CLINICAL TRIAL / NCT05527184
First in Human Study of IMGN151 in Recurrent Gynaecological Cancers
- Interventional
- Active
- NCT05527184
Contact Information
A Phase 1, First-in-Human, Open-Label, Dose-Escalation and Expansion Study of IMGN151 (Anti-FRα Antibody-drug Conjugate) in Adult Patients With Recurrent Gynaecological Cancers
IIMGN151-1001 is a Phase 1, first in human, open-label dose-escalation, optimization, and expansion study designed to characterize the safety, tolerability, pharmacokinetics (PK), immunogenicity, and preliminary antitumor activity of IMGN151 in adult participants with recurrent endometrial cancer; recurrent, high-grade serous epithelial ovarian, fallopian tube, and primary peritoneal cancers; or recurrent cervical cancers. All participants will be, in the opinion of the investigator, appropriate for nonplatinum single-agent therapy for their next line of therapy.
Participants may continue on study drug based on clinical benefit until disease
progression, adverse event (AE) requiring discontinuation, withdrawal of consent,
physician decision, or other discontinuation criteria are met.
Gender
Female
Age Group
18 Years and up
Accepting Healthy Volunteers
No
Inclusion Criteria:
1. Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1.
2. Dose-Escalation Phase: Recurrent endometrial cancer or high-grade serous epithelial
ovarian, fallopian tube, and primary peritoneal cancer (EOC) and who have exhausted
appropriate standard-of-care therapy.
3. Dose Optimization: Platinum-resistant, high-grade serous EOC (PROC) with no previous
folate receptor alpha (FRα)-directed therapy. Participants with PROC will have had
no more than 5 prior lines of therapy, with no more than 2 prior therapies since
development of platinum resistance.
4. Expansion Phase:
1. For Cohort A, recurrent endometrial cancer (high-grade endometrioid or serous
histology only) with 1-3 prior lines of therapy.
2. For Cohort B, PROC with no previous FRα-directed therapy and no more than 5
prior lines of therapy, with no more than 2 prior therapies since development
of platinum resistance.
3. For Cohort C, PROC with previous FRα-directed therapy with at least one
intervening anticancer therapy between prior FRα-directed therapy and IMGN151.
4. For Cohort D, EOC of one of the following histologies: carcinosarcoma,
endometrioid, and low-grade serous carcinoma and have exhausted appropriate
standard-of-care therapy.
5. For Cohort E, cervical cancer including the following histologies: squamous
cell carcinoma, adenocarcinoma, adenosquamous carcinoma with 1-4 prior lines of
therapy.
6. For participants with cervical cancer with Combined Positive Score (CPS) > 1 or
with endometrial cancer, prior checkpoint inhibitor therapy, alone or in
combination, is required if available locally and medically appropriate.
5. Evaluable lesions
1. Dose-Escalation Phase: Participants may have radiologically evaluable or
nonevaluable disease.
2. Dose Optimization and Expansion Phase: Participants must have at least 1 lesion
that meets the definition of measurable disease by RECIST v1.1 (radiologically
measured by the investigator).
6. Willing to provide an archival tumor tissue block or slides or to undergo a
procedure to obtain a new biopsy using a low-risk, medically routine procedure.
7. Participants must have stabilized or recovered (Grade 1 or baseline) from all prior
therapy-related toxicities (except alopecia or hemoglobin within 10 days before
Cycle 1 Day 1).
8. Participants must have completed any major surgery at least 4 weeks prior to first
dose of IMGN151 and have recovered or stabilized from the side effects of prior
surgery prior to first dose of IMGN151.
9. Participants must have adequate organ and bone marrow function.
Exclusion Criteria:
1. Participants with ovarian cancer with histologies including clear cell, mucinous, or
borderline ovarian tumor.
1. With the exception of participants enrolled in Cohort D, participants with
ovarian cancer with histologies including endometrioid, sarcomatous histology,
mixed tumors containing any of the above histologies, as well as low-grade
serous carcinoma.
2. For Cohort A, participants with endometrial cancer with histologies other than
high-grade serous or high-grade endometrioid.
3. For Cohort E, participants with cervical cancer with histologies other than
adenocarcinoma, squamous cell carcinoma, and adenosquamous carcinoma.
2. For Cohort B and Dose Optimization: participants with primary platinum refractory
ovarian cancer, defined as disease progression on or within 3 months completion of
first platinum-based treatment.
3. Radiation therapy of > 20% of the potential bone marrow
4. Participants with > Grade 1 peripheral neuropathy per Common Terminology Criteria
for Adverse Events (CTCAE) v5.0
5. Participants with the following ocular history and/or concurrent disorders:
1. Active or chronic corneal epithelial disorders other than non-confluent
superficial keratopathy/keratitis, including confluent superficial punctate
keratopathy/keratitis (SPK) not expected to resolve to non-confluence or better
within the screening window with standard-of-care intervention
2. History of corneal transplantation
3. Undergoing active postoperative management for refractive surgery, cataract
surgery, corneal cross-linking, or corneal complications of surgery
4. Active or chronic clinically significant (≥ Grade 3) corneal disorders (for
example, Fuch's dystrophy or neurotrophic keratitis)
5. Active ocular conditions requiring ongoing treatment/monitoring, such as
glaucoma, which is not adequately controlled with medication or surgery, wet
age-related macular degeneration requiring intravitreal injections, active
diabetic retinopathy with macular edema, presence of papilledema, an ocular
condition with high risk of retinal detachment
6. Monocular vision with visual acuity in the worse-seeing eye (worse than 20/200
or visual fields less than 20 degrees)
6. Serious concurrent illness or clinically relevant active infection.
7. A history of multiple sclerosis or other demyelinating disease and/or Lambert-Eaton
syndrome (paraneoplastic syndrome)
8. Participants with clinically significant cardiac disease.
9. A history of hemorrhagic or ischemic stroke within 6 months before enrollment
10. A history of cirrhotic liver disease (Child-Pugh Class B or C)
11. Participants with evidence of pneumonitis on baseline imaging or Participants with a
previous clinical diagnosis of noninfectious interstitial lung disease (ILD),
including noninfectious pneumonitis
12. Participants with prior hypersensitivity to monoclonal antibodies (mAb)
13. Females who are pregnant or breastfeeding
14. For Dose Optimization and Expansion Phase: Participants who received a prior
FRα-targeting agent, with the exception of participants enrolled in the prior
FRα-targeting agent, ovarian cancer cohort (Cohort C).
15. Untreated or symptomatic central nervous system metastases
16. A history of other malignancy within 3 years before enrollment