Dose level allocation will be performed by the sponsor after participants have given their written informed consent and have completed the necessary baseline assessments. The site staff will email a completed Registration Form to the designated sponsor study team member . The sponsor will assign a participant identification number documenting participant enrollment. No participant shall receive investigational product until the investigator or designee has received the following information in writing from th e sponsor: Confirmation of the participant’s enrollment; Specification of the dose level for that participant; Permission to proceed with dosing the participant. The sponsor or designee will notify the other sites of the inclusion of a new participant, an d will inform study sites about the next possible enrollment date. 5.2. Participant Compliance All doses of adenovirus, pDNA, tremelimumab and sasanlimab will be administered by the appropriatel y designated study staff at the investigational site. The site will complete the required dosage Preparation Record located in the Investigational Product manual. The use of the Preparation Record is preferred but it does not preclude the use of an existing appropriate clinical site documentation sy stem. The existing clinical site’s documentation system should capture all pertinent/required information on the preparation and administration of the dose. This may be used in place of the Preparation Record after approval from the Pfizer monitor. Participants who fail to comply with the study requirements may be withdrawn from the study . PF-06936308 C3621001 Final Protocol Amendment 2, 22 Dec 2020 PFIZER CONFIDENTIAL Page 775.3.Investigational Product Supplies All components of VBI R-2 will be supplied by Pfizer. VBIR-2 consists of the following components: Adenovirus (AdC68), plasmid DNA (pDNA), tremelimumab and sasanlimab . Sites will be provided with the following supplies: PF- 06871923 AdC68 Solution for Injection 3 x 1011VP/mL; PF-06871925 pDNA Soluti on for Injection 2.5 mg/mL ; PF-06753388 Tremelimumab Solution for Injection 100 mg/mL ; TDS -IM V 2.0 electroporation device and associated supplies (eg, cartridges) for pDNA administration; PF-06801591 Sa sanlimab Solution for I njection 50 mg/mL . Study centers will receive a suppl y of clinical trial materials upon site activation with instructions on how to confirm drug receipt. Resupplies will be made during the course of the study based on need. Study centers will supply commonl y available sterile s yringes and needs for IM and SC administration. The details on drug suppl y will be provided in the Investigational Product Manual (IP Manual). The study monitor should be contacted for any issues related to drug supplies. 5.3.1. Dosage Form(s) and Packaging PF-06871923 AdC68 Solution for Injection is presented as a sterile solution for intramuscular administration. Each vial contains AdC68 at 3x 1011VP/mL in an aqueous buffered solution. Each vial is filled with an adequate volume to eject a minimum 1.0 mL fr om a s yringe with an IM needle attached. The vial is sealed with a stopper and an overseal and labeled according to local regulatory requirements. Two vials will be dispensed per participant, regardless of dose, to facilitate bilateral injection. PF-06871925 pDNA Solution for Injection, 2.5 mg/mL, is presented as a sterile solution for intramuscular administration. Each glass prefilled sy ringe (PFS) contains pDNA at 2.5mg/mL in aqueous buffered solution. The PFS is filled with an adequate volume to eje ct 1.0mL when administered using the TDS - IM V 2.0 electroporation device. The PFS is sealed with a plunger stopper and a tip cap and labeled according to local regulatory requirements. Two (2) prefilled s yringes will be dispensed per participant. Each TDS -IM V 2.0 6mm Application cartridge, for unique use, for intramuscular administration of the pDNA solution will be supplied in a sterile tray (one cartridge/tray ) labeled according to local regulatory requirements. PF-06753388 Tremelimumab Solution for I njection is presented as a sterile solution. Each vial contains tremelimumab at 100 mg/mL in aqueous buffered solution. The vial is filled with an adequate volume to eject a minimum 0.75 mL from a s yringe with a SC needle PF-06936308 C3621001 Final Protocol Amendment 2, 22 Dec 2020 PFIZER CONFIDENTIAL Page 78attached. The vial is sealed with a stopper and an overseal and labeled according to local regulatory requirements. Two vials will be dispensed per participant, regardless of dose, to facilitate bilateral injection. PF-06801591 Sasanlimab Solution for I njection 50 mg/mL is presented as a sterile solution. Each vial contains 100 mg of sasanlimab in 2mL of aqueous buffered solution, and contains a sufficient amount to ensure an extractable volume of 2 mL. Each vial is sealed with a stopper and an overseal, and labeled according to loca l regulatory requirements. 