A Study of RO7172508 in Patients With Locally Advanced and/or Metastatic CEA-Positive Solid Tumors

• Sponsor: Hoffmann-La Roche (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT03539484
• Collaborator: (none)
• Enrollment: 26
• Locations: 6
• Arms: 3
• Actual Duration (Months): 12.6
• Patients Per Site: 4.3
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

This study was to determine the maximum-tolerated dose (MTD) and/or the optimal biological dose (OBD) as well as the optimal schedule for intravenous (IV) and subcutaneous (SC) administrations of RO7172508 as monotherapy, with or without obinutuzumab pre-treatment, in participants with locally advanced and/or metastatic carcinoembryonic antigen (CEA)-positive solid tumors who have progressed on standard of care (SOC) treatment, are intolerant to SOC, and/or are non-amenable to SOC. This study was conducted in two parts. Part I of the study consisted of an IV single participant cohort/multiple-ascending dose-escalation to evaluate the safety of RO7172508. Part II was a multiple participant cohort/multiple-ascending dose-escalation to define the MTD and/or OBD of RO7172508 administered as single agent, IV and/or SC, in participants with tumors that are expressing high as well as moderate/low-CEA. The study switched from Part I to Part II when the maximum planned dose for Part I was reached or the occurrence of a RO7172508-related Grade >= 2 adverse event (AE) or dose-limiting toxicity (DLT) was observed, whichever comes first. The Sponsor may decide to switch from Part I to Part II in the absence of an observed RO7172508-related Grade >= 2 toxicity or prior to maximum planned dose for Part I.

Condition or Disease	Intervention/Treatment	Phase
Solid Tumors	Drug: RO7172508; Drug: Obinutuzumab; Drug: Tocilizumab	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 26 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A First-in-Human, Open-Label, Multicenter, Dose-Escalation Phase I Clinical Study of Single-Agent RO7172508 in Patients With Locally Advanced and/or Metastatic CEA-Positive Solid Tumors
• Actual Study Start Date: Jul 4, 2018
• Actual Primary Completion Date: Jul 22, 2019
• Actual Study Completion Date: Jul 22, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Part I: Single Participant Cohorts IV/MAD-Escalation Part I was a multiple-ascending dose-escalation in single participant cohorts. RO7172508 was administered intravenously once every 3 weeks (Q3W). The starting dose of RO7172508 was 65 microgram (mcg) and the maximum dose explored was 1.6 milligram (mg).	Drug: RO7172508; RO7172508 was administered at a dose and as per the schedule specified in the respective arms.; Drug: Tocilizumab; Tocilizumab was administered if required, for the management of severe CRS (cytokine release syndrome)
Experimental: Part II: Multiple Participant Cohorts IV/MAD-Escalation Multiple ascending dose-escalation of IV-administered RO7172508 in multiple participant cohorts: The starting-dose for the initiation of the IV dose-escalation was determined by Part I and RO7172508 was initially given Q3W. Dose-escalation was undertaken based on safety until determination of the MTD or the highest safe dose if MTD is not reached. If on-target toxicity was reported in the first cycle of treatment, fractionated dosing may be implemented for the first cycle to improve tolerability.	Drug: RO7172508; RO7172508 was administered at a dose and as per the schedule specified in the respective arms.; Drug: Obinutuzumab; In the event obinutuzumab treatment is implemented, obinutuzumab will be administered either on Day-7 or on Day-7 and Day-6. If obinutuzumab is given only on one day, then the schedule for Day-7 should be followed including an end of infusion sample.; Drug: Tocilizumab; Tocilizumab was administered if required, for the management of severe CRS (cytokine release syndrome)
Experimental: Part II: Multiple Participant Cohorts SC/MAD-Escalation (QW) Multiple ascending dose-escalation of SC-administered RO7172508 in multiple participant cohorts. These will be initiated once the IV schedule has shown RO7172508 preliminary clinical activity or the MTD has been established and is equal to or above 2 mg. The starting-dose and regimen once a week or once every 3 weeks (QW or Q3W) for SC administration will be proposed based on the evaluation of the safety and PK data observed following IV administration but will not exceed the highest safe dose tested in the IV Q3W dose escalation; a minimum dose of 2 mg is defined for a single SC administration. In addition, the QW SC starting-dose will not exceed one third of the IV MTD or of the highest safe IV dose tested. Dose escalation will continue based on safety until determination of the MTD or the planned maximum dose of 400 mg. If on-target toxicity is reported in the first cycle of treatment, fractionated dosing may be implemented for the first cycle to improve tolerability.	Drug: RO7172508; RO7172508 was administered at a dose and as per the schedule specified in the respective arms.; Drug: Obinutuzumab; In the event obinutuzumab treatment is implemented, obinutuzumab will be administered either on Day-7 or on Day-7 and Day-6. If obinutuzumab is given only on one day, then the schedule for Day-7 should be followed including an end of infusion sample.; Drug: Tocilizumab; Tocilizumab was administered if required, for the management of severe CRS (cytokine release syndrome)

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Dose Limiting Toxicities (DLTs) [Up to approximately 12 months]

   Number of participants with DLTs.

2. Percentage of Participants With Adverse Events [60 days after last dose of study treatment (up to approximately 12 months)]

   Percentage of participants with adverse events.

Secondary Outcome Measures

1. Maximum Concentration of RO7172508 [Cycle 1 following single dose administration of RO7172508]

2. Time of Maximum Concentration of RO7172508 [Cycle 1 following single dose administration of RO7172508]

3. Clearance or Apparent Clearance of RO7172508 [Cycle 1 following single dose administration of RO7172508]

4. Volume of Distribution at Steady State of RO7172508 [Cycle 1 following single dose administration of RO7172508]

5. Area Under the Plasma Concentration Time-Curve From Zero to the Last Measured Concentration (AUClast) of RO7172508 [Cycle 1 following single dose administration of RO7172508]

6. Area Under the Serum Concentration Versus Time Curve Computed From Time of Dosing to Infinity (AUCinf) of RO7172508 [Cycle 1 following single dose administration of RO7172508]

7. Dose Normalized Area Under the Serum Concentration Versus Time Curve Computed From Time of Dosing to Infinity (AUCinf/Dose) of RO7172508 [Cycle 1 following single dose administration of RO7172508]

8. Half-Life of RO7172508 [Cycle 1 following single dose administration of RO7172508]

9. Presence or Absence and Titer of ADAs [Up to approximately 12 months]

10. Changes in Frequency of Tumor Infiltrating Lymphocytes [Cycle 1 Day 1 (Pre-treatment), Cycle 2 Day 8 (Cycle is 21 days)]

11. Secondary: Changes in Activation Status of Tumor Infiltrating Lymphocytes (% of CD8) [Cycle 1 Day 1 (Pre-treatment), Cycle 2 Day 8 (Cycle is 21 days)]

12. Changes in Activation Status of Tumor Infiltrating Lymphocytes (% of CD4) [Cycle 1 Day 1 (Pre-treatment), Cycle 2 Day 8 (Cycle is 21 days)]

13. Changes in Spatial Distribution of Tumor Infiltrating Lymphocytes [Cycle 1 Day 1 (Pre-treatment), Cycle 2 Day 8 (Cycle is 21 days)]

    Spatial distribution of TIL's analyzed by performing IHC assay, which measures the density and intra-tumoral location of CD8+ T cells and reports "CD8 T cell immune phenotypes". These are classified as "desert", "excluded" and "inflamed".

14. Objective Response Rate (ORR) [Up to approximately 12 months]

    Objective response was defined as a Complete Response (CR) or Parital Response (PR), as determined by the Investigator's assessment using RECIST v1.1 and confirmed by repeat assessments >= 4 weeks after initial documentation. To classify a response as SD, measurements are classified as stable (according to RECIST v1.1) at least once after study entry at a minimum of 6 weeks after study entry.

15. Disease Control Rate (DCR) [Up to approximately 12 months]

    DCR is determined as the rate of participants with an observed tumor response of CR or PR (ORR) or CR, PR or SD (DCR). DCR is to be derived for RECIST v1.1.

16. Duration of Response (DOR) [Up to approximately 12 month]

    Among participants with an objective response (responders), DOR will be defined as the time from first occurrence of a documented objective response until the time of documented disease progression or death within 30 days from last study treatment from any cause during treatment, whichever occurs first. This will be calculated for participants who have a best overall response of CR or PR as defined per RECIST v1.1 and per iRECIST.

17. Progression Free Survival (PFS) [Up to approxmately 12 months]

    PFS (on-treatment) will be defined as the time from study treatment initiation (Cycle 1 Day 1) to the first occurrence of documented disease progression or death from any cause during treatment (death within 30 days from last study treatment), whichever occurs first.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• For Part I: participants with locally advanced and/or metastatic solid tumor with confirmed cytoplasmic and/or membranous high CEA expression in tumor tissue is required. Participants must have progressed on a SOC therapy, be intolerant to SOC, and/or are non-amenable to SOC.

• For <12 mg dose cohorts, serum CEA levels below a certain threshold is required as follows:

• For dose cohorts 65-159 microgram, a sCEA level of < 22 ng/mL

• For dose cohorts 160-399 microgram, a sCEA level of < 28 ng/mL

• For dose cohorts 400-799 microgram, a sCEA level of < 44 ng/mL

• For dose cohorts 800-1599 microgram, a sCEA level of < 70 ng/mL

• For the dose cohort of 1.6-3.1 milligram, a sCEA level of < 123 ng/mL

• For the dose cohort of 3.2-6.3 milligram, an sCEA level of < 229 ng/mL.

• For the dose cohort of 6.4-11.9 milligram, an sCEA level of < 440 ng/mL. If dose fractionation is implemented, the sCEA threshold for inclusion should correspond to the dose range of the first dose administered.

• For Part II, participants with locally advanced and/or metastatic solid tumor expressing cytoplasmic and/or membranous high-CEA or moderate/low-CEA on archival material, who have progressed on a SOC therapy, are intolerant to SOC, and/or are non-amenable to SOC. Participants must have a lesion amenable to biopsy (except participants with NSCLC, which may be enrolled with archival tissue available only). For participants with colorectal cancer (CRC) only, the CEA assessment by immunohistochemistry should be performed but the result is not required to enroll the participant.

