A Study of SGN-B7H4V in Advanced Solid Tumors

Overview

About this study

The purpose of this study is to test the safety and side effects of a drug called SGN-B7H4V in participants with solid tumors.  A side effect is anything a drug does to the body besides treating the disease. Participants will have cancer that has spread in the body near where it started (locally advanced) and cannot be removed (unresectable) or has spread through the body (metastatic). This study will have three parts. Parts A and B of the study will find out how much SGN-B7H4V should be given to participants. Part C will use the dose found in Parts A and B to find out how safe SGN-B7H4V is and if it works to treat solid tumor cancers.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria:

- Participants must have one of the following histologically or cytologically confirmed
locally advanced unresectable or metastatic solid tumor types:

- High-grade serous epithelial ovarian cancer, primary peritoneal cancer, or
fallopian tube cancer

- HER2-negative, HR positive breast cancer

- Triple-negative breast cancer (TNBC)

- Endometrial carcinoma

- Non-small cell lung cancer (Squamous cell carcinoma [SqCC], Adenocarcinoma [AC])

- Cholangiocarcinoma or gallbladder carcinoma

- Adenoid cystic carcinoma (ACC) of the head and neck

- Parts A and B: Participants must have disease that is relapsed or refractory or be
intolerant to SOC therapies, and, in the judgement of the investigator, should have no
appropriate SOC therapeutic option

- Part C: Participants must have disease that is relapsed or refractory or be intolerant
to SOC therapies, unless contraindicated

- High-grade serous ovarian cancer (epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer):

- Subjects must have platinum-resistant or -refractory disease, defined as having progressed, with evidence of radiographic progression, or relapsed during or within 6 months after previous platinum-containing chemotherapy. If eligible, subject must have received a bevacizumab-containing regimen. If eligible by biomarker status and consistent with SOC, must have received a poly-ADP ribose polymerase (PARP) inhibitor;

- Advanced HER2-negative, HR-positive breast cancer or TNBC (per American Society for Clinical Oncology [ASCO]/College of American Pathologists 2018 guidelines):

- Subjects must have received 1 or more prior lines of therapy for locally advanced or metastatic disease. Prior therapies must include a taxane administered either as single agent or in combination;

- Subjects with HR-positive disease additionally must have received cyclin D-cyclin dependent kinase (CDK)4/6-inhibitor therapy unless contraindicated, and at least 1 prior hormonal therapy;

- If eligible by biomarker status and consistent with SOC, must have received a PARP inhibitor, PD-(L)1 inhibitor, and/or phosphoinositide 3-kinase (PI3K) inhibitor;

- For subjects with TNBC and HER2-negative, HR-positive breast cancer, when applicable, the investigator has discussed sacituzumab govitecan as a treatment option, if available;

- Subjects with TNBC must not have received prior hormone therapy.

- Endometrial carcinoma:

- subjects must have received at least 1 line of systemic therapy

- If appropriate by biomarker status (including but not limited to microsatellite instability [MSI] and mismatch repair deficient [dMMR] status) and available per local SOC, must have received a prior PD-1 inhibitor and/or the combination of pembrolizumab and lenvatinib.

- Subjects must have received at least 1 prior platinum-based regimen for metastatic endometrial cancer.

- Squamous NSCLC:

- Subjects with locally advanced recurrent/metastatic disease must have received prior treatment with platinum-based therapy and a PD-(L)1 inhibitor (if indicated per local SOC), separately or in combination.

- Cholangiocarcinoma or gallbladder carcinoma:

- Subjects must have received at least 1 line of systemic therapy;

- If appropriate by biomarker status (including but not limited to neurotrophic tyrosine kinase receptor [NTRK], fibroblast growth factor receptor [FGFR]2 genetic alterations, MSI-high, and/or high tumor mutational burden [TMB-H] status) and available per local SOC, subjects must have received approved targeted therapy;

- Hepatic involvement is allowed

- Adenoid Cystic Carcinoma:

- Subjects with locally advanced recurrent/metastatic disease must have received at least 1 line of systemic therapy. o Subjects whose tumors harbor genomic mutations/alterations for which approved targeted therapies are available per local SOC, must have received approved and available targeted therapies.

- Tumor tissue is required for enrollment.

