A Dose Escalation and Expansion Study of RO7121661, a PD-1/TIM-3 Bispecific Antibody, in Participants With Advanced and/or Metastatic Solid Tumors

Inclusion Criteria:

General Inclusion Criteria:

- Life expectancy of ≥12 weeks

- Eastern Cooperative Oncology Group Performance Status 0-1

- Adequate cardiovascular function

- All acute toxic effects of any prior radiotherapy, chemotherapy, or surgical procedure
must have resolved to Grade ≤1, except alopecia (any grade) and Grade 2 peripheral
neuropathy

- Adequate hematological, liver, renal function

- Additional adequate laboratory parameters obtained within 14 days prior to the first
study treatment (Cycle [C] 1, Day [D] 1)

- Participants on therapeutic anticoagulation should be on a stable anticoagulant
regimen

- Negative HIV and hepatitis B surface antigen (HBsAg) test test at screening

- Negative total hepatitis B core antibody (HBcAb) test at screening, or positive total
HBcAb test followed by a negative hepatitis B virus (HBV) DNA test at screening

- Negative hepatitis C virus (HCV) antibody test at screening, or positive HCV antibody
test followed by a negative HCV RNA test at screening

- Diagnosis of locally advanced and/or metastatic solid tumors with radiologically
measurable disease according to RECIST v1.1

- Female participants: Woman of childbearing potential: Agree to remain abstinent or use
contraceptive methods that result in a failure rate of <1% per year during the
treatment period and for at least 4 months after the last dose of RO7121661. Have a
negative pregnancy test (blood) within the 7 days prior to the first study RO7121661
administration

- Male participants: During the treatment period and for at least 4 months after the
last dose of RO7121661, agreement to remain abstinent or use contraceptive measures
such as a condom plus an additional contraceptive method that together result in a
failure rate of <1% per year, with partners who are women of childbearing potential
Refrain from donating sperm for 4 months

Specific Inclusion Criteria for Biopsies:

- Participants who are enrolled on the parts of the study where fresh biopsies are
requested must have at least one tumor lesion accessible to biopsy per clinical judgment of
the treating physician and consent to undergo mandatory fresh baseline and on-treatment
biopsy. Bone lesion biopsies, bronchoscopy/trans-bronchial biopsies, and cytology fine
needle aspirates are not acceptable

Specific Inclusion Criteria for Part B Expansion in Checkpoint Inhibitor (CPI) Experienced
Patients:

- CPI experienced patients are defined as those who have had prior treatment with an
anti-PD-1 or anti-PD-L1 (programmed death-ligand 1) agent. Participants must meet the
following additional criteria to be eligible for inclusion in Part B of the study if
they are CPI experienced

- Participants with advanced and/or metastatic malignancies treated with anti-PD-L1/
anti-PD-1 with or without anti-CTLA-4 (cytotoxic T-lymphocyte-associated protein 4)
checkpoint inhibitor therapy

- The non-small cell lung cancer (NSCLC) and melanoma patients must have experienced
initial clinical benefit from CPI therapy for at least 4 months in which there was at
least one interval scan prior to 4 months demonstrating no progression of disease

- Participants who are considered to be deriving benefit from treatment post
progression, as per clinical judgment, are not considered eligible. Screening tumor
assessment should confirm progression

- Prior anti-PD-L1/PD-1 with or without anti-CTLA-4 as monotherapy and/or as combination
therapy may have been administered at any time during a participant's treatment
course, with the exception of adjuvant therapy

- Participants must have at least one tumor lesion accessible and adequate for biopsy
per clinical judgment of the treating physician and consent to undergo mandatory fresh
baseline and an additional on−treatment biopsy. Bone lesion biopsies,
bronchoscopy/trans-bronchial biopsies, and cytology fine needle aspirates are not

Specific Inclusion Criteria for Dose Expansion Cohort B3 in Untreated Cancer Immunotherapy
(CIT)-Naïve NSCLC Cohort:

- Participants must have at least one tumor lesion accessible to biopsy per clinical
judgment of the treating physician and consent to undergo mandatory fresh baseline and
on-treatment biopsy. Bone lesion biopsies, bronchoscopy/trans-bronchial biopsies, and
cytology fine needle aspirates are not acceptable

- Participants with histologically confirmed advanced NSCLC with PD-L1 high TPS ≥50%,
used interchangeably with tumor cell staining, assessed locally, using 22C3 clone