5.3.2. Preparation and Dispensing AdC68, tremelimumab and sasanlimab are provided as single use vials; pDNA is provided as a single use prefilled sy ringe. They will be packaged and dispensed in cartons with tamper evident seals. The c artons should not be opened until the drug is to be administered. For the adenovirus, pDNA, tremelimumab and sasanlimab , see the Investigational Product (I P) manual and the TDS -IM V 2.0 Instructions for Use for instructions on how to prepare the investiga tional products for administration. The TDS -IM v2.0 6mm Application cartridges for the administration of the plasmid are provided for single use, and will be packaged and dispensed in cartons with tamper evident seals. The cartons should not be opened unt il the time of administration. Investigational product should be prepared and dispensed b y an appropriately qualified and experienced member of the study staff (eg, physician, nurse, phy sician’s assistant, nurse practitioner, pharmacy assistant/technician, or pharmacist) as allowed b y local, state, and institutional guidance. Only qualified personnel who are familiar with procedures that minimize undue exposure to themselves and to the environment should undertake the preparation, handling, and safe disposal of biologic agents. 5.4.Administration All AdC68 intramuscular injections are given bilaterall y. AdC68 will be administered on Day 1of Cycles 1 and 2. Please refer to the IP manual for full instructions on the dosage and administration. Plasmid DNA intr amuscular injections are given bilaterally . pDNA will be administered beginning on Day 29of Cy cles 1 and 2 and will then be given at 4 week intervals. After Cycle 2, pDNA will continue to be administered every 2months in the Maintenance Treatment Perio d. Please refer to the IP manual for full instructions on the dosage and administration of the pDN A and to the TDS -IM V 2.0 Instructions for Use document for the set up and use of the electroporation device. The TDS- IM device should be operated by clinic al personnel that have completed the necessary training on device operation. PF-06936308 C3621001 Final Protocol Amendment 2, 22 Dec 2020 PFIZER CONFIDENTIAL Page 79All IM injections (AdC68 and pDNA) will be given bilaterally in the deltoid muscles or in the vastus lateralis muscles of the quadriceps. Preference should be given to the vastus lateralis muscles when possible. Tremelimumab will be administered bilaterall y subcutaneousl y at 4 week intervals during Cycles 1 and 2 on the same day as the AdC68 or pDNA dosing as described in the SCHEDUL E OF ACTIVITIES . After C ycle 2, tremelimumab will continue to be administered every 2 months in the Maintenance Treatment Period. Both AdC68 and pDNA injections should be given prior to tremelimumab administration. Please refer to the IP manual for full instructions on the dosage and administration of tremelimumab. Tremelimumab is to be administered in close proximity to the vaccination site. If the vaccination is administered in the vastus lateralis, the tremelimumab is to be administered SC in either the lower quadrants of the abdomen or the quadriceps. If the vaccination is administered in the deltoid, the tremelimumab is to be administered SC bilaterall y in the outer triceps. Sasanlimab will be administered bilaterally subcutaneously at 4 week intervals on the same day as the AdC68 or pDNA and tremelimumab during C ycles 1 and 2 as described in the SCHEDUL E OF ACTIVITIES . The AdC68 or pDNA as well as the treme limumab doses should be given prior to sasanlimab administration. During the Maintenance Treatment Period, participants will continue to be dosed with sasanlimab at monthly intervals until confirmed disease progression per RECI ST. Please refer to the IP manual for full instructions on the dosage and administration of sasanlimab . Sasanlimab is to be administered in close proximity to the vaccination site. I f the vaccination is administered in the vastus lateralis, the sasanlimab is to be administered SC bilaterall y in the lower quadrants of the abdomen. If the vaccination is administered in the deltoid, the sasanlimab is to be administered SC bilaterally in the outer triceps. 