A Study of CDX-1127 (Varlilumab) in Patients With Select Solid Tumor Types or Hematologic Cancers

CDX-1127 is a fully human monoclonal antibody that binds to a molecule called CD27 found on
certain immune cells and also on certain hematologic tumor cells and may act to promote
anti-tumor effects.

This study will evaluate the safety and activity of escalating doses of CDX-1127 in patients
with B-cell and T-cell hematologic malignancies known to express CD27 and solid tumors that
are more likely to be responsive to the immune system.

Eligible patients who enroll in the dose escalation portion of the study will be assigned to
one of 5 dose levels of CDX-1127. This first phase of the study will test the safety profile
of CDX-1127 and will assess which dose to test in future studies.

During the Expansion phase, cohorts of approximately 15 patients each will receive the study
treatment to continue to evaluate the safety profile of CDX-1127 and to determine if it has
an effect on their cancer. Expansion cohorts may be limited to one or more tumor types.

Patients enrolled in the study may receive study treatment for up to 5 cycles, until their
disease has progressed or until it is necessary to stop the treatment for safety or other
reasons.

All patients enrolled in the study will be closely monitored to determine if their cancer is
responding to treatment and for any side effects that may occur.

Inclusion Criteria:

Among other criteria, patients must meet the following conditions to be eligible for the
study:

1. 18 years of age or older.

2. Body Weight ≤ 120 kg.

3. Histologic diagnosis of either a B-cell or T-cell hematologic malignancy known to
express CD27 or one of the following solid tumors: metastatic melanoma, renal (clear)
cell carcinoma, hormone-refractory prostate adenocarcinoma, ovarian cancer, colorectal
adenocarcinoma or non-small cell lung cancer. For the solid tumor expansion cohorts,
enrollment is limited to the following solid tumors: melanoma and renal cell
carcinoma.

4. Tumor must be recurrent or treatment refractory with no remaining alternative,
approved therapy options, with the following exception: melanoma patients enrolled in
the expansion phase must have previously received ipilimumab and, for patients with
the BRAF V600E mutation, vemurafenib, or have been offered such therapies and refused,
and patients must have progressive disease subsequent to previous therapies.

5. Measurable or evaluable disease.

6. Have adequate blood, bone marrow, liver and kidney function as determined by
laboratory tests.

7. If of childbearing potential (male or female), agree to practice an effective form of
contraception during study treatment.

8. Have little or no side effects remaining from prior cancer therapies.

9. Provide written informed consent.

Exclusion Criteria:

Among other criteria, patients who meet the following conditions are NOT eligible for the
study:

1. Known prior primary or metastatic brain or meningeal tumors.

2. Receiving treatment with immunosuppressive agents, including any systemic steroids.

3. Active infection requiring systemic therapy, known HIV infection, or positive test for
hepatitis B surface antigen or hepatitis C.

4. Is being treated for anti-coagulation (i.e. warfarin) for reasons other than catheter
patency.

5. Women who are pregnant or lactating.

6. Prior allogeneic bone marrow transplant.

7. Autologous bone marrow transplant within 100 days of first dosing.

8. Recent chemotherapy or other anti-cancer therapy (within 2 - 14 weeks depending on
treatment type).

9. Systemic radiation therapy within 4 weeks or prior focal radiotherapy within 2 weeks
prior to first dosing.