First-in-human, Phase 1b safety study of the antibody-drug conjugate (ADC) XMT-1536
administered as an intravenous infusion once every four weeks. Patients with tumor types
likely to express NaPi2b were enrolled in dose escalation. Patients with platinum-resistant
ovarian cancer and non-small cell lung cancer (adenocarcinoma subtype) are being enrolled in
the expansion segment of this study. In addition to safety assessments, the pharmacokinetics
of the drug will be assessed along with ADC activity.
This is a multi-center study of XMT-1536 in patients with tumors likely to express NaPi2b,
focusing on patients with platinum-resistant ovarian cancer and non-small cell lung cancer,
adenocarcinoma subtype. XMT-1536 will be administered as an intravenous infusion once every
four weeks. The study consists of two segments: dose escalation (DES) and expansion (EXP).
The DES segment studies small groups of patients who receive increased doses. A Safety Review
Committee has been established to review the data from each dose level before moving to the
next higher dose. Dose escalation will stop when a patient or patients experience 2 or more
dose-limiting events. Enrollment into the EXP segment consists of 2 parallel cohorts of
patients to confirm the dose that has been identified in DES and estimate the objective
response rate in each patient population. All adverse events will be graded according to the
National Cancer Institute (NCI) Common Terminology Criteria version (CTCAE v4.03). Throughout
the study, pharmacokinetics will be measured using proprietary assays developed by Mersana.
Anti-cancer activity will be measured via RECIST.
- 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.
For Ovarian Cancer
- Histological diagnosis of epithelial ovarian, fallopian tube, or primary peritoneal
cancer, excluding the mucinous subtype.
- Platinum resistance, defined as disease progression within 6 months of completing a
platinum-containing chemotherapy regimen.
- Not more than 3 prior lines of systemic chemotherapy for ovarian cancer.
- Prior use of maintenance therapy is not a line of treatment and is allowed. For NSCLC
- Histological diagnosis of nonsquamous NSCLC.
- Prior treatment with a platinum-based (cisplatin or carboplatin) regimen and a PD-1 or
PD-L1 monoclonal antibody (either in combination or sequentially).
- Patients with known oncogenic mutations for which there are approved therapies must
have documented intolerance or disease progression for the approved therapies for
- 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:
1. Are untreated.
2. Are progressive.
3. Or 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.
4. 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