5.4.1. Recommended Dose Modifications Every effort should be made to administer invest igational product on the planned dose and schedule. In the event of significant toxicity , dosing may be delay ed and/or reduced as described below. In the event of multiple toxicities, dose modification should be based on the worst toxicity observed. Part icipants are to be instructed to notify investigators at the first occurrence of an y adverse sy mptom. Dose modifications may occur in one of three ways: Within a cy cle: dosing interruption until adequate recovery and dose reduction, if required, during a g iven treatment cy cle; Between cy cles: next cy cle administration may be delay ed due to persisting toxicity when a new cy cle is due to start; PF-06936308 C3621001 Final Protocol Amendment 2, 22 Dec 2020 PFIZER CONFIDENTIAL Page 80In the next cycle: dose reduction may be required in a subsequent cy cle based on toxicity experienced in the previo us cy cle. 5.4.2. Dosing Interruptions/Delays due to Treatment Related Toxicity Participants experiencing Grade 3or 4potentially treatment related toxicity or intolerable Grade 2toxicity despite supportive care should have their treatment with all of the components interrupted/delay ed. Appropriate follow -up assessments should be done until adequate recovery occurs as assessed b y the investigator. Re-treatment following treatment interruption for treatment related toxicity or at the start of any new cy cle may not occur until all of the following parameters have been met: ANC 1,000/mm3. Platelets count 50,000/mm3. Non-hematologic toxicities have returned to baseline or Grade 1severity (or, at the investigator discretion, Grade 2if not considered a sa fety risk for the participant). If a treatment delay results from worsening of hematologic or biochemical parameters, the frequency of relevant blood tests should be increased as clinicall y indicated. 5.4.3. If these conditions are met within 2 weeks of treatment interruption or cycle delay, investigational product(s) may be resumed. Refer to section Dosing Interruptions/Delays due to Non- Related Events If participants require treatment interruption for reasons other than treatment -related toxicity (eg, surgery ) lasting >4weeks, treatment resumption should be decided in consultation with the Sponsor. In the event of active SARS -CoV2 infection confirmed (positive by regulatory authority - approved test) or presumed (test pending/clinical suspicion), the following criteria apply : For s ymptomatic participants with active SARS -CoV2 infection, investigational treatment should be delayed for at least 14 day s from start of sy mptoms. This delay is intended to allow resolution of sy mptoms of SARS -CoV2 infection. Prior to restarting treatment, the participants should be afebrile for 72 hours and SARS -CoV2- related s ymptoms should have recovered to ≤Grade 1 for a m inimum of 72 hours. Discuss with the Sponsor prior to restarting treatment. Consider potential drug -drug interactions (as described per stud y protocol) for an y concomitant medication administered for treatment of SARS -CoV2 infection. PF-06936308 C3621001 Final Protocol Amendment 2, 22 Dec 2020 PFIZER CONFIDENTIAL Page 81Dose Reductions for adverse events requiring dose reduction at the time of treatment resumption. If these conditions are not met, treatment resumption must be delay ed up to a maximum of 2 weeks. If these parameters have not been met after 2 weeks of dosing interruption or 2weeks of new cy cle delay , permanent discontinuation of treatment should be considered. Treatment resumption for participants recovering from treatment -related toxicity after >2weeks of treatment interruption or cy cle delay may be considered onl y if the participant is deemed to be deriving obvious clinical benefit per the investigator’s best medical judgment and needs to be agreed between the investigator and the sponsor . 5.4.4. Dosing Interruptions/Delays due to Non -Related Events If participants require treatment interruption for reasons other than treatment -related toxicity (eg, surgery ) lasting >4weeks, treatment resumption should be decided in consultation with the Sponsor . In the event of active SARS -CoV2 infection confirmed (positive by regulatory authority -approved test) or presumed (test pending/clinical suspicion), the following criteria apply : For s ymptomatic participants with active SARS -CoV2 infection, investigat ional treatment should be delayed for at least 14 day s from start of sy mptoms. This delay is intended to allow resolution of sy mptoms of SARS -CoV2 infection. Prior to restarting treatment, the participants should be afebrile for 72 hours and SARS -CoV2- related s ymptoms should have recovered to ≤Grade 1 for a minimum of 72 hours. Discuss with the Sponsor prior to restarting treatment. Consider potential drug -drug interactions (as described per stud y protocol) for an y concomitant medication administered for treatment of SARS -CoV2 infection. 