Overview

A Study of Pembrolizumab in Patients With Relapsed Or Metastatic Osteosarcoma Not Eligible for Curative Surgery

Status:
Terminated
Trial end date:
2019-01-31
Target enrollment:
0
Participant gender:
All
Summary
This is a phase II, single arm, open-label, interventional trial of pembrolizumab (MK-3475) in patients with osteosarcoma who have experienced disease relapse or progression after at least one line of systemic treatment, and who are not eligible for curative surgery.
Phase:
Phase 2
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
Oslo University Hospital
Collaborators:
Italian Sarcoma Group
Merck Sharp & Dohme Corp.
Treatments:
Pembrolizumab
Criteria
Inclusion Criteria:

1. Histologically confirmed osteosarcoma.

2. Disease relapse or progression after at least one line of systemic treatment.

1. First-line systemic treatment should include cytotoxic chemotherapy according to
local practice.

2. The patient can be eligible if he/she is considered medically unfit for
chemotherapy, as assessed by the sarcoma centre in charge of the patient's
treatment.

3. Surgical resection with curative intent not possible.

4. Be willing and able to provide written informed consent/assent for the trial.

5. Be >18 years of age on day of signing informed consent.

6. Have measurable disease based on RECIST, version 1.1.

7. Be willing to provide tissue from a newly obtained core or excisional biopsy of a
tumor lesion. Newly-obtained is defined as a specimen obtained up to 6 weeks (42 days)
prior to initiation of treatment on Day 1. Subjects for whom newly-obtained samples
cannot be provided (e.g. inaccessible or subject safety concern) may submit an
archived specimen.

8. Have a performance status of 0 or 1 on the ECOG Performance Scale.

9. Demonstrate adequate organ function as defined in Table 1, all screening labs should
be performed within 10 days of treatment initiation.

10. Female subject of childbearing potential should have a negative urine or serum
pregnancy within 72 hours prior to receiving the first dose of study medication. If
the urine test is positive or cannot be confirmed as negative, a serum pregnancy test
will be required.

11. Female subjects of childbearing potential should be willing to use 2 methods of birth
control or be surgically sterile, or abstain from heterosexual activity for the course
of the study through 120 days after the last dose of study medication (Reference
Section 5.7.2). Subjects of childbearing potential are those who have not been
surgically sterilized or have not been free from menses for > 1 year.

12. Male subjects should agree to use an adequate method of contraception starting with
the first dose of study therapy through 120 days after the last dose of study therapy.

Exclusion Criteria:

1. Is currently participating and receiving study therapy or has participated in a study
of an investigational agent and received study therapy or used an investigational
device within 4 weeks of the first dose of treatment.

2. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any
other form of immunosuppressive therapy within 7 days prior to the first dose of trial
treatment.

3. Has a known history of active TB (Bacillus Tuberculosis)

4. Has a history of (non-infectious) pneumonitis that required steroids or current
pneumonitis.

5. Hypersensitivity to pembrolizumab or any of its excipients.

6. Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study
Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events
due to agents administered more than 4 weeks earlier.

7. Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy
within 2 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at
baseline) from adverse events due to a previously administered agent.

- Note: Subjects with ≤ Grade 2 neuropathy are an exception to this criterion and
may qualify for the study.

- Note: If subject received major surgery, they must have recovered adequately from
the toxicity and/or complications from the intervention prior to starting
therapy.

8. Has a known additional malignancy that is progressing or requires active treatment.
Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the
skin that has undergone potentially curative therapy or in situ cervical cancer.

9. Has known active central nervous system (CNS) metastases and/or sarcomatous
meningitis. Subjects with previously treated brain metastases may participate provided
they are stable (without evidence of progression by imaging for at least four weeks
prior to the first dose of trial treatment and any neurologic symptoms have returned
to baseline), have no evidence of new or enlarging brain metastases, and are not using
steroids for at least 7 days prior to trial treatment. This exception does not include
sarcomatous meningitis which is excluded regardless of clinical stability.

10. Has active autoimmune disease that has required systemic treatment in the past 2 years
(i.e. with use of disease modifying agents, corticosteroids or immunosuppressive
drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid
replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a
form of systemic treatment.

11. Has known history of, or any evidence of active, non-infectious pneumonitis.

12. Has an active infection requiring systemic therapy.

13. Has a history or current evidence of any condition, therapy, or laboratory abnormality
that might confound the results of the trial, interfere with the subject's
participation for the full duration of the trial, or is not in the best interest of
the subject to participate, in the opinion of the treating Investigator.

14. Has known psychiatric or substance abuse disorders that would interfere with
cooperation with the requirements of the trial.

15. Is pregnant or breastfeeding, or expecting to conceive or father children within the
projected duration of the trial, starting with the pre-screening or screening visit
through 120 days after the last dose of trial treatment.

16. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.

17. Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).

18. Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA
[qualitative] is detected).

19. Has received a live vaccine within 30 days of planned start of study therapy. Note:
Seasonal influenza vaccines for injection are generally inactivated flu vaccines and
are allowed; however intranasal influenza vaccines (e.g., Flu-Mist) are live
attenuated vaccines, and are not allowed.