A Safety Study of Talimogene Laherparepvec Combined With Atezolizumab for Triple Negative Breast Cancer and Colorectal Cancer With Liver Metastases

The Screening period is 28 days prior to study enrollment. This study has 2 Cohorts. Cohort
1: Triple Negative Breast Cancer and Cohort 2: Colorectal Cancer. These cohorts will enroll
in parallel. There will be a Safety Follow-up period and a Long Term Follow-up period.

Drug Administration: The participants will receive the study drugs in cycles. If the
participants are found to be eligible to take part in this study, they will receive
talimogene laherparepvec as an injection into the hepatic (liver) metastatic sites on Day 1
of each cycle along with receiving atezolizumab by intravenous infusion on Day 1 of each
cycle. Each cycle is 21 days for 6 cycles. There is an option for an additional 6 cycles
after the first 6 intra-hepatic cycles. After the first radiographic assessment at week 10,
if all injectable liver lesions have been injected but the 4.0 mL maximum volume has not been
used, injection of clinically assessed non-hepatic cutaneous, subcutaneous, and nodal tumor
lesions with or without ultrasound guidance will be permitted. Liver lesions should be
prioritized over cutaneous, subcutaneous and nodal lesions.

Treatment will continue until a participant experiences a DLT (Dose Limiting Toxicity)
evaluated in the DLT period (which is 2 cycles from initial dose), has CR (Complete
Response), has need for an alternative anticancer therapy or experiences a safety concern.

Study Visits: Cycle 1 to Cycle 12 - The participant will have a physical exam along with
vital signs and ECOG (Eastern Cooperative Oncology Group) performance level assessment. Blood
(about 2 Tablespoons) will be drawn for routine tests and to check the immune system. Adverse
events and medications taken will be reviewed on each cycle.Biomarkers will be taken on
cycles 1, 2, 3, 6, and safety FU. Tumor Markers (special lab tests associated with the
cancer, such as particular proteins) will be completed will be take on cycles 1, 4, 7, 10,
13, every 3 cycles and SFU.

Central lab tests will be completed on cycles 1, 2, 3, and 6 and safety FU. Cycle 1 Archived
(prior stored) tumor sample will be obtained. Also, a liver tumor biopsy will be completed at
Cycles 1, 3 and 6.

Response Assessments will be completed at Screening and again at Cycles 4, 7, 10, 13 and
every 3 cycles.

Throughout the trial a swab for Herpetic tumor will be obtained within 3 days of the event.

Cycle 1 to 12- The exposure to talimogene laherparepvec by the subject's healthcare provider
and household member caregiver will be reviewed. Cycles 1, 3, 6-Liver tumor biopsy will be
completed. Cycles 4, 7, 10, 13 and every 3 cycles -Response assessments will be completed by
radiographic and clinical tumor assessment.

Length of Treatment:

A maximum for 12 cycles of talimogene laherparepvec are allowed during the study. The
participant may continue taking the study drug for as long as the doctor thinks it is in
their best interest. The participant will no longer be able to take the study drug if the
disease gets worse, or if they are unable to follow study directions.

Safety Follow-up Visit:

Safety Follow-up visit will be performed about 30 days after the last dose of study
treatment.

The participant will have a physical exam, have vital signs taken, assessment of ECOG status
and have weight measured. Adverse events will be assessed as well as the concominant
medications. Routine bloodwork and tumor markers will be taken.

Exposure to talimogene laherparepvec by the healthcare providers of the participant and/or
close contacts will be assessed.

Long-Term Follow-up Visits: Participants will be followed for survival every 12 weeks from
the date of the safety follow-up visit until approximately 24 months after the last subject
is enrolled. Subsequent cancer treatments will be collected as part of the long-term
follow-up survival assessment. This is an investigational study. The study doctor can explain
how the study drugs are designed to work.

Inclusion Criteria:

- Criteria1, Participant provided informed consent prior to any study-specific
activities/procedures -Criteria 2, Confirmation of triple negative breast cancer or
colorectal cancer with liver metastases by laboratory testing

- Criteria 3, Participants had disease progression during or after one or more prior
standard of care systemic anti-cancer therapy (eg chemotherapy, targeted therapy) for
metastatic disease

- Criteria 4, Participants have measurable disease which is equal to one or more
metastatic liver lesions that can be accurately and serially measured that are greater
than or equal to 1 cm dimension and for which the longest diameter is greater or equal
to 1 cm as measured by CT (Computed Tomography) scan or magnetic resonance imaging.
The metastatic liver lesion(s) must not be in an area that received prior localized
therapies.

- Criteria 5, Metastatic liver lesions for injection must be without necrosis (dead
tissue )and must be be located where any tumor swelling will not lead to gall bladder
tract obstruction or lead to bleeding risk

- Criteria 6, Eastern Cooperative Oncology Group performance status (ECOG PS) 0 or 1

- Criteria 7, Life expectancy greater than or equal to 5 months

- Criteria 8, Adequate organ function within 4 wks prior to enrollment. This includes
hematology, renal, hepatic and blood-clotting functions as defined by protocol.

- Criteria 9, Female subjects of childbearing potential should have a negative serum
pregnancy test within 1 week prior to enrollment

- Criteria 10, Other Inclusion Criteria May Apply.

Exclusion criteria:

- Criteria 1, Participant is a candidate for hepatic surgery or local regional therapy
of liver metastases with curative intent

- Criteria 2, More than one third of the liver is estimated to be involved with
metastases

- Criteria 3, There is invasion by cancer into the main blood vessels such as the portal
vein, hepatic vein or the vena cava

- Criteria 4, Participant is currently receiving or has received liver
metastatic-directed therapy ( eg: radiation, ablation, embolization) less than 4 wks
prior to enrollment or hepatic surgery

- Criteria 5, History of other malignancy within the past 5 years prior to enrollment
with some exceptions, as outlined in the protocol.

- Criteria 6, Active or untreated central nervous system (CNS) metastases per CT or MRI
evaluation during screening

- Participants with a history of CNS metastases are eligible provided they are stable
and meet the criteria details in the protocol.

- Other Medical Conditions as noted in the protocol.

- Criteria 7, Other Exclusion Criteria May Apply