5.4.5. Dose Reductions Following dose interruption or cy cle delay due to toxicity , the investigational product(s) may need to be reduced when treatment is resumed. No specific dose adjustments are recommended for Grade 1/2treatment -related toxicity , unless otherwise specified. However, investigators should alway s manage their participants according to their medical judgment based on the particular clinical circumstances. PF-06936308 C3621001 Final Protocol Amendment 2, 22 Dec 2020 PFIZER CONFIDENTIAL Page 825.4.5.1. AdC68 Dose Reductions Changes in the dose levels for AdC68 will be discussed with the sponsor. Dose reduction of adenovirus b y 1dose level may be allowed in Part 1 depending on the t ype and severit y of toxicity encountered. No dose level reduction is allowed in Part 2. All dose modifications/adjustments must be clearl y documented in the participant’s source notes and CRF. Once a dose has been reduced for a given participant, all subsequent cy cles should be administered at that dose level for that participant, unless further dose reduction is required. Dose re -escalation for adenovirus is not allowed. Table 4. AdC68 Available Dose Levels (Part 1) Dose Level AdC68* +1 6 x 1011VP Starting 2 x 1011VP Table 5.AdC68 Available Dose Levels (Part 2) Dose Level AdC68* Starting 6 x 1011VP -1 2 x 1011VP Table 6. Dose Modifications for AdC68 Related Toxicity Toxicity Grade ½ Grade 3 Grade 4 Non-hematologic (other than irAE management described in Appendix 5)Continue at the same dose level.Withhold dose until toxicity is Grade 1, or has returned to baseline, then resume treatment at the same dose level or reduce the dose by 1level at the discretion of the investigator*.Discontinue treatment. Hem atologic Continue at the same dose level.Withhold dose until toxicity is Grade 2, or has returned to baseline, then resume treatment at the same dose level.Discontinue treatment. * Nausea, vomiting, or diarrhea must persist at Grade 3despite maximal medical therapy to require dose modification. 5.4.5.2. Tremelimumab Dose Reductions Changes in the dose levels for tremelimumab will be discussed with the sponsor. A dose reduction of tremelimumab by 1dose level (from 80 mg to 40 mg) may be allowed depending on the t ype and severit y of toxicity encountered. In addition, an intermediate dose may be considered. Participants requiring a dose level lower than 40 mg will be d iscontinued from treatment and enter into the follow- up phase unless otherwise agreed between the investigator and sponsor. Algorithms for the management of suspected pulmonary , PF-06936308 C3621001 Final Protocol Amendment 2, 22 Dec 2020 PFIZER CONFIDENTIAL Page 83gastrointestinal (GI), liver, endocrine, skin, neurological and renal toxicit ies have been developed (See Appendix 5). All dose modifications/adjustments must be clearl y documented in the participant’s source notes and case report form (CRF). Once a dose has been reduced for a given participant, all subsequent cy cles should be administered at that dose level, unless further dose reduction is required. Dose re -escalation for tremelimumab is not allowed. Table 7. Tremelimumab Available Dose Levels (Part 1) Dose Level Tremelimumab Starting 40 mg +1 80 mg Table 8.Tremelimumab Available Dose Levels (Part 2) Dose Level Tremelimumab Starting 80 mg -1 40 mg Table 9. Dose Modifications for Tremelimumab Related Toxicity When Given in Combination with AdC68 and pDNA Toxicity Grade ½ Grade 3 Grade 4 Non-hematologic Continue at the same dose level.Withhold dose until toxicity is Grade 1, or has returned to baseline, then resume treatment at the same dose level or reduce the dose by 1 level at the discretion of the investigator.*Discontinue treatment. Hem atologic Continue at the same dose level.Withhold dose until toxicity is Grade 2, or has returned to baseline, then resume treatment at the same dose level.Discontinue treatment. * Nausea, vomiting, or diarrhea must persist at Grade 3despite maximal medical therapy to require dose modification. 5.4.5.3. Sasanlimab Dose Reductions Events including, but not limited to, pneumonitis, colitis, creatinine and liver function test (LFT) elevation should be monitored carefull y with this class of agents. Dose reductions may be required for sasanlimab , tremelimumab or potentially both compou nds depending on the event and the severit y of the toxicity . Dose reductions of sasanlimab from 300 mg to 130 mg may be allowed. In addition an intermediate dose may be considered. All dose modifications/adjustments must be clearl y documented in the par ticipant’s source notes and CRF. PF-06936308 C3621001 Final Protocol Amendment 2, 22 Dec 2020 PFIZER CONFIDENTIAL Page 84Table 10. Sasanlimab Available Dose Levels (Part 1) Dose Level Sasanlimab Starting 130 mg +1 300 mg Table 11. Sasanlimab Available Dose Levels (Part 2) Dose Level Sasanlimab Starting 300 mg -1 130 mg Algorithms for the management of suspected pulmonary , GI, liver, endocrine, skin, neurological and renal toxicities have been developed (See Appendix 5). Participants requiring >4 weeks of dose interruption should be considered for discontinuation of treatment with sasanlimab . Participants may be allowed to resume