• Radiologically measurable disease according to RECIST v1.1.

• Life expectancy of >= 12 weeks

• Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0-1.

• All acute toxic effects of any prior radiotherapy, chemotherapy, or surgical procedure must have resolved to Grade <= 1 or returned to baseline except alopecia (any grade) and Grade 2 peripheral neuropathy.

• Adequate hematological, liver, renal, and lung function

• For women: agree to remain abstinent or use two contraceptive methods that result in a failure rate of <1% per year from screening until 2 months after the last dose of RO7172508 and have a negative pregnancy test within one week prior to the first study treatment administration

• For men: 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 woman of childbearing potential and refrain from donating sperm during the study

Exclusion Criteria:

• History or clinical evidence of central nervous system (CNS) primary tumors or 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 before screening.

• Non-irradiated lesions > 2 cm at critical sites where tumor swelling induced by RO7172508 is expected to lead to significant complications.

• Another invasive malignancy in the last 2 years

• Evidence of significant, uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of results or contraindicate the use of an investigational drug.

• Uncontrolled hypertension, unstable angina, congestive heart failure, serious cardiac arrhythmia that requires treatment with the exceptions of atrial fibrillation and paroxysmal supraventricular tachycardia, and history of myocardial infarction within 6 months of enrollment.

• Active or uncontrolled infections.

• Known hepatitis B or C

• Major surgery or significant traumatic injury < 28 days prior to the first RO7172508 administration or anticipation of the need for major surgery during study treatment.

Specific Exclusion Criteria if Pre-treatment with Obinutuzumab is Implemented:

• Known HIV

• Positive test results for HBV infection, HBcAb indicating an active viral infection and positive test results for HCV.

• Participants positive for HCV antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV ribonucleic acid (RNA).

• History of progressive multifocal leukoencephalopathy.

• Active TB requiring treatment within 3 years prior to baseline.

• Latent TB diagnosed during Screening.

• Positive test results for human T-lymphotropic virus 1

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Cliniques Universitaires St-Luc	Bruxelles		Belgium	1200
2	Princess Margaret Cancer Center	Toronto	Ontario	Canada	M5G 1Z5
3	Rigshospitalet; Onkologisk Klinik	København Ø		Denmark	2100
4	Clinica Universitaria de Navarra	Pamplona	Navarra	Spain	31008
5	Hospital Univ Vall d'Hebron; Servicio de Oncologia	Barcelona		Spain	08035
6	START Madrid. Centro Integral Oncologico Clara Campal; CIOCC	Madrid		Spain	28050

Sponsors and Collaborators

• Hoffmann-La Roche

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Dec 26, 2018

More Information

Publications

None provided.

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT03539484
• Other Study ID Numbers: BP40092
• First Posted: May 29, 2018
• Last Update Posted: Sep 3, 2020
• Last Verified: Aug 1, 2020

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Neoplasms; Obinutuzumab

Study Results

Participant Flow

Arm/Group Title	PART1 - RO7172508 - Q3W - 65 mcg	PART1 - RO7172508 - Q3W - 160 mcg	PART1 - RO7172508 - Q3W - 400 mcg	PART2 - RO7172508 - Q3W - 400 mcg	PART2 - RO7172508 - Q3W - 800 mcg	PART2 - RO7172508 - Q3W - 1200 mcg	PART2 - RO7172508 - Q3W - 1800 mcg
Arm/Group Description	Part I was a multiple-ascending dose-escalation in single participant cohorts. RO7172508 was administered intravenously once every 3 weeks (Q3W) at a dose of 65 microgram (mcg).	Part I was a multiple-ascending dose-escalation in single participant cohorts. RO7172508 was administered intravenously once every 3 weeks (Q3W) at a dose of 160 microgram (mcg).	Part I was a multiple-ascending dose-escalation in single participant cohorts. RO7172508 was administered intravenously once every 3 weeks (Q3W) at a dose of 400 microgram (mcg).	Part II was a multiple ascending dose-escalation of IV-administered RO7172508 in multiple participant cohorts: The starting-dose for the initiation of the IV dose-escalation was determined by Part I and RO7172508 was initially given Q3W. Starting dose of RO7172508 was 400 mcg.	Part II was a multiple ascending dose-escalation of IV-administered RO7172508 in multiple participant cohorts. RO7172508 was administered intravenously at a dose of 800 mcg.	Part II was a multiple ascending dose-escalation of IV-administered RO7172508 in multiple participant cohorts. RO7172508 was administered intravenously at a dose of 1200 mcg.	Part II was a multiple ascending dose-escalation of IV-administered RO7172508 in multiple participant cohorts. RO7172508 was administered intravenously at a dose of 1800 mcg.
Period Title: Overall Study
STARTED	1	1	1	3	13	5	2
COMPLETED	0	0	0	0	0	0	0
NOT COMPLETED	1	1	1	3	13	5	2

Baseline Characteristics

Arm/Group Title	PART1 - RO7172508 - Q3W - 65 mcg	PART1 - RO7172508 - Q3W - 160 mcg	PART1 - RO7172508 - Q3W - 400 mcg	PART2 - RO7172508 - Q3W - 400 mcg	PART2 - RO7172508 - Q3W - 800 mcg	PART2 - RO7172508 - Q3W - 1200 mcg	PART2 - RO7172508 - Q3W - 1800 mcg	Total
Arm/Group Description	Part I was a multiple-ascending dose-escalation in single participant cohorts. RO7172508 was administered intravenously once every 3 weeks (Q3W) at a dose of 65 microgram (mcg).	Part I was a multiple-ascending dose-escalation in single participant cohorts. RO7172508 was administered intravenously once every 3 weeks (Q3W) at a dose of 160 microgram (mcg).	Part I was a multiple-ascending dose-escalation in single participant cohorts. RO7172508 was administered intravenously once every 3 weeks (Q3W) at a dose of 400 microgram (mcg).	Part II was a multiple ascending dose-escalation of IV-administered RO7172508 in multiple participant cohorts: The starting-dose for the initiation of the IV dose-escalation was determined by Part I and RO7172508 was initially given Q3W. Starting dose of RO7172508 was 400 mcg.	Part II was a multiple ascending dose-escalation of IV-administered RO7172508 in multiple participant cohorts. RO7172508 was administered intravenously at a dose of 800 mcg.	Part II was a multiple ascending dose-escalation of IV-administered RO7172508 in multiple participant cohorts. RO7172508 was administered intravenously at a dose of 1200 mcg.	Part II was a multiple ascending dose-escalation of IV-administered RO7172508 in multiple participant cohorts. RO7172508 was administered intravenously at a dose of 1800 mcg.	Total of all reporting groups
Overall Participants	1	1	1	3	13	5	2	26
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	53.0 (NA)	60.0 (NA)	60.0 (NA)	53.7 (9.6)	62.2 (9.0)	58.8 (13.5)	55.5 (16.3)	59.5 (9.8)
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%	1 33.3%	7 53.8%	4 80%	2 100%	14 53.8%
Male	1 100%	1 100%	1 100%	2 66.7%	6 46.2%	1 20%	0 0%	12 46.2%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Not Hispanic or Latino	1 100%	1 100%	1 100%	3 100%	13 100%	5 100%	2 100%	26 100%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
White	1 100%	1 100%	1 100%	3 100%	13 100%	5 100%	2 100%	26 100%
More than one race	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Dose Limiting Toxicities (DLTs)
Description	Number of participants with DLTs.
Time Frame	Up to approximately 12 months

Outcome Measure Data

Analysis Population Description

DLT evaluble population included participants who completed the DLT window without a DLT, or participants who reported with a DLT.

Arm/Group Title	Part I: Single Participant Cohort IV RO7172508 65 mcg	Part I: Single Participant Cohort IV RO7172508 160 mcg	Part I: Single Participant Cohort IV RO7172508 400 mcg	Part II: Multiple Participant Cohorts IV 400 mcg	Part II: Multiple Participant Cohorts IV 800 mcg	Part II: Multiple Participant Cohorts IV 1200 mcg	Part II: Multiple Participant Cohorts IV 1800 mcg
Arm/Group Description	Part I was a multiple-ascending dose-escalation in single participant cohorts. RO7172508 was administered intravenously once every 3 weeks (Q3W) at a dose of 65 microgram (mcg).	Part I was a multiple-ascending dose-escalation in single participant cohorts. RO7172508 was administered intravenously once every 3 weeks (Q3W) at a dose of 160 microgram (mcg).	Part I was a multiple-ascending dose-escalation in single participant cohorts. RO7172508 was administered intravenously once every 3 weeks (Q3W) at a dose of 400 microgram (mcg).	Part II was a multiple ascending dose-escalation of IV-administered RO7172508 in multiple participant cohorts: The starting-dose for the initiation of the IV dose-escalation was determined by Part I and RO7172508 was initially given Q3W. Starting dose of RO7172508 was 400 mcg.	Part II was a multiple ascending dose-escalation of IV-administered RO7172508 in multiple participant cohorts. RO7172508 was administered intravenously at a dose of 800 mcg.	Part II was a multiple ascending dose-escalation of IV-administered RO7172508 in multiple participant cohorts. RO7172508 was administered intravenously at a dose of 1200 mcg.	Part II was a multiple ascending dose-escalation of IV-administered RO7172508 in multiple participant cohorts. RO7172508 was administered intravenously at a dose of 1800 mcg.
Measure Participants	0	0	1	3	13	5	2
Number [Participants]	0 0%	0 0%	1 100%	0 0%	1 7.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part I: Single Participant Cohort IV RO7172508 400 mcg, Part II: Multiple Participant Cohorts IV 400 mcg, Part II: Multiple Participant Cohorts IV 800 mcg, Part II: Multiple Participant Cohorts IV 1200 mcg, Part II: Multiple Participant Cohorts IV 1800 mcg
	Comments
	Type of Statistical Test	Other
	Comments	A Bayesian approach is used to estimate the maximum tolerated dose (MTD).
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Posterior probability at dose 1.8 mg
	Estimated Value	10.6
	Confidence Interval	(2-Sided) 95%; 2.10 to 26.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	Percentage of Participants With Adverse Events
Description	Percentage of participants with adverse events.
Time Frame	60 days after last dose of study treatment (up to approximately 12 months)

Outcome Measure Data

Analysis Population Description

Safety population included all participants enrolled in the study who received at least one dose of study treatment.

