First trial in humans testing the safety and efficacy of IMGN151 in women with recurrent gynaecological cancers

Overview

Sponsor-declared trial summary

Key facts

Sponsor

AbbVie Deutschland GmbH & Co. KG

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

19 May 2025 → ongoing

Decision date (initial)

2024-08-13

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

AbbVie Deutschland GmbH & Co. KG

External identifiers

EU CT number

2023-506842-22-00

ClinicalTrials.gov

NCT05527184

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Dose response, Safety, Pharmacokinetic

Co-Primary Objectives
• To assess safety and tolerability, including dose-limiting toxicities (DLTs), maximum tolerated dose (MTD), or maximum administered dose (MAD; if no MTD is defined) of IMGN151 when administered intravenously
• To determine the recommended dose of IMGN151 monotherapy

Secondary objectives 3

1. To characterize the pharmacokinetics (PK) and immunogenicity of IMGN151
2. To assess objective response rate (ORR) for IMGN151
3. To assess duration of response (DOR) for IMGN151

Conditions and MedDRA coding

Recurrent endometrial cancer, recurrent epithelial ovarian, fallopian tube, and primary peritoneal cancer (EOC), recurrent cervical cancer

Study design 3 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 16

1. Subjects ≥ 18 years of age.
2. An Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1.
3. Dose-Escalation Phase: A confirmed diagnosis of recurrent endometrial cancer (endometrioid or serous histology only) or high-grade serous epithelial ovarian, fallopian tube, and primary peritoneal cancer (EOC). Subjects will have exhausted appropriate standard-of-care therapy and be appropriate for participation in a single-agent Phase 1 study in the opinion of the investigator.
4. If performed previously, results of germline and/or somatic BRCA testing must be reported at study entry. Subjects with PROC with tumors harboring a BRCA mutation are required to have received prior treatment with a poly (ADP-ribose) polymerase (PARP) inhibitor if available locally and medically appropriate. Note that BRCA testing is not required for enrollment for subjects who have not had it done previously.
5. Dose Optimization: a. A confirmed diagnosis of platinum-resistant, high-grade serous EOC (PROC) with no previous FRα-directed therapy. Subjects 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. Platinum-resistant disease is defined as radiographic progression within 6 months (up to 182 days) after the last dose of the most recent platinum therapy. Note: Progression is calculated from the date of the last administered dose of platinum therapy to the date of the radiographic imaging showing progression.
6. Expansion Phase: a. For Cohort A, a confirmed diagnosis of recurrent endometrial cancer (high-grade [Grade 3] endometrioid or serous histology only). Subjects with endometrial cancer will have had 1-3 prior lines of therapy. b. For Cohort B, a confirmed diagnosis of high-grade serous PROC with no previous FRα-directed therapy. Subjects 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. Platinum-resistant disease is defined as radiographic progression within 6 months (up to 182 days) after the last dose of the most recent platinum therapy. c. For Cohort C, a confirmed diagnosis of high-grade serous PROC with previous FRα-directed therapy other than mirvetuximab soravtansine. d. For Cohort D, a confirmed diagnosis of EOC of one of the following histologies: carcinosarcoma, endometrioid, and low-grade serous carcinoma. Mixed histologies of these listed histologies only are acceptable. Borderline tumors are excluded. Subjects will have exhausted appropriate standard-of-care therapy and, in the opinion of the investigator, be appropriate for participation in a single-agent Phase 1 study. e. For Cohort E, a confirmed diagnosis of cervical cancer including the following histologies: squamous cell carcinoma, adenocarcinoma, adenosquamous carcinoma. Subjects with cervical cancer will have had 1-4 prior lines of therapy. Subjects will have exhausted appropriate standard-of-care therapy and, in the opinion of the investigator, be appropriate for participation in a single-agent Phase 1 study. f. For subjects 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.