dosing with the AdC68, pDNA and tremelimumab without sasanlimab for one dose with plans to resume sasanlimab at the next dosing time point if agreed upon by the investigator and sponsor. Participants who disconti nue sasanlimab due to toxicity will be allowed to remain in the study and continue treatment with the other components. The following serves as demonstrating general rules. Action may differ in specific cases based on evaluation by the investigator and th e sponsor. PF-06936308 C3621001 Final Protocol Amendment 2, 22 Dec 2020 PFIZER CONFIDENTIAL Page 85Table 12. Dose Modifications for Sasanlimab and/or Tremelimumab Related Toxicity Toxicity Grade 1 Grade 2 Grade 3 Grade 4 Non-hematologic Continue at the same dose level.For pneumonitis, endocrinopathy, colitis, creatinine, AST, ALT, or total bilirubin elevations, withhold dose until toxicity is Grade ≤1, or has returned to baseline, then resume at the same dose level or reduce by 1 level (considering each compound separately) at the discretion of the investigator . For all other events, continue at the same dose level.For pneumonitis, colitis, endocrinopathy, creatinine, AST, ALT or total bilirubin elevations, or pruritus discontinue treatment.** For all other events withhold dose until toxicity is Grade 1, or has returned to baseline, then resume treatment at the same dose level or reduce the dose by 1level (considering each compound separately) at the discretion of the investigator.* Treatment may resume with VBIR -2 with an interruption of sasanlimab for on e dose at the discretion of the investigator. Discontinue treatment.** Hem atologic Continue at the same dose level.Continue at the same dose level.Withhold dose until toxicity is Grade 2, or has returned to baseline, then resume treatment at the same dose level.Discontinue treatment.** * Nausea, vomiting, or diarrhea must persist at Grade 3despite maximal medical therapy to require dose modification. ** For Grade ≥3 colitis or pneumonitis, discontinue treatment permanently. For any grade of myocard itis discontinue treatment permanently. For all other conditions participants may be allow ed to remain in the study to receive the VBIR -2 2 after the toxicity is Grade ≤1 or returned to baseline, and only if agreed upon by the Investigator and Sponsor. 5.5.Investigational Product Storage The investigator, or an approved representative, eg, pharmacist will ensure that all investigational products are stored in a secured area with controlled access under required storage conditions and in accordance with applicable regulatory requirements. Investigational products should be stored in their original containers and in accordance with the labels. Upon receipt at the site, all drug product should be immediately transferred, in its original container, to the appro priate monitored storage area. Current storage conditions for PF-06936308 C3621001 Final Protocol Amendment 2, 22 Dec 2020 PFIZER CONFIDENTIAL Page 86AdC68 vials are frozen ( -20C 5C). The current storage conditions for the pDNA, tremelimumab and sasanlimab are refrigerated (2 -8C ). Any storage conditions stated in the SRSD will be supers eded b y the storage conditions stated on the product label. Please see the Instructions for Use for details on storage of the TDS -IM device. Site sy stems must be capable of measuring and documenting (for example, via a log), at a minimum, daily minimum an d maximum temperatures for all site storage locations (as applicable, including frozen, refrigerated, and/or room -temperature products). This should be captured from the time of investigational product receipt throughout the study . Even for continuous monitoring systems, a log or site procedure that ensures active evaluation for excursions should be available. The intent is to ensure that the minimum and maximum temperature is checked each business day to confirm that no excursion occurred since the last evaluation and to provide the site with the capability to store or view the minimum/maximum temperature for all nonworking day s upon return to normal operations. The operation of the temperature monitoring device and storage unit (for example, refrigerat or), as applicable, should be regularl y inspected to ensure they are maintained in working order. Any excursions from the product label storage conditions should be reported to Pfizer upon discovery . The site should actively pursue options for returning the product to the storage conditions described in the labeling, as soon as possible. Deviations from the storage requirements, including any actions taken, must be documented and reported to Pfizer. Once an excursion is identified, the investigational p roduct must be quarantined and not used until Pfizer provides permission to use the investigational product. It will not be considered a protocol deviation if Pfizer approves the use of the investigational product after the temperature excursion. Use of the investigational product prior to Pfizer approval will be considered a protocol deviation. Specific details regarding information the site should report for each excursion will be provided to the site. 5.6.Investigational Product Accountability The investigator site must maintain adequate records documenting the receipt, use, loss, or other disposition of the investigational product supplies. All investigational products will be accounted for using a drug accountabilit y form/record. 