First-in-Human Study of XMT-1536 in Cancers Likely to Express NaPi2b

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-squamous non-small cell
lung cancer. XMT-1536 will be administered as an intravenous infusion once every three weeks.
The study consists of two segments: dose escalation (DES) and expansion (EXP). The DES
segment will study small groups of patients who receive increased doses. A Safety Review
Committee will be 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. At this point, the maximum tolerated dose or recommended Phase 2 dose
will be established and the EXP segment will begin. This segment consists of 3 parallel
cohorts of patients to confirm the MTD or RP2D and estimate the objective response rate in
each selected 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. ADC
activity will be measured via RECIST.

Inclusion Criteria:

- 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.

- 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.

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
their mutation.

For Other Indications

- For papillary thyroid carcinoma patients:

1. Progressive, radioactive iodine-refractory, loco-regional recurrent or metastatic
disease.

2. Resistance or intolerance to prior kinase inhibitor therapy (e.g., lenvatinib,
sorafenib). A patient who is considered inappropriate for, or who has refused,
kinase inhibitor therapy may be enrolled with approval of the Medical Monitor.

- For endometrial carcinoma patients, a diagnosis of epithelial endometrial carcinoma is
required. Stromal tumors and carcinosarcoma (mixed malignant Mullerian tumor) are
excluded.

- For papillary renal cell carcinoma patients, the following are required:

1. Documented local confirmation of renal cell carcinoma with a predominantly
papillary growth pattern.

2. Progression after standard systemic therapy or a lack of available effective
therapy, in the assessment of the Investigator.

- For salivary duct carcinoma patients, the following are required:

1. A histologic diagnosis of salivary duct carcinoma (other subtypes of salivary
gland cancer are excluded).

2. Progression after standard systemic therapy or a lack of available effective
therapy, in the assessment of the Investigator.

Exclusion Criteria:

- 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.