- For Part A and Part B, archival tumor tissue from most recent biopsy collected within 24 months of enrollment is required, if available.* For all subjects in Part C (disease-specific cohorts and biology cohort), archival tumor tissue from most recent biopsy collected within 12 months of enrollment is required, if available. If archival tissue is not available for subjects in Part A, Part B, and Part C disease-specific cohorts, a fresh pre-treatment biopsy must be submitted (appropriate lesions are accessible with a minimally invasive procedure that does not represent significant risk). *For Part A subjects enrolled for additional dose exploration, archival tumor tissue from most recent biopsy collected within 12 months of enrollment is required, if available. For all other Part A subjects, archival tumor tissue from most recent biopsy collected within 24 months of enrollment is required, if available.

- For the Part C biology cohort, a fresh pre-treatment biopsy, an on-treatment biopsy on Cycle 1 Day 15, and an end of treatment (EOT) biopsy are required.

- Age 18 years or older

- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1

- Measurable disease per RECIST version 1.1 at baseline

- The following baseline laboratory test results:

- Absolute neutrophil count (ANC) ≥1500/µL;

- Hemoglobin (Hgb) ≥ 9 g/dL;

- Platelet count ≥ 100,000/μL;

- Serum bilirubin ≤ 1.5 × upper limit of normal (ULN) or ≤ 3 × ULN for subjects with Gilbert’s disease;

- Estimated glomerular filtration rate (eGFR) ≥ 45 mL/min/1.73 m^2 using the Modification of Diet in Renal Disease (MDRD) study equation as applicable;

- ALT and AST ≤ 3 × ULN (≤ 5 × ULN if there is evidence of hepatic involvement by malignant disease)

- Subjects of childbearing potential are eligible under the following conditions:

- Must have a negative serum or urine pregnancy test (minimum sensitivity 25 mIU/mL or equivalent units of beta human chorionic gonadotropin [β-hCG]) result within 7 days prior to the first dose of SGN-B7H4V. Subjects with false positive results and documented verification that the subject is not pregnant are eligible for participation;

- Must agree not to try to become pregnant during the study and for at least 2 months after the final dose of SGN-B7H4V;

- Must agree not to breastfeed or donate ova, starting at time of informed consent and continuing through 2 months after the final dose of SGN-B7H4V;

- If sexually active in a way that could lead to pregnancy, must consistently use at least 2 acceptable methods of birth control (contraception), at least 1 of which must be highly effective from the time of informed consent and continuing through at least 2 months after the final dose of SGN-B7H4V 

- Subjects who can get someone pregnant under the following conditions:

- Must agree not to donate sperm from the time of informed consent and continuing through the study period and at least 4 months after the final dose of SGN-B7H4V;

- If sexually active with a person of childbearing potential in a way that could lead to pregnancy, must consistently use at least 2 acceptable methods of birth control (contraception), at least 1 of which must be highly effective from the time of informed consent and continuing through at least 4 months after the final dose of SGN-B7H4V;

- If sexually active with a person who is pregnant or breastfeeding, must consistently use a condom from the time of informed consent and continuing through at least 4 months after the final dose of SGN-B7H4V.

Exclusion Criteria:

- History of another malignancy within 3 years before the first dose of study drug. Any
evidence of residual disease from a previously diagnosed malignancy. Exceptions are
malignancies with a negligible risk of metastasis or death.

- Known active central nervous system metastases. Participants with previously treated
brain metastases may participate provided they:

- are clinically stable for at least 4 weeks prior to study entry after brain
metastasis treatment

- have no new or enlarging brain metastases

- and are off corticosteroids prescribed for symptoms associated with brain
metastases for at least 7 days prior to the first dose of study treatment.

- Carcinomatous meningitis

- Previous receipt of an MMAE-containing agent or an agent targeting B7-H4

- Pre-existing neuropathy ≥ Grade 2 per National Cancer Institute (NCI) Common
Terminology Criteria for Adverse Events (CTCAE) Version 5.0

- Corneal disease or injury requiring treatment or active monitoring

Note: Other protocol defined Inclusion/Exclusion Criteria may apply.

Eligibility last updated 1/12/24. Questions regarding updates should be directed to the study team contact.

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Jacksonville, Fla.

Mayo Clinic principal investigator

Gerardo Colon-Otero, M.D.

Closed for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

More information

Publications

Publications are currently not available
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CLS-20534788

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