5.6.1. Destruction of Investigational Product Supplies The sponsor or designee will provide guidance on the destruction of unused investigational product (eg, at the site). If destruction is authorized to take place at the investigator site, the investigator must ensure t hat the materials are destroy ed in compliance with applicable environmental regulations, institutional policy , and any special instructions provided by Pfizer, and all destruction must be adequatel y documented. PF-06936308 C3621001 Final Protocol Amendment 2, 22 Dec 2020 PFIZER CONFIDENTIAL Page 875.7. Concomitant Treatment(s) Concomitant treatmen t considered necessary for the participant’s well- being may be given at discretion of the treating phy sician. All concomitant treatments, blood products, as well as nondrug interventions received b y participants from screening until the end of stud y visit will be recorded on the CRF. 5.7.1. Prohibited Concomitant Vaccines No vaccines (licensed or investigational) other than study vaccine, influenza, COVID- 19 and pneumococcal vaccines should be given during the study within 30 days prior to or after dosing . Other vaccines may be administered only if medically necessary (eg, tetanus post exposure prophy laxis). For participants who receive tremelimumab, live attenuated vaccines should not be administered within 30 day s prior to or after dosing with tremelimumab. Th e administration of inactivated vaccines are allowed. 5.7.2. Other Anti -tumor/Anti -Cancer or Experimental Drugs No additional anti -tumor treatment will be permitted while participants are receiving stud y treatment. Additionally, the concurrent use of select vitamins or herbal supplements is not permitted 5.7.3. Supportive Care Palliative and supportive care for disease related symptoms may be administered at the investigator’s discretion and according to an y available American Society of Clinical Oncology (ASCO) guidelines. Participants currently being treated with denosumab or bisphosphonates (eg, zoledronate) for bone disease may continue treatment while participating in this study . However, initiation of treatment with these t ypes of compounds should be avoided while participating in the study . Palliative radiotherap y on study is permitted for the treatment of painful bony lesions providing the lesions were known at the time of study entry and the investigator clearl y indicates that the need for palliative radio therapy is not indicative of disease progression. Participants currently being treated with a gonadotropin -releasing hormone agonist (GnRH agonist) may continue treatment while on clinical study C3621001 as long as the GnRH agonist treatment has been well tolerated for at least 3 months prior to study entry. 5.7.4. Hematopoietic Growth Factors Primary prophy lactic use of granulocy te-colony stimulating factors is not permitted during Cycle 1, but they may be used to treat treatment emergent neutropenia as indicated by the current American Society of Clinical Oncology guidelines.2 PF-06936308 C3621001 Final Protocol Amendment 2, 22 Dec 2020 PFIZER CONFIDENTIAL Page 88Erythropoietin may be used at the investigator’s discretion for the supportive treatment of anemia. 5.7.5. Anti -Diarrheal, Anti -Emetic Therapy Primary prophy laxis of diarrhea, nausea and vomiting is not permitted prior to the first dose of AdC68, tremelimumab and/or sasanlimab . Primary prophy laxis on subsequent dosing days is at the investigator’s discretion. The choice of the prophy lactic drug is up to the investigator with sponsor approval and assuming the drug is not prohibited as specified in Section 5.7 , as well as the duration of treatment assuming there is no known or expected drug-drug interaction. If so, then it must be approved by the sponsor. 5.7.6. Anti -Inflammatory Therapy Anti- inflammatory or narcotic analgesic may be offered as needed assuming there is no known or expected drug- drug interaction and assuming the drug is not included in the Concomitant Treatment(s) Section 5.7. 5.7.7. Corticosteroids Chronic, sy stemic corticosteroid use for palliative or supportive purpose is not permitted. The short term use of corticosteroids (e g, 5mg q.d. of prednisone for 2 weeks) as symptomatic treatment on an individual basis and upon discussion with the sponsor is allowed. Acute emergency administration, topical applications, inhaled spray s, eye drops, or local injections of corticosteroid s are allowed. 