- Not previously treated with cancer immunotherapeutic agents, including anti-PD-L1/PD-1
and/or anti-CTLA-4

Exclusion Criteria:

General Exclusion Criteria:

- Known hypersensitivity to any of the components of RO7121661

- History or clinical evidence of central nervous system primary tumors or metastases
including leptomeningeal metastases, unless they have been previously treated, are
asymptomatic, and have had no requirement for steroids or enzyme-inducing
anticonvulsants in the last 14 days prior to Screening

- Participants with an active second malignancy

- Evidence of significant, uncontrolled concomitant diseases that could affect
compliance with the protocol or interpretation of results, including diabetes
mellitus, history of relevant pulmonary disorders, and known autoimmune diseases or
immune deficiency, or other disease with ongoing fibrosis

- Encephalitis, meningitis, or uncontrolled seizures in the year prior to informed
consent

- Severe dyspnea or requiring supplemental oxygen therapy at rest

- Significant cardiovascular/cerebrovascular vascular disease within 6 months prior to
D1 of study drug administration and history of thromboembolic events within 6 months
of enrollment

- Known active or uncontrolled bacterial, viral, fungal, mycobacterial, parasitic, or
other infection or any major episode of infection requiring treatment with IV
antibiotics or hospitalization within 4 weeks prior to the start of drug
administration

- Vaccination with live vaccines within 28 days prior to the start of treatment

- Known clinically significant liver disease

- Major surgical procedure or significant traumatic injury within 28 days prior to C1D1,
or anticipation of the need for major surgery during the course of the study

- Any other diseases, metabolic dysfunction, physical examination finding, or clinical
laboratory finding giving reasonable suspicion of a disease or condition that
contraindicates the use of an investigational drug or that may affect the
interpretation of the results or render the participant at high risk from treatment
complications

- Dementia or altered mental status that would prohibit informed consent

- Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent
drainage procedures

- Adverse events from any prior anti-cancer therapy that have not resolved to Grade ≤1
except for alopecia, vitiligo, or endocrinopathy managed with replacement therapy

- Active or history of autoimmune disease or immune deficiency

- For Part A and Part B1 (CPI experienced melanoma patients): prior treatment with CPIs,
immunomodulatory monoclonal antibodies (mAbs), and/or mAb-derived therapies is allowed
provided that at least 6 weeks have elapsed between the last dose and the proposed
C1D1

- For Part B2 (PD-1/PD-L1 and chemotherapy experienced NSCLC patients): prior treatment
with immunomodulatory agents for cancer therapy, other than anti-PD-1 or anti-PD-L1
agents and TIM-3 inhibitor or lymphocyte-activation gene 3 (LAG-3) inhibitor is
prohibited

- Prior treatment with a TIM-3 inhibitor or LAG-3 inhibitor is prohibited

- Concurrent therapy with any other investigational drug <28 days or 5 half-lives of the
drug, whichever is shorter, prior to the first RO7121661 administration on C1D1

- Immuno-modulating agents: Last dose with any of the following agents, for example,
etanercept, infliximab, tacrolimus, cyclosporine, mycophenolic acid, alefacept, or
efalizumab <28 days prior to C1D1 and regular immunosuppressive therapy

- Chronic use of steroids (excluding topical and inhaled) and concurrent high doses of
systemic corticosteroids will not be allowed. High dose is considered as >20 mg of
dexamethasone a day for >7 consecutive days.

- Radiotherapy within the last 4 weeks before start of study drug treatment, with the
exception of limited palliative radiotherapy

- Eligibility of participants who require blood transfusion before and after the start
of the study treatment should be discussed by the Sponsor and Investigator

Specific Exclusion Criteria for Part B1 and Part B2 Expansion Cohorts (CPI experienced
patients):

- Any history of an immune-mediated adverse event (including Grade 4) attributed to
prior CIT that resulted in permanent discontinuation of the prior immunotherapeutic
agent and/or occurred ≤6 months prior to planned C1D1

- All immune-mediated adverse events related to prior immunomodulatory therapy must have
resolved completely to baseline. Participants treated with corticosteroids for
immune-mediated adverse events must demonstrate absence of related symptoms or signs
for ≥4 weeks following discontinuation of corticosteroids

Specific Exclusion Criteria for Part B3 Expansion Cohort:

- Prior therapy for metastatic disease is not permitted

- Adjuvant anti-PD-1 or anti-PD-L1 therapy is not allowed. Adjuvant chemotherapy is
permitted as long as treatment was administered >6 months prior