Iovance Alliance: LN-145 Across Multiple Tumor Types

Tumor Sample Collection:

If you are found to be eligible to take part in this study, you will have surgery to remove a
piece of the tumor. The study doctor will discuss this procedure in more detail with you and
you will sign a separate consent form explaining the procedure and its risks. You may be
admitted to the hospital for this procedure. After the tumor tissue is collected, the sample
will be sent to a facility chosen by lovance Biotherapeutics (a company supporting this
study) (. At the facility, T-cells will be separated from the tissue and then grown in the
facility to create LN-145. This process may take up to 6 weeks. If enough cells cannot be
collected or they cannot be grown in the facility, you will not be able to be treated in this
study, and other treatment options will be discussed with you. However, you will continue to
take part in this study as part of long-term follow-up (described below).

Study Drug Administration:

If LN-145 can successfully be created in the facility, you will be hospitalized and begin to
receive chemotherapy (cyclophosphamide and fludarabine) to help prepare your body to receive
LN-145.

Negative days are days before your LN-145 infusion. Day 0 is the day of your LN- 145
infusion. Positive days are the days after the LN-145 infusion.

To receive the study drugs, you may be asked to have a central venous catheter (CVC) placed.
A CVC is a sterile flexible tube that will be placed into a large vein while you are under
local anesthesia. Your doctor will explain this procedure to you in more detail, and you will
be required to sign a separate consent form.

You will receive cyclophosphamide by vein over about 2 hours on Days -7 and -6. You will also
receive mesna by vein continuously (non-stop) on these days. On Days -5 through -1, you will
receive fludarabine by vein over about 30 minutes every day.

On Day 0, you will receive LN-145 by vein over about 45 minutes.

After you receive LN-145, you will receive interleukin-2 (IL-2) by vein over about 30 minutes
up to 6 times over Days 1-4. IL-2 helps LN-145 to "attack" the tumor. Your dose of IL-2 may
change while you are on study.

You may be given standard drugs to help decrease the risk of side effects. You may ask the
study staff for information about how the drugs are given and their risks.

You will stay in the hospital for at least 1 week but you may stay in the hospital for as
long as the doctor thinks it is needed. You will be discharged from the hospital when the
doctor thinks it is safe for you to do so. Length of Study

You may receive up to 11 days of chemotherapy and 1 infusion of LN-145. You will no longer be
able to take the study drug(s) if the disease gets worse, if intolerable side effects occur,
or if you are unable to follow study directions. Your participation on the study will be over
after at least 3 years of follow-up.

Study Visits:

On the day of the tumor sample collection:

- Blood (about 4½ tablespoons) will be drawn for routine and immune system testing. This
sample will also be used to learn if you have human papillomavirus (HPV).

- Urine will be collected for routine tests.

One (1) time between Day -21 and Day -14:

- You will complete a questionnaire about how you are feeling. It should take about 15
minutes to complete.

- You will have a physical exam.

- Blood (about 1 tablespoon) and urine will be collected for routine tests. If you can
become pregnant, part of this blood sample will be used for a pregnancy test.

- You will have imaging scans.

On Days -7 through Day 4:

- You will have a physical exam every day, if the doctor thinks it is needed.

- Blood (about 1 tablespoon) and urine will be collected every day for routine tests, if
the doctor thinks it is needed.

- On Day -7 only, blood (about 3½ tablespoons) will be drawn for immune system testing.

On Days 14, 28, 42 (Week 6), and 84 (Week 12):

- You will have a physical exam.

- Blood (about 4½ tablespoons) will be drawn for routine and immune system testing to
learn how LN-145 has affected the disease.

- Urine will be collected for routine tests.

- On Day 42 only, you will have a biopsy for research tests, including genetic testing.
This research will help researchers understand how and why you responded to the study
drug and if your genetic information (DNA) influenced your response to the drug. The
study doctor will tell you what type of biopsy you will have.

- On Days 42 and 84 only, you will have imaging scans, and some of your blood will be used
for biomarker testing.

- On Day 84 only, you will complete a questionnaire about how you are feeling.

Early Withdrawal Visit:

If you choose to leave the study early, you may be asked to return to the clinic for a final
visit. At this visit:

- You will have a physical exam.

- Blood (about 4½ tablespoons) will be drawn for routine and immune system testing to
learn how LN-145 has affected the disease.

- Urine will be collected for routine tests.

- You will have imaging scans.

You will also continue to take part in the Long-Term Follow-Up part of the study.

Follow-Up:

At Week 18 and then Months 6, 9, 12, 18, and 24 after your dose of LN-145, you will have
follow-up visits. At each visit:

- You will have a physical exam.

- You will have imaging scans.

- Blood (about 1 tablespoon) will be drawn to test for biomarkers.

- At Week 18 and Month 6 only, blood (about 1 tablespoon) and urine will be collected for
routine tests.

- At Months 6, 9, and 12 only, blood (about 3½ tablespoons) will be drawn for immune
system testing.

- At Months 6, 12, and 24 only, you will complete a questionnaire about how you are
feeling.

Long-Term Follow-Up:

After Month 24, you will be called by the study staff every 3 months for at least 3 years to
learn if the disease has gotten worse or better and if you have started a new cancer
treatment. Each call should last about 5-10 minutes.

Inclusion Criteria:

1. Age between 18 and 70 (Subjects aged 16-70 may be enrolled into the osteosarcoma
cohort).

2. Subjects must be willing and able to provide informed consent. For patients < 18 years
of age, their parents or legal guardians must sign a written informed consent. Assent,
when appropriate, will be obtained according to institutional guidelines.