Arm/Group Title	Part I: Single Participant Cohort IV RO7172508 65 mcg	Part I: Single Participant Cohort IV RO7172508 160 mcg	Part I: Single Participant Cohort IV RO7172508 400 mcg	Part II: Multiple Participant Cohorts IV 400 mcg	Part II: Multiple Participant Cohorts IV 800 mcg	Part II: Multiple Participant Cohorts IV 1200 mcg	Part II: Multiple Participant Cohorts IV 1800 mcg
Arm/Group Description	Part I was a multiple-ascending dose-escalation in single participant cohorts. RO7172508 was administered intravenously once every 3 weeks (Q3W) at a dose of 65 microgram (mcg).	Part I was a multiple-ascending dose-escalation in single participant cohorts. RO7172508 was administered intravenously once every 3 weeks (Q3W) at a dose of 160 microgram (mcg).	Part I was a multiple-ascending dose-escalation in single participant cohorts. RO7172508 was administered intravenously once every 3 weeks (Q3W) at a dose of 400 microgram (mcg).	Part II was a multiple ascending dose-escalation of IV-administered RO7172508 in multiple participant cohorts: The starting-dose for the initiation of the IV dose-escalation was determined by Part I and RO7172508 was initially given Q3W. Starting dose of RO7172508 was 400 mcg.	Part II was a multiple ascending dose-escalation of IV-administered RO7172508 in multiple participant cohorts. RO7172508 was administered intravenously at a dose of 800 mcg.	Part II was a multiple ascending dose-escalation of IV-administered RO7172508 in multiple participant cohorts. RO7172508 was administered intravenously at a dose of 1200 mcg.	Part II was a multiple ascending dose-escalation of IV-administered RO7172508 in multiple participant cohorts. RO7172508 was administered intravenously at a dose of 1800 mcg.
Measure Participants	1	1	1	3	13	5	2
Number [Percentage of participants]	100 10000%	100 10000%	100 10000%	100 3333.3%	100 769.2%	100 2000%	100 5000%

3. Secondary Outcome

Title	Maximum Concentration of RO7172508
Time Frame	Cycle 1 following single dose administration of RO7172508

Outcome Measure Data

Analysis Population Description

Pharmacokinetic population included all participants who received at least one dose of study treatment and who had data from at least one post-dose sample.

Arm/Group Title	Part I: Single Participant Cohort IV RO7172508 65 mcg	Part I: Single Participant Cohort IV RO7172508 160 mcg	Part I and Part II: Participant Cohorts IV 400 mcg	Part II: Multiple Participant Cohorts IV 800 mcg	Part II: Multiple Participant Cohorts IV 1200 mcg	Part II: Multiple Participant Cohorts IV 1800 mcg
Arm/Group Description	Part I was a multiple-ascending dose-escalation in single participant cohorts. RO7172508 was administered intravenously once every 3 weeks (Q3W) at a dose of 65 microgram (mcg).	Part I was a multiple-ascending dose-escalation in single participant cohorts. RO7172508 was administered intravenously once every 3 weeks (Q3W) at a dose of 160 microgram (mcg).	Part I was a multiple-ascending dose-escalation in single participant cohorts. RO7172508 was administered intravenously once every 3 weeks (Q3W) at a dose of 400 microgram (mcg). Part II was a multiple ascending dose-escalation of IV-administered RO7172508 in multiple participant cohorts: The starting-dose for the initiation of the IV dose-escalation was determined by Part I and RO7172508 was initially given Q3W. Starting dose of RO7172508 was 400 mcg.	Part II was a multiple ascending dose-escalation of IV-administered RO7172508 in multiple participant cohorts. RO7172508 was administered intravenously at a dose of 800 mcg.	Part II was a multiple ascending dose-escalation of IV-administered RO7172508 in multiple participant cohorts. RO7172508 was administered intravenously at a dose of 1200 mcg.	Part II was a multiple ascending dose-escalation of IV-administered RO7172508 in multiple participant cohorts. RO7172508 was administered intravenously at a dose of 1800 mcg.
Measure Participants	1	1	4	13	5	2
Baseline sCEA <=20 ng/mL	9.19	21.5	73.3 (54.4)	252 (138)	370 (29.2)	937
Baseline sCEA >20 ng/mL	85.0 (17.3)	184 (167)	290 (2.9)	1180

4. Secondary Outcome

Title	Time of Maximum Concentration of RO7172508
Time Frame	Cycle 1 following single dose administration of RO7172508

Outcome Measure Data

Analysis Population Description

Pharmacokinetic population included all participants who received at least one dose of study treatment and who had data from at least one post-dose sample.

Arm/Group Title	Part I: Single Participant Cohort IV RO7172508 65 mcg	Part I: Single Participant Cohort IV RO7172508 160 mcg	Part I and Part II: Participant Cohorts IV 400 mcg	Part II: Multiple Participant Cohorts IV 800 mcg	Part II: Multiple Participant Cohorts IV 1200 mcg	Part II: Multiple Participant Cohorts IV 1800 mcg
Arm/Group Description	Part I was a multiple-ascending dose-escalation in single participant cohorts. RO7172508 was administered intravenously once every 3 weeks (Q3W) at a dose of 65 microgram (mcg).	Part I was a multiple-ascending dose-escalation in single participant cohorts. RO7172508 was administered intravenously once every 3 weeks (Q3W) at a dose of 160 microgram (mcg).	Part I was a multiple-ascending dose-escalation in single participant cohorts. RO7172508 was administered intravenously once every 3 weeks (Q3W) at a dose of 400 microgram (mcg). Part II was a multiple ascending dose-escalation of IV-administered RO7172508 in multiple participant cohorts: The starting-dose for the initiation of the IV dose-escalation was determined by Part I and RO7172508 was initially given Q3W. Starting dose of RO7172508 was 400 mcg.	Part II was a multiple ascending dose-escalation of IV-administered RO7172508 in multiple participant cohorts. RO7172508 was administered intravenously at a dose of 800 mcg.	Part II was a multiple ascending dose-escalation of IV-administered RO7172508 in multiple participant cohorts. RO7172508 was administered intravenously at a dose of 1200 mcg.	Part II was a multiple ascending dose-escalation of IV-administered RO7172508 in multiple participant cohorts. RO7172508 was administered intravenously at a dose of 1800 mcg.
Measure Participants	1	1	4	13	5	2
Baseline sCEA <=20 ng/mL	2.58	2.07	3.30	3.79	2.13	4.48
Baseline sCEA >20 ng/mL	2.16	2.18	3.09	1.95

5. Secondary Outcome

Title	Clearance or Apparent Clearance of RO7172508
Time Frame	Cycle 1 following single dose administration of RO7172508

Outcome Measure Data

Analysis Population Description

Pharmacokinetic population included all participants who received at least one dose of study treatment and who had data from at least one post-dose sample.

Arm/Group Title	Part I: Single Participant Cohort IV RO7172508 65 mcg	Part I: Single Participant Cohort IV RO7172508 160 mcg	Part I and Part II: Participant Cohorts IV 400 mcg	Part II: Multiple Participant Cohorts IV 800 mcg	Part II: Multiple Participant Cohorts IV 1200 mcg	Part II: Multiple Participant Cohorts IV 1800 mcg
Arm/Group Description	Part I was a multiple-ascending dose-escalation in single participant cohorts. RO7172508 was administered intravenously once every 3 weeks (Q3W) at a dose of 65 microgram (mcg).	Part I was a multiple-ascending dose-escalation in single participant cohorts. RO7172508 was administered intravenously once every 3 weeks (Q3W) at a dose of 160 microgram (mcg).	Part I was a multiple-ascending dose-escalation in single participant cohorts. RO7172508 was administered intravenously once every 3 weeks (Q3W) at a dose of 400 microgram (mcg). Part II was a multiple ascending dose-escalation of IV-administered RO7172508 in multiple participant cohorts: The starting-dose for the initiation of the IV dose-escalation was determined by Part I and RO7172508 was initially given Q3W. Starting dose of RO7172508 was 400 mcg.	Part II was a multiple ascending dose-escalation of IV-administered RO7172508 in multiple participant cohorts. RO7172508 was administered intravenously at a dose of 800 mcg.	Part II was a multiple ascending dose-escalation of IV-administered RO7172508 in multiple participant cohorts. RO7172508 was administered intravenously at a dose of 1200 mcg.	Part II was a multiple ascending dose-escalation of IV-administered RO7172508 in multiple participant cohorts. RO7172508 was administered intravenously at a dose of 1800 mcg.
Measure Participants	1	1	3	8	4	2
Baseline sCEA <=20 ng/mL	332	NA	111 (34.4)	55.4 (61.5)	67.4 (49.2)	34.8
Baseline sCEA >20 ng/mL	453	340 (527)	68.8	39.3

6. Secondary Outcome

Title	Volume of Distribution at Steady State of RO7172508
Time Frame	Cycle 1 following single dose administration of RO7172508

Outcome Measure Data

Analysis Population Description

Analysis not conducted due to participants not reaching steady state due to early withdrawal or loss of exposure due to immunogenicity.

