September 19, 2018 Page | 28 5.2.3 Trial Blinding/Masking This is an open- label trial; therefore, the Sponsor, investigator and subject will know the treatment administered. 5.3 Randomization or Treatment Allocation Not applicable 5.4 Stratification Not applicable 5.5 Concomitant Medications/Vaccinations (allowed & prohibited) Medications or vaccinations specifically prohibited in the exclusion criteria are not allowed during the ongoing trial. If there is a clinical indication for one of these or other medications or vaccinations specifically prohibited during the trial, discontinuation from trial therapy or vaccination may be required. The investigator should discuss any questions regarding this with the BMS Clinical team. The final decision on any supportive therapy or vaccina tion rests with the investigator and/or the subject's primary physician. 5.5.1 Acceptable Concomitant Medications All treatments that the investigator considers necessary for a subject’s welfare may be administered at the discretion of the investigator in keeping with the community standards of medical care. All concomitant medications received within 28 days befor e the first dose of trial treatment and 30 days after the last dose of trial treatment should be recorded. Concomitant medications administered after 30 days after the last dose of trial treatment should be recorded for SAEs and ECIs as defined in Section 7.2. 5.5.2 Prohibited Concomitant Medications Subjects are prohibited from receiving the following therapies during the Screening and Treatment Phase (including retreatment for post- complete response relapse) of this trial: • Antineoplastic systemic chemotherapy or biological therapy • Immunotherapy not specified in this protocol • Chemotherapy not specified in this protocol • Investigational agents other than Ipi-Nivo • Radiation therapy o Note: Radiation therapy to a symptomatic solitary lesion or to the brain may be allowed at the investigator’s discretion . • Live vaccines within 30 days prior to the first dose of trial treatment and while participating in the trial. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster , yellow fever, rabies, BCG, and typhoid vaccine. • Systemic glucocorticoids for any purpose other than to modulate symptoms from an event of clinical interest of suspected immunologic etiology. The use of physiologic doses of corticosteroids may be approved after consultation with the Sponsor. Protocol: Version 8.0. September 19, 2018 Page | 29 Subjects who, in the assessment by the investigator, require the use of any of the aforementioned treatments for clinical management should be removed from the trial. Subjects may receive other medications that the investigator deems to be medically necessary. The Exclusion Criteria describes other medications which are prohibited in this trial. There are no prohibited therapies during the Post- Treatment Follow -up Phase. 5.6 Rescue Medications & Supportive Care 5.6.1 Supportive Care Guidelines Subjects should receive appropriate supportive care measures as deemed necessary by the treating investigator. Suggested supportive care measures for the management of adverse events with potential immunologic etiology are outlined below and in greater detail in Section 11.6. Where appropriate, t hese guidelines include the use of oral or intravenous treatment with corticosteroids as well as additional anti- inflammatory a gents if symptoms do not improve with administration of corticosteroids. Note that several courses of steroid tapering may be necessary as symptoms may worsen when the steroid dose is decreased. For each disorder, attempts should be made to rule out other causes such as metastatic disease or bacterial or viral infection, which might require additional supportive care. The treatment guidelines are intended to be applied when the investigator determines the events to be related to Ipi-Nivo . It may be necessary to perform conditional procedures such as bronchoscopy, endoscopy, or skin photography as part of evaluation of the event. • Management of Infusion Reactions : Signs and symptoms usually develop during or shortly after drug infusion and generally resolve completely within 24 hours of completion of infusion. Table 4 below shows treatment guidelines for subject s who experience an infusion reaction associated with administration of Ipi-Nivo . Table 4 Infusion Reaction Treatment Guidelines NCI CTCAE Grade Treatment Premedication at subsequent dosing Grade 1 Mild reaction; infusion interruption not indicated; intervention not indicated Increase monitoring