7. Prior anticancer therapy a. Neoadjuvant and adjuvant therapies are considered 1 line of therapy. b. Maintenance therapy (eg, bevacizumab or PARP inhibitors) will be considered part of the preceding line of therapy (ie, not counted independently). c. Therapy changed due to toxicity in the absence of progression will be considered part of the same line (ie, not counted independently). d. Hormonal therapy alone will not be counted as a separate line of therapy. Hormonal therapy in combination with non-hormonal agents (eg, everolimus and letrozole) will be counted as a line of therapy. e. For Cohort C: Prior FRα-targeting therapy other than mirvetuximab soravtansine is required. f. For Cohorts A and E: Radio-sensitizing chemotherapy, if only given with radiation therapy, is not considered a line of therapy.
8. Evaluable lesions a. Dose-Escalation Phase: Both radiologically evaluable and nonevaluable disease is acceptable. b. Dose Optimization and Expansion Phase: Subjects must have at least 1 lesion that meets the definition of measurable disease by RECIST v1.1 (radiologically measured by the investigator).
9. An archival tumor tissue block or slides, or a procedure to obtain a new biopsy using a low-risk, medically routine procedure for retrospective IHC confirmation of FRα status is required. a. Expansion Phase: For subjects with ovarian cancer enrolled in the prior FRα-targeting agent exposure cohort (Cohort C), in addition to providing an archival tissue from prior to receipt of prior FRα-targeting agent, subjects are required to provide a second tumor tissue sample after completion of prior FRα-targeting therapy and before the start of IMGN151 treatment.
10. Completed prior therapy within the specified times below: a. Systemic antineoplastic therapy completed at least 5 half-lives or 4 weeks (whichever is shorter) before planned first dose of IMGN151. Radiographic PD per investigator is required on most recent therapy for dose optimization and expansion. b. Focal radiation completed at least 2 weeks before planned first dose of IMGN151.
11. Stabilized or recovered (Grade 1 or baseline) from all prior therapy-related toxicities (except alopecia or hemoglobin within 10 days before C1D1).
12. Completed any major surgery at least 4 weeks before first dose of IMGN151 and have recovered or stabilized from the side effects of prior surgery before first dose of IMGN151.
13. Adequate hematologic, liver, and kidney functions defined as follows: a. Absolute neutrophil count (ANC) ≥ 1.5 × 109/L (1500/μL) without granulocyte colony-stimulating factor (G-CSF) in the prior 10 days or long-acting white blood cell growth factors in the 20 days before C1D1 b. Platelet count ≥ 100 × 109/L (100,000/μL) without platelet transfusion in the 10 days before C1D1 c. Hemoglobin ≥ 9.0 g/dL without packed red blood cell transfusion in the 10 days before C1D1 d. Estimated glomerular filtration rate (eGFR) ≥ 45 mL/min/1.73 m2 or an estimated creatinine clearance (CrCL) of ≥ 45 mL/min, calculated using CKD-EPI equation or Cockcroft-gault formula (Appendix G) e. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3.0 × upper limit of normal (ULN) f. Bilirubin ≤ 1.5 × ULN (subjects with documented diagnosis of Gilbert syndrome are eligible if total bilirubin < 3.0 × ULN) g. Albumin ≥ 2 g/dL
14. Subjects or their legally authorized representative(s) must be willing and able to sign the informed consent form (ICF) and to adhere to the protocol requirements.
15. Subjects assigned female at birth of childbearing potential (FOCBP) must agree to use highly effective contraceptive method(s) while on IMGN151 and for at least 28 weeks after the last dose.
16. For FOCBP, a negative serum pregnancy test at Screening and a negative serum or urine pregnancy test within 72 hours before first dose of IMGN151 is required.