Arm/Group Title	Part I: Single Participant Cohort IV RO7172508 65 mcg	Part I: Single Participant Cohort IV RO7172508 160 mcg	Part I and Part II: Participant Cohorts IV 400 mcg	Part II: Multiple Participant Cohorts IV 800 mcg	Part II: Multiple Participant Cohorts IV 1200 mcg	Part II: Multiple Participant Cohorts IV 1800 mcg
Arm/Group Description	Part I was a multiple-ascending dose-escalation in single participant cohorts. RO7172508 was administered intravenously once every 3 weeks (Q3W) at a dose of 65 microgram (mcg).	Part I was a multiple-ascending dose-escalation in single participant cohorts. RO7172508 was administered intravenously once every 3 weeks (Q3W) at a dose of 160 microgram (mcg).	Part I was a multiple-ascending dose-escalation in single participant cohorts. RO7172508 was administered intravenously once every 3 weeks (Q3W) at a dose of 400 microgram (mcg). Part II was a multiple ascending dose-escalation of IV-administered RO7172508 in multiple participant cohorts: The starting-dose for the initiation of the IV dose-escalation was determined by Part I and RO7172508 was initially given Q3W. Starting dose of RO7172508 was 400 mcg.	Part II was a multiple ascending dose-escalation of IV-administered RO7172508 in multiple participant cohorts. RO7172508 was administered intravenously at a dose of 800 mcg.	Part II was a multiple ascending dose-escalation of IV-administered RO7172508 in multiple participant cohorts. RO7172508 was administered intravenously at a dose of 1200 mcg.	Part II was a multiple ascending dose-escalation of IV-administered RO7172508 in multiple participant cohorts. RO7172508 was administered intravenously at a dose of 1800 mcg.
Measure Participants	0	0	0	0	0	0

7. Secondary Outcome

Title	Area Under the Plasma Concentration Time-Curve From Zero to the Last Measured Concentration (AUClast) of RO7172508
Time Frame	Cycle 1 following single dose administration of RO7172508

Outcome Measure Data

Analysis Population Description

Pharmacokinetic population included all participants who received at least one dose of study treatment and who had data from at least one post-dose sample.

Arm/Group Title	Part I: Single Participant Cohort IV RO7172508 65 mcg	Part I: Single Participant Cohort IV RO7172508 160 mcg	Part I and Part II: Participant Cohorts IV 400 mcg	Part II: Multiple Participant Cohorts IV 800 mcg	Part II: Multiple Participant Cohorts IV 1200 mcg	Part II: Multiple Participant Cohorts IV 1800 mcg
Arm/Group Description	Part I was a multiple-ascending dose-escalation in single participant cohorts. RO7172508 was administered intravenously once every 3 weeks (Q3W) at a dose of 65 microgram (mcg).	Part I was a multiple-ascending dose-escalation in single participant cohorts. RO7172508 was administered intravenously once every 3 weeks (Q3W) at a dose of 160 microgram (mcg).	Part I was a multiple-ascending dose-escalation in single participant cohorts. RO7172508 was administered intravenously once every 3 weeks (Q3W) at a dose of 400 microgram (mcg). Part II was a multiple ascending dose-escalation of IV-administered RO7172508 in multiple participant cohorts: The starting-dose for the initiation of the IV dose-escalation was determined by Part I and RO7172508 was initially given Q3W. Starting dose of RO7172508 was 400 mcg.	Part II was a multiple ascending dose-escalation of IV-administered RO7172508 in multiple participant cohorts. RO7172508 was administered intravenously at a dose of 800 mcg.	Part II was a multiple ascending dose-escalation of IV-administered RO7172508 in multiple participant cohorts. RO7172508 was administered intravenously at a dose of 1200 mcg.	Part II was a multiple ascending dose-escalation of IV-administered RO7172508 in multiple participant cohorts. RO7172508 was administered intravenously at a dose of 1800 mcg.
Measure Participants	1	1	4	13	5	2
Baseline sCEA <=20 ng/mL	6.93	1.91	143 (38.4)	411 (137)	740 (49.4)	2140
Baseline sCEA >20 ng/mL	45.4 (34.4)	83.5 (178)	370 (121)	1910

8. Secondary Outcome

Title	Area Under the Serum Concentration Versus Time Curve Computed From Time of Dosing to Infinity (AUCinf) of RO7172508
Time Frame	Cycle 1 following single dose administration of RO7172508

Outcome Measure Data

Analysis Population Description

Pharmacokinetic population included all participants who received at least one dose of study treatment and who had data from at least one post-dose sample.

Arm/Group Title	Part I: Single Participant Cohort IV RO7172508 65 mcg	Part I: Single Participant Cohort IV RO7172508 160 mcg	Part I and Part II: Participant Cohorts IV 400 mcg	Part II: Multiple Participant Cohorts IV 800 mcg	Part II: Multiple Participant Cohorts IV 1200 mcg	Part II: Multiple Participant Cohorts IV 1800 mcg
Arm/Group Description	Part I was a multiple-ascending dose-escalation in single participant cohorts. RO7172508 was administered intravenously once every 3 weeks (Q3W) at a dose of 65 microgram (mcg).	Part I was a multiple-ascending dose-escalation in single participant cohorts. RO7172508 was administered intravenously once every 3 weeks (Q3W) at a dose of 160 microgram (mcg).	Part I was a multiple-ascending dose-escalation in single participant cohorts. RO7172508 was administered intravenously once every 3 weeks (Q3W) at a dose of 400 microgram (mcg). Part II was a multiple ascending dose-escalation of IV-administered RO7172508 in multiple participant cohorts: The starting-dose for the initiation of the IV dose-escalation was determined by Part I and RO7172508 was initially given Q3W. Starting dose of RO7172508 was 400 mcg.	Part II was a multiple ascending dose-escalation of IV-administered RO7172508 in multiple participant cohorts. RO7172508 was administered intravenously at a dose of 800 mcg.	Part II was a multiple ascending dose-escalation of IV-administered RO7172508 in multiple participant cohorts. RO7172508 was administered intravenously at a dose of 1200 mcg.	Part II was a multiple ascending dose-escalation of IV-administered RO7172508 in multiple participant cohorts. RO7172508 was administered intravenously at a dose of 1800 mcg.
Measure Participants	1	1	3	8	4	2
Baseline sCEA <=20 ng/mL	8.15	NA	150 (34.7)	602 (61.7)	740 (49.2)	2160
Baseline sCEA >20 ng/mL	36.8	98.1 (527)	727	1910

9. Secondary Outcome

Title	Dose Normalized Area Under the Serum Concentration Versus Time Curve Computed From Time of Dosing to Infinity (AUCinf/Dose) of RO7172508
Time Frame	Cycle 1 following single dose administration of RO7172508

Outcome Measure Data

Analysis Population Description

Pharmacokinetic population included all participants who received at least one dose of study treatment and who had data from at least one post-dose sample.

Arm/Group Title	Part I: Single Participant Cohort IV RO7172508 65 mcg	Part I: Single Participant Cohort IV RO7172508 160 mcg	Part I and Part II: Participant Cohorts IV 400 mcg	Part II: Multiple Participant Cohorts IV 800 mcg	Part II: Multiple Participant Cohorts IV 1200 mcg	Part II: Multiple Participant Cohorts IV 1800 mcg
Arm/Group Description	Part I was a multiple-ascending dose-escalation in single participant cohorts. RO7172508 was administered intravenously once every 3 weeks (Q3W) at a dose of 65 microgram (mcg).	Part I was a multiple-ascending dose-escalation in single participant cohorts. RO7172508 was administered intravenously once every 3 weeks (Q3W) at a dose of 160 microgram (mcg).	Part I was a multiple-ascending dose-escalation in single participant cohorts. RO7172508 was administered intravenously once every 3 weeks (Q3W) at a dose of 400 microgram (mcg). Part II was a multiple ascending dose-escalation of IV-administered RO7172508 in multiple participant cohorts: The starting-dose for the initiation of the IV dose-escalation was determined by Part I and RO7172508 was initially given Q3W. Starting dose of RO7172508 was 400 mcg.	Part II was a multiple ascending dose-escalation of IV-administered RO7172508 in multiple participant cohorts. RO7172508 was administered intravenously at a dose of 800 mcg.	Part II was a multiple ascending dose-escalation of IV-administered RO7172508 in multiple participant cohorts. RO7172508 was administered intravenously at a dose of 1200 mcg.	Part II was a multiple ascending dose-escalation of IV-administered RO7172508 in multiple participant cohorts. RO7172508 was administered intravenously at a dose of 1800 mcg.
Measure Participants	1	1	3	8	4	2
Baseline sCEA <=20 ng/mL	125	NA	375 (34.2)	753 (61.6)	618 (49.3)	1200
Baseline sCEA >20 ng/mL	92.0	122 (526)	606	1060

10. Secondary Outcome

Title	Half-Life of RO7172508
Time Frame	Cycle 1 following single dose administration of RO7172508

Outcome Measure Data

Analysis Population Description

Pharmacokinetic population included all participants who received at least one dose of study treatment and who had data from at least one post-dose sample.

Arm/Group Title	Part I: Single Participant Cohort IV RO7172508 65 mcg	Part I: Single Participant Cohort IV RO7172508 160 mcg	Part I and Part II: Participant Cohorts IV 400 mcg	Part II: Multiple Participant Cohorts IV 800 mcg	Part II: Multiple Participant Cohorts IV 1200 mcg	Part II: Multiple Participant Cohorts IV 1800 mcg
Arm/Group Description	Part I was a multiple-ascending dose-escalation in single participant cohorts. RO7172508 was administered intravenously once every 3 weeks (Q3W) at a dose of 65 microgram (mcg).	Part I was a multiple-ascending dose-escalation in single participant cohorts. RO7172508 was administered intravenously once every 3 weeks (Q3W) at a dose of 160 microgram (mcg).	Part I was a multiple-ascending dose-escalation in single participant cohorts. RO7172508 was administered intravenously once every 3 weeks (Q3W) at a dose of 400 microgram (mcg). Part II was a multiple ascending dose-escalation of IV-administered RO7172508 in multiple participant cohorts: The starting-dose for the initiation of the IV dose-escalation was determined by Part I and RO7172508 was initially given Q3W. Starting dose of RO7172508 was 400 mcg.	Part II was a multiple ascending dose-escalation of IV-administered RO7172508 in multiple participant cohorts. RO7172508 was administered intravenously at a dose of 800 mcg.	Part II was a multiple ascending dose-escalation of IV-administered RO7172508 in multiple participant cohorts. RO7172508 was administered intravenously at a dose of 1200 mcg.	Part II was a multiple ascending dose-escalation of IV-administered RO7172508 in multiple participant cohorts. RO7172508 was administered intravenously at a dose of 1800 mcg.
Measure Participants	1	1	3	8	4	2
Baseline sCEA <=20 ng/mL	17.1	NA	54.0 (112)	62.1 (42.4)	40.9 (68.9)	48.7
Baseline sCEA >20 ng/mL	9.27	22.0 (43.9)	23.3	18.4

11. Secondary Outcome

Title	Presence or Absence and Titer of ADAs
Time Frame	Up to approximately 12 months

Outcome Measure Data

Analysis Population Description

Participants were considered as evaluable for immunogenicity analysis if they had at least 3 cycles of treatment to allow for development of potential ADAs.

