First-in-human, open-label, dose-escalation trial with expansion cohorts to evaluate safety of Axl-specific antibody-drug conjugate (enapotamab vedotin- HuMax-AXL-ADC) in patients with solid tumors

The purpose of the trial is to determine the maximum tolerated dose and to establish the
safety profile of HuMax-AXL-ADC in a mixed population of patients with specified solid tumors

Inclusion Criteria:

1. For the dose escalation part: Patients with selected, relapsed or refractory solid
tumors who have failed available standard therapy or who are not candidates for
standard therapy. For the expansion part: Patients with advanced and/or metastatic
solid tumors who are not candidates for standard therapy

2. Patients must have measurable disease according to Response Evaluation Criteria In
Solid Tumors (RECIST).

3. For the expansion patients must provide a tumor tissue sample from archival tissue or
fresh biopsy at enrolment

4. Age ≥ 18 years.

5. Acceptable renal function

6. Acceptable liver function

7. Acceptable hematological status

8. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

9. Life expectancy of at least three months.

10. Patients, both females and males, of childbearing/reproductive potential must agree to
use adequate contraception while included in the trial and for six months after the
last infusion of HuMax-AXL-ADC

11. Patients must provide a signed informed consent form before any trial relates
activities are carried out.

Exclusion Criteria:

1. Acute deep vein thrombosis or clinically relevant pulmonary embolism, not stable for
at least 4 weeks prior to first IMP administration.

2. Have clinically significant cardiac disease

3. Known congestive heart failure and/ or a known decreased cardiac ejection fraction of
< 45%. A baseline QT interval as corrected by Fridericia's formula (QTcF) > 480 msec,
a complete left bundle branch block (defined as a QRS interval ≥ 120 msec in left
bundle branch block form) or an incomplete left bundle branch block.

4. Uncontrolled hypertension

5. Have received granulocyte colony stimulating factor (G-CSF) or granulocyte/macrophage
colony stimulating factor support 3 weeks prior to first IMP administration.

6. Have received a cumulative dose of corticosteroid > 150 mg prednisone (or equivalent
doses of corticosteroids) within two weeks before the first Investigational Medicinal
Product (IMP) administration.

7. History of ≥ grade 3 allergic reactions to monoclonal antibody therapy as well as
known or suspected allergy or intolerance to any agent given in the course of this
trial.

8. Major surgery within four weeks before first IMP administration.

9. Any history of intracerebral arteriovenous malformation, cerebral aneurysm, brain
metastases or stroke.

10. Any anticancer therapy including; small molecules, immunotherapy, chemotherapy
monoclonal antibodies or any other experimental drug within five half-lives but
maximum four weeks before first infusion. Accepted exceptions are bisphosphonates,
denosumab and gonadotropin-releasing hormone agonist or antagonist.

11. Prior therapy with a conjugated or unconjugated auristatin derivative/vinca-binding
site targeting payload.

12. Radiotherapy within 14 days prior to first IMP administration.

13. Known past or current malignancy other than inclusion diagnosis, except for:

- Cervical carcinoma of Stage 1B or less.

- Non-invasive basal cell or squamous cell skin carcinoma.

- Non-invasive, superficial bladder cancer.

- Prostate cancer with a current prostate specific antigen (PSA) level < 0.1 ng/mL.

- Breast cancer in BRCA1 or BRCA2 positive ovarian cancer patients.

- Any curable cancer with a complete response (CR) of > 2 years duration.

14. Melanoma patients with an lactate dehydrogenase (LDH) ≥ 3 x upper limit normal (ULN).

15. Ongoing significant, uncontrolled medical condition including:

o Serious, non-healing wound, skin ulcer (of any grade), or bone fracture.

16. Grade 2 or higher peripheral neuropathy.

17. Clinically significant active viral, bacterial or fungal infection

18. Known human immunodeficiency virus seropositivity.

19. Known positive serology for hepatitis B (unless due to vaccination or passive
immunization due to immunoglobulin therapy)

20. Known positive serology for hepatitis C (unless due to immunoglobulin therapy)

21. Substance abuse, medical, psychological or social conditions that may interfere with
the patient's participation in the trial or evaluation of the trial result

22. History of organ allograft (except for corneal transplant) or autologous or allogeneic
bone marrow transplant, or stem cell rescue within 3 months prior to the first dose of
IMP

23. Body weight < 40 kg

24. Women who are pregnant or breast feeding.

25. Pulmonary hemorrhage or hemoptysis > 2.5 ml blood within 6 weeks unless cause has been
addressed and is medically resolved.

26. History of acute pneumonitis.