5.7.8. Surgery Caution is advised on theoretical grounds for an y surgical procedures during the stud y. The appropriat e interval of time between surgery and administration of VBIR -2 required to minimize the risk of impaired wound healing and blee ding has not been determined. Stopping all components of VBI R -2 is recommended at least 7 days prior to surgery . Postoperatively , the decision to reinitiate treatment should be based on a clinical assessment of satisfactory wound healing and recovery from surgery . 6. STUDY PROCEDURES 6.1.Screening For screening procedures see the Schedule of Activities and ASSESSMENTS sections. 6.2.Study Period For the treatment period procedures, see the Schedule of Activities and ASSESSMENTS sections. 6.3.End of Treatment The End of treatment visit will be completed at the time point when a decision is made to discontinue study treatment. This can occur during C ycles 1 or 2 or during the Maintenance PF-06936308 C3621001 Final Protocol Amendment 2, 22 Dec 2020 PFIZER CONFIDENTIAL Page 89Treatment Phase of the study . Obtain the specified EOT assessments (see Schedule of Activities ) if not completed in the past two weeks (past 6 weeks for tumor assessments). 6.4.Follow -up For follow -up procedures see the Schedule of Activities and ASSESSMENTS sections. 6.5.Survival Follow -up After treatment discontinuation, participant survival status will be collected every 3 month s until death, participant refusal, or lost to follow- up (telephone contact acceptable). 6.6. Participant Withdrawal Withdrawal of consent: Participants who request to discontinue receipt of study treatment will remain in the study and must continue to be followed for protocol specified follow-up procedures. The onl y exception to this is when a participant specificall y withdraws consent for any further contact with them or persons previously authorized by the participant to provide this information. Parti cipants should notify the investigator in writing of the decision to withdraw consent from future follow -up, whenever possible. The withdrawal of consent should be explained in detail in the medical records by the Investigator, as to whether the withdrawa l is only from further receipt of investigational product, or also from study procedures and/or posttreatment study follow -up; this information should be entered on the appropriate CRF page. In the event that survival status (whether the participant is alive or dead) is being measured, and if publicly available information is part of the origin of this data, it is important that collecting this information should be carried out onl y as appropriately directed in accordance with local law. Lost to follow- up: All reasonable efforts must be made to locate participants to determine and report their ongoing status. This includes follow -up with persons authorized by the participant as noted above. “Lost to Follow -up” is defined b y the inability to reach the par ticipant after a minimum of 2 documented phone calls, faxes, or e -mails as well as lack of response b y the participant to 1 letter sent by registered mail. All attempts should be documented in the participant’s medical records. If it is determined that the participant has died, the site will use locally -permissible methods to obtain the cause and the date of death. If the investigator’s use of a third- party representative to assist in the follow- up portion of the study has been included in the participan t’s informed consent, then the Investigator may use a sponsor -retained third- party representative to assist site staff with obtaining the participant’s contact information or other public survival status data necessary to complete the follow - up portion of the study . The site staff and representative will consult publicly available sources, such as public health registries and databases, in order to obtain updated contact information. If, after all attempts, the participant remains lost to follow- up, then the last -known- alive date PF-06936308 C3621001 Final Protocol Amendment 2, 22 Dec 2020 PFIZER CONFIDENTIAL Page 90as determined b y the Investigator should be reported and documented in the participant’s medical records. Participants may withdraw from treatment at any time at their own request, or they may be withdrawn at an y time at the discretion of the investigator or sponsor for safety (see also the Withdrawal From the Study Due to Adverse Events (see also the Participant Withdrawal Section) or behavioral reasons, or the inability of the participant to compl y with the protocol -required schedule of study visits or pro cedures at a given