of vital signs as medically indicated until the subject is deemed medically stable in the opinion of the investigator. None Grade 2 Requires infusion interruption but responds promptly to symptomatic treatment (e.g., antihistamines, NSAIDS, narcotics, IV fluids); prophylactic medications indicated for < =24 hrs Stop Infusion and monitor symptoms. Additional appropriate medical therapy may include but is not limited to: IV fluids Antihistamines NSAIDS Acetaminophen Narcotics Increase monitoring of vital signs as medically indicated until the subject is deemed medically stable in the opinion of the investigator. If symptoms resolve within one hour of stopping drug infusion, the infusion may be restarted at Subject may be premedicated 1.5h (± 30 minutes) prior to infusion of IPI-NIVO OR NIVO with: Diphenhydramine 50 mg po (or equivalent dose of antihistamine). Acetaminophen 500- 1000 mg po (or equivalent dose of antipyretic). Protocol: Version 8.0. September 19, 2018 Page | 30 NCI CTCAE Grade Treatment Premedication at subsequent dosing 50% of the original infusion rate (e.g., from 100 mL/hr to 50 mL/hr). Otherwise dosing will be held until symptoms resolve and the subject should be premedicated for the next scheduled dose. Subjects who develop Grade 2 toxicity despite adequate premedication should be permanently discontinued from further trial treatme nt administration. Grades 3 or 4 Grade 3: Prolonged (i.e., not rapidly responsive to symptomatic medication and/or brief interruption of infusion); recurrence of symptoms following initial improvement; hospitalization indicated for other clinical sequelae (e.g., renal impairment, pulmonary infiltrates) Grade 4: Life-threatening; pressor or ventilatory support indicated Stop Infusion. Additional appropriate medical therapy may include but is not limited to: IV fluids Antihistamines NSAIDS Acetaminophen Narcotics Oxygen Pressors Corticosteroids Epinephrine Increase monitoring of vital signs as medically indicated until the subject is deemed medically stable in the opinion of the investigator. Hospitalization may be indicated. Subject is permanently discontinued from further trial treatment administration. No subseque nt dosing Appropriate resuscitation equipment should be available in the room and a physician readily available during the period of dr ug administration. 5.7 Diet/Activity/Other Considerations 5.7.1 Diet Subjects should maintain a normal diet unless modifications are required to manage an AE such as diarrhea, nausea or vomiting. 5.7.2 Contraception IPI-NIVO OR NIVO may have adverse effects on a fetus in utero. Furthermore, it is not known if IPI-NIVO OR NIVO has transient adverse effects on the compositio n of sperm. Non-pregnant, non- breast -feeding women may be enrolled if they are willing to use 2 methods of birth control or are considered highly unlikely to conceive. Highly unlikely to conceive is defined as 1) surgically sterilized, or 2) postmenopaus al (a woman who is ≥45 years of age and has not had menses for greater than 1 year will be considered postmenopausal), or 3) not heterosexually active for the duration of the study. The two birth control methods can be either two barrier methods or a barr ier method plus a hormonal method to prevent pregnancy. Subjects should start using birth control from study Visit 1 throughout the study period up to 120 days after the last dose of study therapy. The following are considered adequate barrier methods of contraception: diaphragm, condom (by the partner), copper intrauterine device, sponge, or spermicide. Appropriate hormonal contraceptives will include any registered and marketed contraceptive agent that contains an estrogen and/or a progestational agent (including oral, subcutaneous, intrauterine, or intramuscular agents). Protocol: Version 8.0. September 19, 2018 Page | 31 Subjects should be informed that taking the study medication may involve unknown risks to the fetus (unborn baby) if pregnancy were to occur during the study. In order to participate in the study they must adhere to the contraception requirement (described above) for the duration of the study and during the follow- up period defined in section 7.2.2- Reporting of Pregnancy and Lactation to the Sponsor and to BMS . If there is any question that a subject will not reliably comply with the requirements for contraception, that subject should not be entered into the study. 