Sponsor decision to terminate during Phase 1

This is a first-in-human (FIH), phase 1/2, multi center, open-label, dose escalation and cohort expansion study designed to determine the safety and tolerability of PRS-344/S095012 in patients with advanced and/or metastatic solid tumors.

The trial is an open-label, multi-center safety trial of PRS-344/S095012. The trial consists of two parts, a dose escalation part (phase 1, first-in-human (FIH) and an expansion part (phase 2)). The expansion part of the trial will be initiated once the optimal biological dose (OBD) has been determined. The study was terminated during phase 1 and thus, recruitment into phase 2 was not started.

Inclusion Criteria:

1. Age ≥18 years on the day the consent is signed.
2. Patients with histologically confirmed diagnosis of unresectable, locally advanced or metastatic solid tumor for which standard treatment options are not available, no longer effective, or not tolerated.
3. Patient should have a documented disease progression on prior therapy before entry into this study.
4. Patients must have at least one measurable target lesion as per RECIST 1.1.
5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
6. Patient with no available archived material must have one or more tumor lesions amenable to biopsy.
7. Adequate organ function as assessed by laboratory tests within 7 days prior to pretreatment with obinutuzumab.
8. A female patient must use a highly effective method of birth control during study treatment and for 120 days after last dose of PRS-344/S095012, or 18 months after the last obinutuzumab infusion, whichever comes the latest.

Exclusion Criteria:

1. Patients with previously treated brain metastases may participate provided they are radiologically stable, clinically asymptomatic and are off immunosuppressive therapies for at least 4 weeks. Low dose of steroid <10 mg/day prednisone or equivalent) is allowed.

2. Patients who have received prior:

   1. Small molecule inhibitors, and/or other similar investigational agent: ≤ 2 weeks or 5 half-lives, whichever is shorter.
   2. Chemotherapy, other monoclonal antibodies, antibody-drug conjugates, or other similar experimental therapies: ≤3 weeks or 5 half-lives, whichever is shorter.
   3. Radioimmunoconjugates or other similar experimental therapies ≤6 weeks or 5 half-lives, whichever is shorter.

3. Patients who have received 4-1BB agonists in the past.

4. Patients who had a major surgery within 4 weeks prior to first administration of IMP.

5. History of progressive multifocal leukoencephalopathy.

6. Active tuberculosis requiring treatment within 3 years prior to the start of treatment or a suspicion of latent tuberculosis by the investigator.

Qualified scientific and medical researchers can request access to anonymized patient-level and study-level clinical trial data.

Access can be requested for all interventional clinical studies:

• used for Marketing Authorization (MA) of medicines and new indications approved after 1 January 2014 in the European Economic Area (EEA) or the United States (US).
• where Servier is the Marketing Authorization Holder (MAH). The date of the first MA of the new medicine (or the new indication) in one of the EEA Member States will be considered for this scope.

In addition, access can be requested for all interventional clinical studies in patients:

• sponsored by Servier
• with a first patient enrolled as of 1 January 2004 onwards
• for New Chemical Entity or New Biological Entity (new pharmaceutical form excluded) for which development has been terminated before any Marketing authorization (MA) approval.

After Marketing Authorization in EEA or US if the study is used for the approval.

Researchers should register on Servier Data Portal and fill in the research proposal form. This form in four parts should be fully documented. The Research Proposal Form will not be reviewed until all mandatory fields are completed.

Through study termination, approximately 3.5 years

All-Cause Mortality is assessed for all randomized participants, regardless of whether the IMP (PRS-344/S095012) was actually taken or not. Serious Adverse Events and Other (Not Including Serious) Adverse Events assessed is based on the treated set which was defined as all participants who received at least one dose of IMP (PRS-344/S095012).

The Sponsor decided to prematurely discontinue recruitment to the CL1-95012-001 study because the overall benefit-risk balance of PRS-344/S095012 was unfavorable. The participants in Phase 1 were allowed to continue the FU until disease progression or any other reason to discontinue study treatment. The Phase 2 dose expansion of the study was not initiated.