Arm/Group Title	Part I: Single Participant Cohort IV RO7172508 65 mcgEdit	Part I: Single Participant Cohort IV RO7172508 160 mcg	Part I: Single Participant Cohort IV RO7172508 400 mcg	Part II: Multiple Participant Cohorts IV 400 mcg	Part II: Multiple Participant Cohorts IV 800 mcg	Part II: Multiple Participant Cohorts IV 1200 mcg	Part II: Multiple Participant Cohorts IV 1800 mcg
Arm/Group Description	Part I was a multiple-ascending dose-escalation in single participant cohorts. RO7172508 was administered intravenously once every 3 weeks (Q3W) at a dose of 65 microgram (mcg).	Part I was a multiple-ascending dose-escalation in single participant cohorts. RO7172508 was administered intravenously once every 3 weeks (Q3W) at a dose of 160 microgram (mcg).	Part I was a multiple-ascending dose-escalation in single participant cohorts. RO7172508 was administered intravenously once every 3 weeks (Q3W) at a dose of 400 microgram (mcg).	Part II was a multiple ascending dose-escalation of IV-administered RO7172508 in multiple participant cohorts: The starting-dose for the initiation of the IV dose-escalation was determined by Part I and RO7172508 was initially given Q3W. Starting dose of RO7172508 was 400 mcg.	Part II was a multiple ascending dose-escalation of IV-administered RO7172508 in multiple participant cohorts. RO7172508 was administered intravenously at a dose of 800 mcg.	Part II was a multiple ascending dose-escalation of IV-administered RO7172508 in multiple participant cohorts. RO7172508 was administered intravenously at a dose of 1200 mcg.	Part II was a multiple ascending dose-escalation of IV-administered RO7172508 in multiple participant cohorts. RO7172508 was administered intravenously at a dose of 1800 mcg.
Measure Participants	1	1	1	3	13	5	2
Presence of ADAs	0 0%	0 0%	1 100%	3 100%	5 38.5%	2 40%	0 0%
Positive Titer	0 0%	0 0%	1 100%	3 100%	5 38.5%	2 40%	0 0%

12. Secondary Outcome

Title	Changes in Frequency of Tumor Infiltrating Lymphocytes
Time Frame	Cycle 1 Day 1 (Pre-treatment), Cycle 2 Day 8 (Cycle is 21 days)

Outcome Measure Data

Analysis Population Description

Biopsies were not mandatory in part 1. Results from 2 participants are excluded as measured using a different assay.

Arm/Group Title	Part I: Single Participant Cohort IV RO7172508 65 mcg	Part I: Single Participant Cohort IV RO7172508 160 mcg	Part I: Single Participant Cohort IV RO7172508 400 mcg	Part II: Multiple Participant Cohorts IV 400 mcg	Part II: Multiple Participant Cohorts IV 800 mcg	Part II: Multiple Participant Cohorts IV 1200 mcg	Part II: Multiple Participant Cohorts IV 1800 mcg
Arm/Group Description	Part I was a multiple-ascending dose-escalation in single participant cohorts. RO7172508 was administered intravenously once every 3 weeks (Q3W) at a dose of 65 microgram (mcg).	Part I was a multiple-ascending dose-escalation in single participant cohorts. RO7172508 was administered intravenously once every 3 weeks (Q3W) at a dose of 160 microgram (mcg).	Part I was a multiple-ascending dose-escalation in single participant cohorts. RO7172508 was administered intravenously once every 3 weeks (Q3W) at a dose of 400 microgram (mcg).	Part II was a multiple ascending dose-escalation of IV-administered RO7172508 in multiple participant cohorts: The starting-dose for the initiation of the IV dose-escalation was determined by Part I and RO7172508 was initially given Q3W. Starting dose of RO7172508 was 400 mcg.	Part II was a multiple ascending dose-escalation of IV-administered RO7172508 in multiple participant cohorts. RO7172508 was administered intravenously at a dose of 800 mcg.	Part II was a multiple ascending dose-escalation of IV-administered RO7172508 in multiple participant cohorts. RO7172508 was administered intravenously at a dose of 1200 mcg.	Part II was a multiple ascending dose-escalation of IV-administered RO7172508 in multiple participant cohorts. RO7172508 was administered intravenously at a dose of 1800 mcg.
Measure Participants	1	1	1	3	13	5	2
Measure Results	0	0	0	2	9	3	0
CD8 TIL Pre-treatment (Cycle 1 Day 1)	48.2	41.40	64.4
CD8 TIL On-treatment (Cycle 2 Day 8)	54.15	54.7	52.75
CD4 TIL Pre-treatment (Cycle 1 Day 1)	39.7	35.70	22.90
CD4 TIL On-treatment (Cycle 2 Day 8)	35.00	33.80	42.65

13. Secondary Outcome

Title	Secondary: Changes in Activation Status of Tumor Infiltrating Lymphocytes (% of CD8)
Time Frame	Cycle 1 Day 1 (Pre-treatment), Cycle 2 Day 8 (Cycle is 21 days)

Outcome Measure Data

Analysis Population Description

Biopsies were not mandatory in part 1. Results from 2 participants are excluded as measured using a different assay.

Arm/Group Title	Part I: Single Participant Cohort IV RO7172508 65 mcg	Part I: Single Participant Cohort IV RO7172508 160 mcg	Part I: Single Participant Cohort IV RO7172508 400 mcg	Part II: Multiple Participant Cohorts IV 400 mcg	Part II: Multiple Participant Cohorts IV 800 mcg	Part II: Multiple Participant Cohorts IV 1200 mcg	Part II: Multiple Participant Cohorts IV 1800 mcg
Arm/Group Description	Part I was a multiple-ascending dose-escalation in single participant cohorts. RO7172508 was administered intravenously once every 3 weeks (Q3W) at a dose of 65 microgram (mcg).	Part I was a multiple-ascending dose-escalation in single participant cohorts. RO7172508 was administered intravenously once every 3 weeks (Q3W) at a dose of 160 microgram (mcg).	Part I was a multiple-ascending dose-escalation in single participant cohorts. RO7172508 was administered intravenously once every 3 weeks (Q3W) at a dose of 400 microgram (mcg).	Part II was a multiple ascending dose-escalation of IV-administered RO7172508 in multiple participant cohorts: The starting-dose for the initiation of the IV dose-escalation was determined by Part I and RO7172508 was initially given Q3W. Starting dose of RO7172508 was 400 mcg.	Part II was a multiple ascending dose-escalation of IV-administered RO7172508 in multiple participant cohorts. RO7172508 was administered intravenously at a dose of 800 mcg.	Part II was a multiple ascending dose-escalation of IV-administered RO7172508 in multiple participant cohorts. RO7172508 was administered intravenously at a dose of 1200 mcg.	Part II was a multiple ascending dose-escalation of IV-administered RO7172508 in multiple participant cohorts. RO7172508 was administered intravenously at a dose of 1800 mcg.
Measure Participants	1	1	1	3	13	5	2
Measure Results	0	0	0	2	9	3	0
CD8+CD25+ Pre-treatment (Cycle 1 Day 1)	22.00	17.60	9.70
CD8+CD25+ On-treatment (Cycle 2 Day 8)	25.80	35.30	19.60
CD8+CD279+ Pre-treatment (Cycle 1 Day 1)	11.90	8.70	11.40
CD8+CD279+ On-treatment (Cycle 2 Day 8)	16.80	23.20	7.90

14. Secondary Outcome

Title	Changes in Activation Status of Tumor Infiltrating Lymphocytes (% of CD4)
Time Frame	Cycle 1 Day 1 (Pre-treatment), Cycle 2 Day 8 (Cycle is 21 days)

Outcome Measure Data

Analysis Population Description

Biopsies were not mandatory in part 1. Results from 2 participants are excluded as measured using a different assay.

Arm/Group Title	Part I: Single Participant Cohort IV RO7172508 65 mcg	Part I: Single Participant Cohort IV RO7172508 160 mcg	Part I: Single Participant Cohort IV RO7172508 400 mcg	Part II: Multiple Participant Cohorts IV 400 mcg	Part II: Multiple Participant Cohorts IV 800 mcg	Part II: Multiple Participant Cohorts IV 1200 mcg	Part II: Multiple Participant Cohorts IV 1800 mcg
Arm/Group Description	Part I was a multiple-ascending dose-escalation in single participant cohorts. RO7172508 was administered intravenously once every 3 weeks (Q3W) at a dose of 65 microgram (mcg).	Part I was a multiple-ascending dose-escalation in single participant cohorts. RO7172508 was administered intravenously once every 3 weeks (Q3W) at a dose of 160 microgram (mcg).	Part I was a multiple-ascending dose-escalation in single participant cohorts. RO7172508 was administered intravenously once every 3 weeks (Q3W) at a dose of 400 microgram (mcg).	Part II was a multiple ascending dose-escalation of IV-administered RO7172508 in multiple participant cohorts: The starting-dose for the initiation of the IV dose-escalation was determined by Part I and RO7172508 was initially given Q3W. Starting dose of RO7172508 was 400 mcg.	Part II was a multiple ascending dose-escalation of IV-administered RO7172508 in multiple participant cohorts. RO7172508 was administered intravenously at a dose of 800 mcg.	Part II was a multiple ascending dose-escalation of IV-administered RO7172508 in multiple participant cohorts. RO7172508 was administered intravenously at a dose of 1200 mcg.	Part II was a multiple ascending dose-escalation of IV-administered RO7172508 in multiple participant cohorts. RO7172508 was administered intravenously at a dose of 1800 mcg.
Measure Participants	1	1	1	3	13	5	2
Measure Results	0	0	0	2	9	3	0
CD4+CD25+ Pre-treatment (Cycle 1 Day 1)	51.9	41.20	26.90
CD4+CD25+ On-treatment (Cycle 2 Day 8)	47.35	47.65	30.75
CD4+CD279+ Pre-treatment (Cycle 1 Day 1)	16.50	10.90	16.80
CD4+CD279+ On-treatment (Cycle 2 Day 8)	27.40	24.30	22.40

15. Secondary Outcome

Title	Changes in Spatial Distribution of Tumor Infiltrating Lymphocytes
Description	Spatial distribution of TIL's analyzed by performing IHC assay, which measures the density and intra-tumoral location of CD8+ T cells and reports "CD8 T cell immune phenotypes". These are classified as "desert", "excluded" and "inflamed".
Time Frame	Cycle 1 Day 1 (Pre-treatment), Cycle 2 Day 8 (Cycle is 21 days)

Outcome Measure Data

Analysis Population Description

Paired included participant's with different dose and actual exposure levels. Data were pooled across all dose levels because the number of biopsy evaluable participants was overall small, and no dose/response relationship was found.