3. Clinical performance status of ECOG 0 or 1 at enrollment and within 7 days of
initiating lymphodepleting chemotherapy.

4. Subjects must have an area of tumor amenable to excisional biopsy for the generation
of TIL separate from, and in addition to, a target lesion to be used for response
assessment.

5. Any prior therapy directed at the malignant tumor, including radiation therapy,
chemotherapy, and biologic/targeted agents must be discontinued at least 28 days prior
to tumor resection for preparing TIL therapy.

6. Within 7 days of enrollment and with 24 h of starting lymphodepleting chemotherapy,
subjects must meet the following laboratory criteria: Absolute neutrophil count (ANC)
>/= 1000/mm^3; Hemoglobin >/= 9.0 g/dL (transfusion allowed); Platelet count >/=
100,000/mm^3; ALT/SGPT (alanine aminotransferase) and AST/SGOT (aspartate
aminotransferase) metastases may have liver function tests [LFT] clearance (Cockcroft-Gault) >/= 50.0 mL/min; Total bilirubin Prothrombin Time (PT) & Activated Partial Thromboplastin Time (aPTT) (correction with vitamin K allowed) unless subject is receiving anticoagulant therapy
(which should be managed according to institutional norms prior to and after
excisional biopsy); Negative serum pregnancy test (female subjects of childbearing
potential).

7. Subjects must not have a confirmed human immunodeficiency virus (HIV) infection.

8. Subjects must have a 12-lead electrocardiogram (EKG) showing no active ischemia and
Fridericia's corrected QT interval (QTcF) less than 480 ms.

9. Subjects 40 years of age and older must also have a negative stress cardiac test (i.e.
EKG stress test, stress thallium, dobutamine echocardiogram or other stress test that
will rule out cardiac ischemia). Stress test may be required of subjects less than 40
years of age if warranted by family history or risk factors by the treating
investigator.

10. Subjects of childbearing potential must be willing to practice an approved highly
effective method of birth control starting at the time of informed consent and for 1
year after the completion of the lymphodepletion regimen. Approved methods of birth
control are as follows: Hormonal contraception (i.e. birth control pills, injection,
implant, transdermal patch, vaginal ring); Intrauterine device (IUD); Tubal Ligation
or hysterectomy; Subject/partner status post vasectomy; Implantable or injectable
contraceptives; and Condoms plus spermicide.

11. Able to adhere to the study visit schedule and other protocol requirements.

12. Pulmonary function tests (spirometry) demonstrating forced expiratory value (FEV) 1
greater than 65% predicted or forced vital capacity (FVC) greater than 65% of
predicted.

13. Ovarian cancer cohort only: Subjects must have high-grade non-mucinous histology
(carcinosarcomas are allowed).

14. Ovarian cancer cohort only: Subjects must have platinum refractory or resistant
disease.

15. Osteosarcoma cohort only: Subjects with osteosarcomas must have relapsed or become
refractory to conventional therapy and have received a regimen including some
combination of high-dose methotrexate, doxorubicin, cisplatin, and/or ifosfamide.

16. Other bone and soft tissue sarcomas cohort only: Subjects with dedifferentiated
chondrosarcomas, dedifferentiated giant cell tumor of bone, giant cell tumor of bone,
undifferentiated pleomorphic sarcoma of bone, or high-grade unclassified sarcomas of
bone must have received at least one prior line of therapy unless no standard
first-line therapy exists in which case enrollment as initial therapy is allowed.

17. Other bone and soft tissue sarcomas cohort only: Subjects with other soft tissue
sarcomas who have received at least one line of therapy.

Exclusion Criteria:

1. Active systemic infections requiring intravenous antibiotics, coagulation disorders or
other major medical illnesses of the cardiovascular, respiratory or immune system. PI
or his/her designee shall make the final determination regarding appropriateness of
enrollment.

2. Patients with active viral hepatitis

3. Patients who have a left ventricular ejection fraction (LVEF) < 45% at Screening.

4. Patients with a history of prior adoptive cell therapies.

5. Persistent prior therapy-related toxicities greater than Grade 2 according to Common
Toxicity Criteria for Adverse Events (CTCAE) v4.03, except for peripheral neuropathy,
alopecia, or vitiligo prior to enrollment.

6. Primary immunodeficiency.

7. History of organ or hematopoietic stem cell transplant.

8. Chronic steroid therapy, however prednisone or its equivalent is allowed at mg/day.

9. Patients who are pregnant or nursing.

10. Presence of a significant psychiatric disease, which in the opinion of the principal
investigator or his/her designee, would prevent adequate informed consent.

11. History of clinically significant autoimmune disease including active, known, or
suspected autoimmune disease. Subjects with resolved side effects from prior
checkpoint inhibitor therapy, vitiligo, psoriasis, type 1 diabetes or resolved
childhood asthma/atopy would be an exception to this rule. Subjects that require
intermittent use of bronchodilators or local steroid injections would not be excluded.
Subjects with hypothyroidism stable on hormone replacement or Sjorgen's syndrome will
not be excluded.

12. History of clinically significant chronic obstructive pulmonary disease (COPD),
asthma, or other chronic lung disease.

13. History of a second malignancy (diagnosed in the last 5 years). Exceptions include
basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ
cervical cancer that has undergone potentially curative therapy.

14. History of known active central nervous system metastases and/or carcinomatous
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 initiation of lymphodepletion.

15. Has received a live vaccine within 30 days prior to the initiation of lymphodepletion.

16. Any other condition that in the investigator's judgement would significantly increase
the risks of participation.