investigator site. Reasons for withdrawal of study treatment may include: Objective disease progression; Global deterioration of health status requiring discontinuation; Unacceptable toxicity ; Pregnancy ; Significant protocol violation; Lost to follow -up; Participant refused further treatment; Study terminated by sponsor; Death. Reasons for withdrawal from study follow -up may include: Completed study follow -up; Study terminated by sponsor; Lost to follow -up; Refused further follow -up; Death. If a participant does not return for a scheduled visit, every effort should be made to contact the participant. All attempts to contact the participant and information received during contact attempts should be documented in the participant’s medical record. Regardless of the circumstance, every effort should be made to document participant outcome, if possible. The Investigator should inquire about the reason for withdrawal, request that the participant PF-06936308 C3621001 Final Protocol Amendment 2, 22 Dec 2020 PFIZER CONFIDENTIAL Page 91return for a final visit, if applicable, and follow -up with the participant regarding any unresolved AEs. If the participant refuses further visits, the participant should continue to be followed for survival (if survival is a secondary endpoint) unless the participant withdraws consent for disclosur e of future information or for further contact. In this case, no further study -specific evaluations should be performed and no additional data should be collected. The Sponsor may retain and continue to use any data collected before such withdrawal of co nsent. 7.ASSESSMENTS Every effort should be made to ensure that the protocol -required tests and procedures are completed as described. However, it is anticipated that occasionall y there may be circumstances outside of the control of the investigator that ma y make it unfeasible to perform the test. In these cases the investigator must take all steps necessary to ensure the safet y and well -being of the participant. When a protocol- required test cannot be performed, the investigator will document the reason f or this and any corrective and preventive actions that he or she has taken to ensure that normal processes are adhered to as soon as possible. The study team will be informed of these incidents in a timely manner. For samples being collected and shipped, detailed collection, processing, storage, shipment instructions and contact information will be provided to the investigator site prior to initiation of the study . 7.1.Safety Assessment Safety assessments will include collection of AEs, serious adverse events (SAEs), vital signs and phy sical examination, electrocardiogram (ECG [12- lead]), laboratory assessments, including pregnancy tests and verification of concomitant treatments. 7.1.1. Pregnancy Testing All pregnancy tests used in this study , either urine or serum, must have a sensitivity of at least 25 mIU/mL and must be performed by a certified laboratory . For female participants of childbearing potential, 2 negative pregnancy tests are required before receiving study treatment(s) (1 negative pregnancy test at sc reening and 1 at the baseline visit immediately before stud y treatment administration). Following a negative pregnancy test result at screening, appropriate contraception must be commenced and the second negative pregnancy test result will then be require d at the baseline visit and within 5 day s after the first day of the menstrual period (counting the first day of the menstrual period as Day 1) before the participant may receive the study treatment. In the absence of regular menstrual bleeding, the study candidate should have used 2 forms of contraception for at least 1 month before the second pregnancy test. Pregnancy tests will also be routinely repeated at (pre -dose) every cycle (Day s 1, 29, 57, and 85) during the active treatment period, at the end o f study treatment, at the 28 -day Follow -Up visit to confirm that the participant has not become pregnant during the study . Pregnancy tests will also be done whenever 1 menstrual cy cle is missed or when potential pregnancy is otherwise suspected, and may be repeated if requested PF-06936308 C3621001 Final Protocol Amendment 2, 22 Dec 2020 PFIZER CONFIDENTIAL Page 92by institutional review boards (IRBs)/ethics committees (ECs) or if required by local regulations. In the case of a positive confirmed pregnancy , the participant will be withdrawn from administration of investigational product, but may remain in the study . For female participants who achieved postmenopausal status and have not experienced their menses since at least 12 consecutive month, a serum FSH test must be conducted at screening only, in order to confirm a FSH level within the laboratory ’s reference ranges for post menopause. 7.1.2.