Arm/Group Title	Part I: Single Participant Cohort IV RO7172508 65 mcg	Part I: Single Participant Cohort IV RO7172508 160 mcg	Part I: Single Participant Cohort IV RO7172508 400 mcg	Part II: Multiple Participant Cohorts IV 400 mcg	Part II: Multiple Participant Cohorts IV 800 mcg	Part II: Multiple Participant Cohorts IV 1200 mcg	Part II: Multiple Participant Cohorts IV 1800 mcg
Arm/Group Description	Part I was a multiple-ascending dose-escalation in single participant cohorts. RO7172508 was administered intravenously once every 3 weeks (Q3W) at a dose of 65 microgram (mcg).	Part I was a multiple-ascending dose-escalation in single participant cohorts. RO7172508 was administered intravenously once every 3 weeks (Q3W) at a dose of 160 microgram (mcg).	Part I was a multiple-ascending dose-escalation in single participant cohorts. RO7172508 was administered intravenously once every 3 weeks (Q3W) at a dose of 400 microgram (mcg).	Part II was a multiple ascending dose-escalation of IV-administered RO7172508 in multiple participant cohorts: The starting-dose for the initiation of the IV dose-escalation was determined by Part I and RO7172508 was initially given Q3W. Starting dose of RO7172508 was 400 mcg.	Part II was a multiple ascending dose-escalation of IV-administered RO7172508 in multiple participant cohorts. RO7172508 was administered intravenously at a dose of 800 mcg.	Part II was a multiple ascending dose-escalation of IV-administered RO7172508 in multiple participant cohorts. RO7172508 was administered intravenously at a dose of 1200 mcg.	Part II was a multiple ascending dose-escalation of IV-administered RO7172508 in multiple participant cohorts. RO7172508 was administered intravenously at a dose of 1800 mcg.
Measure Participants	1	1	1	3	13	5	2
Measure Results	0	0	0	2	9	4	2
Pre-treatment (Cycle 1 Day 1) Desert	1	5	0	0
Pre-treatment (Cycle 1 Day 1) Excluded	0	0	1	1
Pre-treatment (Cycle 1 Day 1) Inflamed	0	2	1	1
On-treatment (Cycle 2 Day 8) Desert	2	6	1
On-treatment (Cycle 2 Day 8) Excluded	0	1	2
On-treatment (Cycle 2 Day 8) Inflamed	0	2	1

16. Secondary Outcome

Title	Objective Response Rate (ORR)
Description	Objective response was defined as a Complete Response (CR) or Parital Response (PR), as determined by the Investigator's assessment using RECIST v1.1 and confirmed by repeat assessments >= 4 weeks after initial documentation. To classify a response as SD, measurements are classified as stable (according to RECIST v1.1) at least once after study entry at a minimum of 6 weeks after study entry.
Time Frame	Up to approximately 12 months

Outcome Measure Data

Analysis Population Description

Efficacy population included all participants who received at least one dose of RO7172508.

Arm/Group Title	Part I: Single Participant Cohort IV RO7172508 65 mcg	Part I: Single Participant Cohort IV RO7172508 160 mcg	Part I: Single Participant Cohort IV RO7172508 400 mcg	Part II: Multiple Participant Cohorts IV 400 mcg	Part II: Multiple Participant Cohorts IV 800 mcg	Part II: Multiple Participant Cohorts IV 1200 mcg	Part II: Multiple Participant Cohorts IV 1800 mcg
Arm/Group Description	Part I was a multiple-ascending dose-escalation in single participant cohorts. RO7172508 was administered intravenously once every 3 weeks (Q3W) at a dose of 65 microgram (mcg).	Part I was a multiple-ascending dose-escalation in single participant cohorts. RO7172508 was administered intravenously once every 3 weeks (Q3W) at a dose of 160 microgram (mcg).	Part I was a multiple-ascending dose-escalation in single participant cohorts. RO7172508 was administered intravenously once every 3 weeks (Q3W) at a dose of 400 microgram (mcg).	Part II was a multiple ascending dose-escalation of IV-administered RO7172508 in multiple participant cohorts: The starting-dose for the initiation of the IV dose-escalation was determined by Part I and RO7172508 was initially given Q3W. Starting dose of RO7172508 was 400 mcg.	Part II was a multiple ascending dose-escalation of IV-administered RO7172508 in multiple participant cohorts. RO7172508 was administered intravenously at a dose of 800 mcg.	Part II was a multiple ascending dose-escalation of IV-administered RO7172508 in multiple participant cohorts. RO7172508 was administered intravenously at a dose of 1200 mcg.	Part II was a multiple ascending dose-escalation of IV-administered RO7172508 in multiple participant cohorts. RO7172508 was administered intravenously at a dose of 1800 mcg.
Measure Participants	1	1	1	3	13	5	2
Number [Participants]	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%

17. Secondary Outcome

Title	Disease Control Rate (DCR)
Description	DCR is determined as the rate of participants with an observed tumor response of CR or PR (ORR) or CR, PR or SD (DCR). DCR is to be derived for RECIST v1.1.
Time Frame	Up to approximately 12 months

Outcome Measure Data

Analysis Population Description

Efficacy population included all participants who received at least one dose of RO7172508.

Arm/Group Title	Part I: Single Participant Cohort IV RO7172508 65 mcg	Part I: Single Participant Cohort IV RO7172508 160 mcg	Part I: Single Participant Cohort IV RO7172508 400 mcg	Part II: Multiple Participant Cohorts IV 400 mcg	Part II: Multiple Participant Cohorts IV 800 mcg	Part II: Multiple Participant Cohorts IV 1200 mcg	Part II: Multiple Participant Cohorts IV 1800 mcg
Arm/Group Description	Part I was a multiple-ascending dose-escalation in single participant cohorts. RO7172508 was administered intravenously once every 3 weeks (Q3W) at a dose of 65 microgram (mcg).	Part I was a multiple-ascending dose-escalation in single participant cohorts. RO7172508 was administered intravenously once every 3 weeks (Q3W) at a dose of 160 microgram (mcg).	Part I was a multiple-ascending dose-escalation in single participant cohorts. RO7172508 was administered intravenously once every 3 weeks (Q3W) at a dose of 400 microgram (mcg).	Part II was a multiple ascending dose-escalation of IV-administered RO7172508 in multiple participant cohorts: The starting-dose for the initiation of the IV dose-escalation was determined by Part I and RO7172508 was initially given Q3W. Starting dose of RO7172508 was 400 mcg.	Part II was a multiple ascending dose-escalation of IV-administered RO7172508 in multiple participant cohorts. RO7172508 was administered intravenously at a dose of 800 mcg.	Part II was a multiple ascending dose-escalation of IV-administered RO7172508 in multiple participant cohorts. RO7172508 was administered intravenously at a dose of 1200 mcg.	Part II was a multiple ascending dose-escalation of IV-administered RO7172508 in multiple participant cohorts. RO7172508 was administered intravenously at a dose of 1800 mcg.
Measure Participants	1	1	1	3	13	5	2
Count of Participants [Participants]	0 0%	0 0%	0 0%	1 33.3%	3 23.1%	1 20%	0 0%

18. Secondary Outcome

Title	Duration of Response (DOR)
Description	Among participants with an objective response (responders), DOR will be defined as the time from first occurrence of a documented objective response until the time of documented disease progression or death within 30 days from last study treatment from any cause during treatment, whichever occurs first. This will be calculated for participants who have a best overall response of CR or PR as defined per RECIST v1.1 and per iRECIST.
Time Frame	Up to approximately 12 month

Outcome Measure Data

Analysis Population Description

Efficacy population included all participants who received at least one dose of RO7172508. DOR was not calculated because none of the participants had a response (complete or partial).

