This Phase 1b trial is an open-label, multi-center study of XMT-1592 administered as an
intravenous infusion once every 3 weeks. The dose-escalation (DES) segment of the study will
establish the expansion (EXP) dose and is intended to establish the maximum tolerated dose
(MTD) or recommended Phase 2 dose (RP2D) for XMT-1592 in patients with high grade serous
ovarian cancer (HGSOC) or non-small cell lung cancer (NSCLC), adenocarcinoma subtype. The EXP
segment of the study will consist of 2 parallel cohorts of patients (HGSOC and NSCLC) to
confirm the MTD or RP2D and estimate the objective response rate in each selected patient
population. In DES, the observation period for dose-limiting toxicities is 21 days, between
Day 1 through the end of Cycle 1 which includes the pre-dose assessments before receiving the
Cycle 2 dose. All adverse events (AEs) will be graded according to NCI, CTCAE v5.0). In
general, AEs ≥Grade 3 are dose-limiting toxicities with some modifications.
- Ability to give informed consent.
- ECOG performance status 0 or 1.
- Measurable disease as per RECIST, version 1.1. Resolution of all acute toxic effects
of prior therapy or surgical procedures to Grade ≤1 (except alopecia).
- Adequate organ function.
- Confirmed availability of tumor tissue blocks or freshly cut tissue slides for NaPi2b
testing. -In EXP, ability to undergo a fresh biopsy before enrollment, unless not
- For women of childbearing potential and men with partners of childbearing potential,
agreement to use a highly effective form of hormonal contraception or two effective
forms of non-hormonal contraception by the patient and/or partner, and to continue the
use of contraception for the duration of study treatment and for at least 6 months
after the last dose of study treatment.
- Histologically or cytologically confirmed solid tumors of the types specified below,
with incurable, locally advanced or metastatic disease that has failed standard
therapy or for which no standard treatment option exists.
- Ovarian Cancer: Histological diagnosis of epithelial ovarian, fallopian tube, or
primary peritoneal cancer, excluding the mucinous subtype.
NSCLC: Histological diagnosis of nonsquamous NSCLC.
- Major surgery within 28 days of starting study treatment; -or- systemic anti-cancer
therapy within the lesser of 28 days or 5 half-lives of the prior therapy before
starting study treatment -or- recent radiation therapy with unresolved toxicity.
- Brain metastases that are: untreated, progressive, have required any type of major
treatment, e.g., whole-brain radiation treatment, adjuvant chemotherapy, gamma knife,
to control symptoms from brain metastases within 30 days of the first study treatment.
Or any history of leptomeningeal metastasis.
- Current known active infection with HIV, hepatitis B virus, or hepatitis C virus.
- No prior history of liver disease such as liver cirrhosis, hepatic fibrosis
- Current severe, uncontrolled systemic disease (e.g., clinically significant
cardiovascular, pulmonary, or metabolic disease) or intercurrent illness that could
interfere with per-protocol evaluations.
- Severe dyspnea at rest due to complications of advanced malignancy, or requiring
supplementary oxygen therapy.
- Currently active pneumonitis or interstitial lung disease.
- Pregnant or nursing women.
- History of other malignancy within the last 5 years, except for appropriately treated
carcinoma in situ of the cervix, non-melanoma skin carcinoma, or other malignancy with
a similar expected curative outcome.
- Participation in the DES component of the study.
- Prior use of mirvetuximab soravtansine or another ADC containing an auristatin or