancy test prior to the first dose of study treatment

14. 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.

Exclusion Criteria:

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).

9. Patients who have received prior allogeneic or autologous bone marrow transplants

10. WCBP who are pregnant or breast feeding

Type of Study:

Interventional

Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Determine Maximum Tolerated Dose and Recommended Phase II Dose of IMGN853 when administered intravenously every 3 weeks

Outcome Time Frame:

During study

Safety Issue:

Yes

Authority:

United States: Food and Drug Administration

Study ID:

IMGN853-0401

NCT ID:

NCT01609556

Start Date:

May 2012

Completion Date:

March 2015

Related Keywords:

  • FOLR-1 Postive Solid Tumors
  • FOLR solid tumors
  • Ovarian Neoplasms
  • Neoplasms

Name

Location

Barbara Ann Karmanos Cancer InstituteDetroit, Michigan  48201
Massachusetts General HospitalBoston, Massachusetts  02114-2617
CTRC at The University of Texas Health Science CenterSan Antonio, Texas  78229
University of Oklahoma Stephenson Cancer CenterOklahoma City, Oklahoma  73104