Arm/Group Title	Part I: Single Participant Cohort IV RO7172508 65 mcg	Part I: Single Participant Cohort IV RO7172508 160 mcg	Part I: Single Participant Cohort IV RO7172508 400 mcg	Part II: Multiple Participant Cohorts IV 400 mcg	Part II: Multiple Participant Cohorts IV 800 mcg	Part II: Multiple Participant Cohorts IV 1200 mcg	Part II: Multiple Participant Cohorts IV 1800 mcg
Arm/Group Description	Part I was a multiple-ascending dose-escalation in single participant cohorts. RO7172508 was administered intravenously once every 3 weeks (Q3W) at a dose of 65 microgram (mcg).	Part I was a multiple-ascending dose-escalation in single participant cohorts. RO7172508 was administered intravenously once every 3 weeks (Q3W) at a dose of 160 microgram (mcg).	Part I was a multiple-ascending dose-escalation in single participant cohorts. RO7172508 was administered intravenously once every 3 weeks (Q3W) at a dose of 400 microgram (mcg).	Part II was a multiple ascending dose-escalation of IV-administered RO7172508 in multiple participant cohorts: The starting-dose for the initiation of the IV dose-escalation was determined by Part I and RO7172508 was initially given Q3W. Starting dose of RO7172508 was 400 mcg.	Part II was a multiple ascending dose-escalation of IV-administered RO7172508 in multiple participant cohorts. RO7172508 was administered intravenously at a dose of 800 mcg.	Part II was a multiple ascending dose-escalation of IV-administered RO7172508 in multiple participant cohorts. RO7172508 was administered intravenously at a dose of 1200 mcg.	Part II was a multiple ascending dose-escalation of IV-administered RO7172508 in multiple participant cohorts. RO7172508 was administered intravenously at a dose of 1800 mcg.
Measure Participants	0	0	0	0	0	0	0

19. Secondary Outcome

Title	Progression Free Survival (PFS)
Description	PFS (on-treatment) will be defined as the time from study treatment initiation (Cycle 1 Day 1) to the first occurrence of documented disease progression or death from any cause during treatment (death within 30 days from last study treatment), whichever occurs first.
Time Frame	Up to approxmately 12 months

Outcome Measure Data

Analysis Population Description

Efficacy population included all participants who received at least one dose of RO7172508. PFS was not calculated because number of evaluable participants in each cohort respectively was too small to obtain reliable estimates for this endpoint.

Arm/Group Title	Part I: Single Participant Cohort IV RO7172508 65 mcg	Part I: Single Participant Cohort IV RO7172508 160 mcg	Part I: Single Participant Cohort IV RO7172508 400 mcg	Part II: Multiple Participant Cohorts IV 400 mcg	Part II: Multiple Participant Cohorts IV 800 mcg	Part II: Multiple Participant Cohorts IV 1200 mcg	Part II: Multiple Participant Cohorts IV 1800 mcg
Arm/Group Description	Part I was a multiple-ascending dose-escalation in single participant cohorts. RO7172508 was administered intravenously once every 3 weeks (Q3W) at a dose of 65 microgram (mcg).	Part I was a multiple-ascending dose-escalation in single participant cohorts. RO7172508 was administered intravenously once every 3 weeks (Q3W) at a dose of 160 microgram (mcg).	Part I was a multiple-ascending dose-escalation in single participant cohorts. RO7172508 was administered intravenously once every 3 weeks (Q3W) at a dose of 400 microgram (mcg).	Part II was a multiple ascending dose-escalation of IV-administered RO7172508 in multiple participant cohorts: The starting-dose for the initiation of the IV dose-escalation was determined by Part I and RO7172508 was initially given Q3W. Starting dose of RO7172508 was 400 mcg.	Part II was a multiple ascending dose-escalation of IV-administered RO7172508 in multiple participant cohorts. RO7172508 was administered intravenously at a dose of 800 mcg.	Part II was a multiple ascending dose-escalation of IV-administered RO7172508 in multiple participant cohorts. RO7172508 was administered intravenously at a dose of 1200 mcg.	Part II was a multiple ascending dose-escalation of IV-administered RO7172508 in multiple participant cohorts. RO7172508 was administered intravenously at a dose of 1800 mcg.
Measure Participants	0	0	0	0	0	0	0