5.7.3 Use in Pregnancy If a subject inadvertently becomes pregnant while on treatment with Ipi-Nivo the subject will immediately be removed from the study. The site will contact the subject at least monthly and document the subject’s status until the pregnancy has been completed or terminated. The outcome of the pregnancy will be reported to the Sponsor and to BMS without delay and within 24 hours to the Sponsor and within 2 working days to BMS if the outcome is a serious adverse experience (e.g., death, abortion, congenital anomaly, or other disabling or life - threatening complication to the mother or n ewborn). The study investigator will make every effort to obtain permission to follow the outcome of the pregnancy and report the condition of the fetus or newborn to the Sponsor. If a male subject impregnates his female partner the study personnel at the site must be informed immediately and the pregnancy reported to the Sponsor and to BMS and followed as described above and in Section 7.2.2. 5.7.4 Use in Nursing Women It is unknown whether Ipi-Nivo is excreted in human milk. Since many drugs are excreted i n human milk, and because of the potential for serious adverse reactions in the nursing infant, subjects who are breast -feeding are not eligible for enrollment. 5.8 Subject Withdrawal/Discontinuation Criteria Subjects may withdraw consent at any time for any r eason or be dropped from the trial at the discretion of the investigator should any untoward effect occur. In addition, a subject may be withdrawn by the investigator or the Sponsor if enrollment into the trial is inappropriate, the trial plan is violated , or for administrative and/or other safety reasons. Specific details regarding discontinuation or withdrawal are provided in Section 7.1.4 – Other Procedures. A subject must be discontinued from the trial for any of the following reasons: • The subject or legal representative (such as a parent or legal guardian) withdraws consent. • Confirmed radiographic disease progression Note : For unconfirmed radiographic disease progression, please see Section 5.2.2 Note : A subject may be granted an exception to continue on treatment with confirmed radiographic progression if clinically stable or clinically improved, please see Section 7.1.2.7.1 • Unacceptable adverse experiences as described in Section 5.2.1.2 Protocol: Version 8.0. September 19, 2018 Page | 32 • Intercurrent illness that prevents further administration of tr eatment • Investigator’s decision to withdraw the subject • The subject has a confirmed positive serum pregnancy test • Noncompliance with trial treatment or procedure requirements • The subject is lost to follow -up • Administrative reasons The End of Treatment and Follow- up visit procedures are listed in Section 6 (Protocol Flow Chart) and Section 7.1.5 (Visit Requirements). After the end of treatment, each subject will be followed for 30 days for adverse event monitoring (serious adverse events will be collected for 90 days after the end of treatment as described in Section 7.2.3.1). Subjects who discontinue for reasons other than progressive disease will have post -treatment follow - up for disease status until disease progression, initiating a non- study cancer tre atment, withdrawing consent or becoming lost to follow -up. After documented disease progression each subject will be followed by telephone for overall survival until death, withdrawal of consent, or the end of the study, whichever occurs first. 5.8.1 Discontinu ation of Study Therapy after CR Discontinuation of treatment may be considered for subjects who have attained a confirmed CR that have been treated for at least 24 weeks with maintenance Nivo and had at least two treatments with Nivo beyond the date when the initial CR was declared. Subjects who then experience radiographic disease progression may be eligible for up to one year of additional treatment with Ipi-Nivo (similar schedule) via the Second Course Phase at the discretion of the investigator if no cancer treatment was administered since the last dose of Ipi-Nivo or Nivo, the subject meets the safety parameters listed in the Inclusion/Exclusion criteria, and the trial is open. Concomitant administration of the Ad.p53 -DC vaccine together with Ipi-Nivo or Nivo is desired and included as part of the Second Course Phase described above if feasible from a medical and logistical point of view . 5.9 Subject Replacement Strategy Subjects deemed not eligible will be replace and will not count towards achieving the trial sample size calculation 5.10 Clinical Criteria for Early Trial Termination Early trial termination will be the result of the criteria specified below: 1. Quality or quantity of data recording is inaccurate or incomplete 2.