Exclusion criteria 18

1. Subjects with ovarian cancer with histologies including clear cell, mucinous, or borderline ovarian tumor. a. With the exception of subjects enrolled in Cohort D, subjects with ovarian cancer with histologies including endometrioid, sarcomatous histology, mixed tumors containing any of the above histologies, as well as low-grade serous carcinoma. b. For Cohort A, subjects with endometrial cancer with histologies other than serous or high-grade (Grade 3) endometrioid. c. For Cohort E, subjects with cervical cancer with histologies other than adenocarcinoma, squamous cell carcinoma, and adenosquamous carcinoma.
2. For Cohort B and Dose Optimization: subjects with primary platinum refractory ovarian cancer, defined as disease progression on or within 3 months of completion of first platinum-based treatment.
3. Radiation therapy of > 20% of the potential bone marrow Note: For subjects with endometrial or cervical cancer: Whole pelvic radiation therapy (WPXRT) given in the upfront/adjuvant setting, ± brachytherapy, is permitted.
4. > Grade 1 peripheral neuropathy per Common Terminology Criteria for Adverse Events (CTCAE v5.0). Note: medication management to achieve Grade 1 (asymptomatic) is acceptable.
5. Subjects with the following ocular history and/or concurrent disorders: a. 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 SOC intervention b. History of corneal transplantation c. Undergoing active postoperative management for refractive surgery, cataract surgery, corneal cross-linking, or corneal complications of surgery d. Active or chronic clinically significant (≥ Grade 3) corneal disorders (eg, Fuch's dystrophy or neurotrophic keratitis) e. 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 or an ocular condition with high risk of retinal detachment f. 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, including, but not limited to the following: a. Active hepatitis B or C infection (whether or not on active antiviral therapy). b. HIV infection in subjects with CD4+ T-cell (CD4+) counts < 350 cells/µL. c. Active cytomegalovirus infection. d. Active COVID-19/SARS-CoV-2 infection. Although SARS-CoV-2 testing is not mandatory for study entry, testing should follow local clinical practice guidelines and standards. e. Any other concurrent infectious disease requiring IV antibiotics within 2 weeks before first dose of IMGN151. Note: Testing at Screening is not required for the above infections unless clinically indicated.
7. History of multiple sclerosis or other demyelinating disease and/or Lambert-Eaton syndrome (paraneoplastic syndrome).
8. Clinically significant cardiac disease including, but not limited to, any of the following: a. Myocardial infarction ≤ 6 months before first dose b. Unstable angina pectoris c. Uncontrolled congestive heart failure (New York Heart Association > class II) d. Uncontrolled ≥ Grade 3 hypertension (per CTCAE v5.0) e. Uncontrolled cardiac arrhythmias f. QTc interval > 470 ms
9. History of hemorrhagic or ischemic stroke (including transient ischemic attack) within 6 months before enrollment.
10. History of cirrhotic liver disease (Child-Pugh Class B or C).
11. Evidence of pneumonitis on baseline imaging or subjects with a previous clinical diagnosis of noninfectious interstitial lung disease (ILD), including noninfectious pneumonitis.
12. Prior hypersensitivity to monoclonal antibodies (mAb).
13. Subjects who are pregnant or breastfeeding.
14. For Dose Optimization and Expansion Phase: Receipt of a prior FRα-targeting agent, with the exception of subjects enrolled in the prior FRα-targeting agent, ovarian cancer cohort (Cohort C). Receipt of prior mirvetuximab soravtansine is excluded for all cohorts.
15. Untreated or symptomatic central nervous system metastases Note: Subjects requiring ongoing steroids for central nervous system metastases are not eligible for enrollment.
16. History of other malignancy within 3 years before enrollment Note: Subjects with tumors with a negligible risk for metastasis or death (eg, adequately controlled basal-cell carcinoma or squamous-cell carcinoma of the skin, or carcinoma in situ of the cervix or breast) are eligible.
17. Prior known hypersensitivity reactions to study drugs and/or any of their excipients.
18. Subject has received prior antibody-drug conjugate with a microtubule-targeting payload.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Co-Primary Endpoints: Incidence of adverse events (AEs), serious adverse events (SAEs), and DLTs; Determine the recommended dose of IMGN151 monotherapy

Secondary endpoints 3

1. PK parameters of IMGN151 conjugate, total antibody, DM51 and S-methyl DM51 and incidence of treatment-emergent anti-drug antibodies (ADAs)
2. ORR (which includes best response of complete response [CR] or partial response [PR] as assessed by the investigator) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria
3. DOR (defined as the time from initial response [CR or PR] until radiological progressive disease [PD] per RECIST v1.1, as assessed by the investigator, or death, whichever occurs first)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Auxiliary 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

AbbVie Deutschland GmbH & Co. KG

Sponsor organisation

AbbVie Deutschland GmbH & Co. KG

Address

Knollstrasse

City

Ludwigshafen Am Rhein

Postcode

67061

Country

Germany

Scientific contact point

Organisation

AbbVie Deutschland GmbH & Co. KG

Contact name

Global Clinical Trials Helpdesk

Public contact point

Organisation

AbbVie Deutschland GmbH & Co. KG

Contact name

Global Clinical Trials Helpdesk

Third parties 7

Locations

7 EU/EEA countries · 27 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 71 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

15 submissions — initial application plus substantial / non-substantial modifications