Adverse Events

Time Frame	Baseline up to approximately 12 months
Adverse Event Reporting Description	The safety population included all participants enrolled in the study who received at least one dose of study treatment.
Arm/Group Title	PART1 - RO7172508 - Q3W - 65 mcg		PART1 - RO7172508 - Q3W - 160 mcg		PART1 - RO7172508 - Q3W - 400 mcg		PART2 - RO7172508 - Q3W - 400 mcg		PART2 - RO7172508 - Q3W - 800 mcg		PART2 - RO7172508 - Q3W - 1200 mcg		PART2 - RO7172508 - Q3W - 1800 mcg
Arm/Group Description	Part I was a multiple-ascending dose-escalation in single participant cohorts. RO7172508 was administered intravenously once every 3 weeks (Q3W) at a dose of 65 microgram (mcg).		Part I was a multiple-ascending dose-escalation in single participant cohorts. RO7172508 was administered intravenously once every 3 weeks (Q3W) at a dose of 160 microgram (mcg).		Part I was a multiple-ascending dose-escalation in single participant cohorts. RO7172508 was administered intravenously once every 3 weeks (Q3W) at a dose of 400 microgram (mcg).		Part II was a multiple ascending dose-escalation of IV-administered RO7172508 in multiple participant cohorts: The starting-dose for the initiation of the IV dose-escalation was determined by Part I and RO7172508 was initially given Q3W. Starting dose of RO7172508 was 400 mcg.		Part II was a multiple ascending dose-escalation of IV-administered RO7172508 in multiple participant cohorts. RO7172508 was administered intravenously at a dose of 800 mcg.		Part II was a multiple ascending dose-escalation of IV-administered RO7172508 in multiple participant cohorts. RO7172508 was administered intravenously at a dose of 1200 mcg.		Part II was a multiple ascending dose-escalation of IV-administered RO7172508 in multiple participant cohorts. RO7172508 was administered intravenously at a dose of 1800 mcg.
All Cause Mortality
	PART1 - RO7172508 - Q3W - 65 mcg		PART1 - RO7172508 - Q3W - 160 mcg		PART1 - RO7172508 - Q3W - 400 mcg		PART2 - RO7172508 - Q3W - 400 mcg		PART2 - RO7172508 - Q3W - 800 mcg		PART2 - RO7172508 - Q3W - 1200 mcg		PART2 - RO7172508 - Q3W - 1800 mcg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/1 (100%)		0/1 (0%)		0/1 (0%)		2/3 (66.7%)		8/13 (61.5%)		3/5 (60%)		0/2 (0%)
Serious Adverse Events
	PART1 - RO7172508 - Q3W - 65 mcg		PART1 - RO7172508 - Q3W - 160 mcg		PART1 - RO7172508 - Q3W - 400 mcg		PART2 - RO7172508 - Q3W - 400 mcg		PART2 - RO7172508 - Q3W - 800 mcg		PART2 - RO7172508 - Q3W - 1200 mcg		PART2 - RO7172508 - Q3W - 1800 mcg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/1 (0%)		1/1 (100%)		1/1 (100%)		0/3 (0%)		8/13 (61.5%)		3/5 (60%)		2/2 (100%)
Gastrointestinal disorders
Abdominal pain	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/13 (7.7%)	2	0/5 (0%)	0	0/2 (0%)	0
Diarrhoea	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/13 (7.7%)	1	2/5 (40%)	4	0/2 (0%)	0
Enteritis	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	0/5 (0%)	0	1/2 (50%)	1
Ileus	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/13 (7.7%)	2	0/5 (0%)	0	0/2 (0%)	0
Small intestinal obstruction	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	2/13 (15.4%)	2	0/5 (0%)	0	0/2 (0%)	0
Vomiting	0/1 (0%)	0	0/1 (0%)	0	1/1 (100%)	1	0/3 (0%)	0	1/13 (7.7%)	1	0/5 (0%)	0	0/2 (0%)	0
Hepatobiliary disorders
Cholangitis	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	1/5 (20%)	2	0/2 (0%)	0
Immune system disorders
Cytokine release syndrome	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	0/5 (0%)	0	1/2 (50%)	1
Infections and infestations
Peritonitis	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	1/5 (20%)	1	0/2 (0%)	0
Injury, poisoning and procedural complications
Infusion related reaction	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	2/13 (15.4%)	2	0/5 (0%)	0	1/2 (50%)	1
Investigations
Aspartate aminotransferase increased	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/13 (7.7%)	1	0/5 (0%)	0	0/2 (0%)	0
Blood bilirubin increased	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/13 (7.7%)	1	0/5 (0%)	0	0/2 (0%)	0
Musculoskeletal and connective tissue disorders
Back pain	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/13 (7.7%)	1	0/5 (0%)	0	0/2 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour pain	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/13 (7.7%)	2	0/5 (0%)	0	0/2 (0%)	0
Nervous system disorders
Spinal cord compression	0/1 (0%)	0	1/1 (100%)	1	0/1 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	0/5 (0%)	0	0/2 (0%)	0
Psychiatric disorders
Confusional state	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	1/5 (20%)	2	0/2 (0%)	0
Other (Not Including Serious) Adverse Events
	PART1 - RO7172508 - Q3W - 65 mcg		PART1 - RO7172508 - Q3W - 160 mcg		PART1 - RO7172508 - Q3W - 400 mcg		PART2 - RO7172508 - Q3W - 400 mcg		PART2 - RO7172508 - Q3W - 800 mcg		PART2 - RO7172508 - Q3W - 1200 mcg		PART2 - RO7172508 - Q3W - 1800 mcg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/1 (100%)		1/1 (100%)		1/1 (100%)		3/3 (100%)		13/13 (100%)		5/5 (100%)		2/2 (100%)
Blood and lymphatic system disorders
Anaemia	0/1 (0%)	0	0/1 (0%)	0	1/1 (100%)	1	1/3 (33.3%)	1	6/13 (46.2%)	12	2/5 (40%)	4	0/2 (0%)	0
Cardiac disorders
Sinus tachycardia	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/13 (7.7%)	1	0/5 (0%)	0	0/2 (0%)	0
Ear and labyrinth disorders
Vertigo	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	1/5 (20%)	1	0/2 (0%)	0
Eye disorders
Episcleritis	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	1/5 (20%)	1	0/2 (0%)	0
Eye haematoma	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	1/5 (20%)	1	0/2 (0%)	0
Gastrointestinal disorders
Abdominal pain	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	5/13 (38.5%)	6	0/5 (0%)	0	1/2 (50%)	3
Abdominal pain upper	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/13 (7.7%)	1	2/5 (40%)	2	0/2 (0%)	0
Aerophagia	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	1/5 (20%)	1	0/2 (0%)	0
Constipation	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/13 (7.7%)	1	0/5 (0%)	0	0/2 (0%)	0
Diarrhoea	1/1 (100%)	1	0/1 (0%)	0	1/1 (100%)	2	1/3 (33.3%)	1	3/13 (23.1%)	6	3/5 (60%)	5	2/2 (100%)	4
Dry mouth	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	1/5 (20%)	1	0/2 (0%)	0
Dyspepsia	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/13 (7.7%)	1	0/5 (0%)	0	0/2 (0%)	0
Enteritis	0/1 (0%)	0	0/1 (0%)	0	1/1 (100%)	1	0/3 (0%)	0	0/13 (0%)	0	0/5 (0%)	0	1/2 (50%)	1
Gastrooesophageal reflux disease	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	0/5 (0%)	0	1/2 (50%)	1
Intra-abdominal fluid collection	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	0/5 (0%)	0	1/2 (50%)	1
Nausea	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	1/3 (33.3%)	1	4/13 (30.8%)	7	3/5 (60%)	6	1/2 (50%)	1
Stomatitis	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/13 (7.7%)	1	1/5 (20%)	1	0/2 (0%)	0
Vomiting	0/1 (0%)	0	0/1 (0%)	0	1/1 (100%)	5	1/3 (33.3%)	1	3/13 (23.1%)	8	3/5 (60%)	11	0/2 (0%)	0
General disorders
Asthenia	0/1 (0%)	0	0/1 (0%)	0	1/1 (100%)	1	1/3 (33.3%)	1	2/13 (15.4%)	2	2/5 (40%)	2	0/2 (0%)	0
Chest pain	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	1/5 (20%)	1	0/2 (0%)	0
Chills	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/13 (7.7%)	2	0/5 (0%)	0	0/2 (0%)	0
Early satiety	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/13 (7.7%)	1	0/5 (0%)	0	0/2 (0%)	0
Fatigue	1/1 (100%)	1	0/1 (0%)	0	0/1 (0%)	0	2/3 (66.7%)	2	4/13 (30.8%)	4	2/5 (40%)	2	2/2 (100%)	2
Infusion site extravasation	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	0/5 (0%)	0	1/2 (50%)	1
Non-cardiac chest pain	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/13 (7.7%)	1	0/5 (0%)	0	0/2 (0%)	0
Oedema	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/13 (7.7%)	1	0/5 (0%)	0	0/2 (0%)	0
Oedema peripheral	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/13 (7.7%)	1	2/5 (40%)	2	1/2 (50%)	1
Pyrexia	0/1 (0%)	0	0/1 (0%)	0	1/1 (100%)	3	1/3 (33.3%)	2	4/13 (30.8%)	5	1/5 (20%)	1	0/2 (0%)	0
Infections and infestations
Bacteraemia	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	0/5 (0%)	0	1/2 (50%)	1
Cystitis	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	1/5 (20%)	1	0/2 (0%)	0
Mucosal infection	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	1/3 (33.3%)	2	0/13 (0%)	0	0/5 (0%)	0	0/2 (0%)	0
Nasopharyngitis	0/1 (0%)	0	0/1 (0%)	0	1/1 (100%)	1	0/3 (0%)	0	0/13 (0%)	0	0/5 (0%)	0	0/2 (0%)	0
Paronychia	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	1/3 (33.3%)	1	0/13 (0%)	0	0/5 (0%)	0	0/2 (0%)	0
Pneumonia	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/13 (7.7%)	1	0/5 (0%)	0	0/2 (0%)	0
Respiratory tract infection	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/13 (7.7%)	1	0/5 (0%)	0	0/2 (0%)	0
Skin infection	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/13 (7.7%)	1	1/5 (20%)	1	0/2 (0%)	0
Upper respiratory tract infection	0/1 (0%)	0	0/1 (0%)	0	1/1 (100%)	1	0/3 (0%)	0	0/13 (0%)	0	0/5 (0%)	0	0/2 (0%)	0
Injury, poisoning and procedural complications
Incorrect dose administered	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/13 (7.7%)	1	0/5 (0%)	0	0/2 (0%)	0
Infusion related reaction	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	2/13 (15.4%)	3	1/5 (20%)	1	0/2 (0%)	0
Intercepted medication error	1/1 (100%)	1	0/1 (0%)	0	0/1 (0%)	0	1/3 (33.3%)	1	0/13 (0%)	0	0/5 (0%)	0	0/2 (0%)	0
Toxicity to various agents	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	1/3 (33.3%)	1	0/13 (0%)	0	0/5 (0%)	0	0/2 (0%)	0
Investigations
Alanine aminotransferase increased	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/13 (7.7%)	1	1/5 (20%)	2	0/2 (0%)	0
Amylase increased	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	2/13 (15.4%)	2	0/5 (0%)	0	1/2 (50%)	2
Aspartate aminotransferase increased	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	2/13 (15.4%)	2	1/5 (20%)	2	0/2 (0%)	0
Blood alkaline phosphatase increased	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/13 (7.7%)	2	0/5 (0%)	0	0/2 (0%)	0
Blood bilirubin increased	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/13 (7.7%)	1	0/5 (0%)	0	0/2 (0%)	0
Blood creatinine increased	0/1 (0%)	0	1/1 (100%)	1	0/1 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	1/5 (20%)	1	0/2 (0%)	0
Body temperature increased	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	1/5 (20%)	1	0/2 (0%)	0
Lipase increased	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	2/13 (15.4%)	2	1/5 (20%)	1	1/2 (50%)	1
Lymphocyte count decreased	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/13 (7.7%)	1	0/5 (0%)	0	0/2 (0%)	0
Platelet count decreased	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/13 (7.7%)	3	0/5 (0%)	0	0/2 (0%)	0
Weight decreased	1/1 (100%)	1	0/1 (0%)	0	0/1 (0%)	0	1/3 (33.3%)	1	1/13 (7.7%)	1	0/5 (0%)	0	0/2 (0%)	0
Metabolism and nutrition disorders
Decreased appetite	0/1 (0%)	0	1/1 (100%)	1	0/1 (0%)	0	2/3 (66.7%)	3	5/13 (38.5%)	5	3/5 (60%)	4	1/2 (50%)	1
Dehydration	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	1/5 (20%)	1	1/2 (50%)	1
Hyperphosphataemia	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/13 (7.7%)	1	0/5 (0%)	0	0/2 (0%)	0
Hypoalbuminaemia	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	1/5 (20%)	3	0/2 (0%)	0
Hypokalaemia	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	1/3 (33.3%)	1	4/13 (30.8%)	5	1/5 (20%)	2	1/2 (50%)	3
Hypomagnesaemia	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	0/5 (0%)	0	2/2 (100%)	3
Hyponatraemia	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	2/5 (40%)	2	0/2 (0%)	0
Hypophosphataemia	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	0/5 (0%)	0	1/2 (50%)	2
Musculoskeletal and connective tissue disorders
Arthralgia	0/1 (0%)	0	0/1 (0%)	0	1/1 (100%)	3	1/3 (33.3%)	1	0/13 (0%)	0	0/5 (0%)	0	0/2 (0%)	0
Back pain	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	1/3 (33.3%)	2	1/13 (7.7%)	1	1/5 (20%)	1	0/2 (0%)	0
Muscular weakness	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	0/5 (0%)	0	1/2 (50%)	1
Musculoskeletal chest pain	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	1/5 (20%)	2	0/2 (0%)	0
Myalgia	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	1/3 (33.3%)	1	0/13 (0%)	0	0/5 (0%)	0	0/2 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer pain	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	1/5 (20%)	1	0/2 (0%)	0
Tumour pain	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/13 (7.7%)	3	0/5 (0%)	0	0/2 (0%)	0
Nervous system disorders
Dysgeusia	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	1/3 (33.3%)	1	0/13 (0%)	0	0/5 (0%)	0	0/2 (0%)	0
Headache	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	1/3 (33.3%)	1	0/13 (0%)	0	2/5 (40%)	3	0/2 (0%)	0
Psychiatric disorders
Anxiety	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/13 (7.7%)	1	0/5 (0%)	0	0/2 (0%)	0
Confusional state	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/13 (7.7%)	1	0/5 (0%)	0	0/2 (0%)	0
Depression	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	1/5 (20%)	1	0/2 (0%)	0
Insomnia	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/13 (7.7%)	1	0/5 (0%)	0	0/2 (0%)	0
Renal and urinary disorders
Urinary retention	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	1/5 (20%)	1	0/2 (0%)	0
Respiratory, thoracic and mediastinal disorders
Cough	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/13 (7.7%)	1	0/5 (0%)	0	0/2 (0%)	0
Dysphonia	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	1/5 (20%)	1	0/2 (0%)	0
Dyspnoea	0/1 (0%)	0	1/1 (100%)	1	0/1 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	1/5 (20%)	1	0/2 (0%)	0
Hypoxia	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/13 (7.7%)	1	0/5 (0%)	0	0/2 (0%)	0
Skin and subcutaneous tissue disorders
Decubitus ulcer	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	1/3 (33.3%)	1	0/13 (0%)	0	0/5 (0%)	0	0/2 (0%)	0
Pruritus	0/1 (0%)	0	0/1 (0%)	0	1/1 (100%)	2	0/3 (0%)	0	0/13 (0%)	0	0/5 (0%)	0	0/2 (0%)	0
Rash	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	1/3 (33.3%)	1	2/13 (15.4%)	2	0/5 (0%)	0	0/2 (0%)	0
Vascular disorders
Embolism	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	1/5 (20%)	1	0/2 (0%)	0
Hot flush	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	1/3 (33.3%)	1	0/13 (0%)	0	0/5 (0%)	0	0/2 (0%)	0
Hypertension	0/1 (0%)	0	1/1 (100%)	1	0/1 (0%)	0	0/3 (0%)	0	2/13 (15.4%)	2	0/5 (0%)	0	0/2 (0%)	0
Hypotension	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/13 (7.7%)	1	0/5 (0%)	0	0/2 (0%)	0
Jugular vein thrombosis	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	1/5 (20%)	1	0/2 (0%)	0

Limitations/Caveats

RO7172508 SC not initiated; max tolerated dose IV below starting dose for SC. Study terminated due to change in benefit-risk ratio, driven by high incidence GI toxicity in absence of clinically significant anti-tumor efficacy at dose levels tested.

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.