A Study to Evaluate Safety and Anti-Tumor Activity of Eciskafusp Alfa (RO7284755) Alone or in Combination With Atezolizumab in Participants With Advanced and/or Metastatic Solid Tumors

Solid Tumors Clinical Trial

Official title:

An Open-Label, Multicenter, Randomized, Dose-Escalation and Extension, Phase IA/IB Study to Evaluate Safety and Anti-Tumor Activity of RO7284755, A PD-1 Targeted IL-2 Variant (IL-2V) Immunocytokine, Alone or in Combination With Atezolizumab in Participants With Advanced and/or Metastatic Solid Tumors

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04303858
• Other study ID #: BP41628
• Secondary ID: 2019-004022-2520
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: May 4, 2020
• Est. completion date: May 27, 2027

Study information

• Verified date: June 2024
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is an entry-into-human study and will assess the effects of eciskafusp alfa (RO7284755) as a single agent and in combination with atezolizumab in adult participants with solid tumors considered responsive to checkpoint inhibition blockade. The maximum duration in the study for each participant will be up to 28 months.

Description:

The study consists of three parts: dose-escalation of eciskafusp alfa as a single agent (Part 1), dose-escalation of eciskafusp alfa in combination with atezolizumab (Part 2), and extension of eciskafusp alfa as a single agent and/or in combination with atezolizumab (Part 3).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 189
• Est. completion date: May 27, 2027
• Est. primary completion date: November 7, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Locally advanced/unresectable or metastatic disease

• No standard of care (SoC) (approved) treatments are available for the participant, or the participant cannot tolerate such treatments

• Measurable disease, as defined by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1)

• Eastern Cooperative Oncology Group Performance Status 0 to 1

• Life expectancy of >=12 weeks

• Consent to provide an archival tumor tissue sample

• Adequate cardiovascular, hematological, coagulative, hepatic and renal function

Exclusion Criteria:

• Rapid disease progression or suspected hyperprogression or threat to vital organs or critical anatomical sites requiring urgent alternative medical intervention

• Untreated central nervous system (CNS) metastases

• Treated asymptomatic CNS metastases

• Spinal cord compression not definitively treated with surgery and/or radiation or previously diagnosed and treated spinal cord compression without evidence that disease has been clinically stable for >= 2 weeks before Cycle1 Day 1 (C1D1)

• Active or history of carcinomatous meningitis/leptomeningeal disease

• Uncontrolled tumor-related pain or symptomatic hypercalcemia

• Concurrent second malignancy

• Evidence of significant, uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of results

• Episode of significant cardiovascular/cerebrovascular acute disease within 28 days before study treatment administration

• Active or uncontrolled infections

• Known HIV infection

• Hepatitis B virus (HBV) or hepatitis C virus infection

• Adverse events related to any prior radiotherapy, chemotherapy, targeted therapy, CPI therapy or surgical procedure must have resolved to Grade <=1, except alopecia Grade 2 peripheral neuropathy, and hypothyroidism and/or hypopituitarism on a stable dosage of hormone replacement therapy

• Participants with bilateral pleural effusion

• Major surgery or significant traumatic injury < 28 days before study treatment administration or anticipation of the need for major surgery during study treatment

• Known allergy or hypersensitivity to any component of the formulations of the IMPs to be administered, including but not limited to hypersensitivity to Chinese hamster ovary cell products or other recombinant or humanized antibodies

• History of severe allergic anaphylactic reactions to chimeric, human or humanized antibodies, or fusion proteins

• Previous treatment with Interleukin-2 (IL-2)/Interleukin-5 (IL-15)-like cytokines. IL-2/IL-15 use as an adjunct treatment component for adoptive cell therapy is permitted. In Part 3, patients who have received adoptive cell therapy such as tumor-infiltrating lymphocytes (TIL) are excluded.

Related Conditions & MeSH terms

• Neoplasms
• Solid Tumors

Intervention

Drug:
• Eciskafusp Alfa
Participants will be administered eciskafusp alfa in different schedules.
• Atezolizumab
Participants will be administered 1200 mg of atezolizumab once every 3 weeks.

Locations

Country	Name	City	State
Belgium	Cliniques Universitaires St-Luc	Bruxelles
Belgium	UZ Leuven Gasthuisberg	Leuven
Canada	Princess Margaret Cancer Center	Toronto	Ontario
Denmark	Herlev Hospital; Afdeling for Kræftbehandling	Herlev
Denmark	Rigshospitalet; Fase 1 Enhed - Onkologi	København Ø
Netherlands	NKI/AvL	Amsterdam
Netherlands	Erasmus MC	Rotterdam
Poland	Uniwersyteckie Centrum Kliniczne; Osrodek Badan Wczesnych Faz	Gda?sk
Poland	Narodowy Instytut Onkologii im. M. Sklodowskiej-Curie; Oddzial Badan Wczesnych Faz	Warszawa
Spain	Hospital Clinic Barcelona; Servicio de oncologia	Barcelona
Spain	Hospital del Mar; Servicio de Oncologia	Barcelona
Spain	Vall d?Hebron Institute of Oncology (VHIO), Barcelona	Barcelona
Spain	Clinica Universidad de Navarra Madrid; Servicio de Oncología	Madrid
Spain	START Madrid-FJD, Hospital Fundacion Jimenez Diaz	Madrid
Spain	Clinica Universitaria de Navarra; Servicio de Oncologia	Pamplona	Navarra

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

Belgium,  Canada,  Denmark,  Netherlands,  Poland,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants with Adverse Events in Part 1 and Part 2	An adverse event (AE) is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as AEs. All AE events will be graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.	From randomization until end of Part 1 and Part 2 (up to approximately 1.5 months)
Primary	Percentage of Participants with Dose-Limiting Toxicities in Part 1 and Part 2	A DLT is defined as a clinically significant AE (classified according to the NCI CTCAE version 5) or significant laboratory abnormality that occur during the DLT assessment periods, during Part 1 and Part 2 only, and is considered by the Investigator to be related to eciskafusp alfa or to the combination of eciskafusp alfa and atezolizumab. In Part 2, expected toxicities that are, in the opinion of the Investigator, entirely attributable to atezolizumab, will not be considered DLTs.	From randomization up to day 14 (Part 1) or day 28 (Part 2)
Primary	Investigator Assessed Objective Response Rate according to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) in Part 3	Objective response rate (ORR) was defined as the percentage of participants with investigator-assessed objective response of complete response (CR) or partial response (PR). PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. CR was defined as disappearance of all target and non-target lesions and normalization of tumor marker levels (as applicable to non-target lesions).	From start of extension phase until disease progression, drug discontinuation, withdrawal or death (up to approximately 26 months)
Primary	Recommended Dose for Extension (RDE) of Eciskafusp Alfa in Parts 1 and 2		From randomization up to day 14 (Part 1) or day 28 (Part 2)
Secondary	Investigator Assessed Objective Response Rate according to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) in Parts 1 and 2	ORR was defined as the percentage of participants with investigator-assessed objective response of complete response (CR) or partial response (PR). PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. CR was defined as disappearance of all target and non-target lesions and normalization of tumor marker levels (as applicable to non-target lesions).	From randomization until end of Part 1 and Part 2 (up to approximately 1.5 months)
Secondary	Percentage of Participants with Adverse Events in Part 3	An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as AEs. All AE events will be graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.	From start of extension phase until disease progression, drug discontinuation, withdrawal or death (up to approximately 26 months)
Secondary	Disease Control Rate in Part 3	The disease control rate was defined as proportion of participants being either responder or in 'stable disease' (SD). To classify a response as SD, measurements will have to be classified as stable (according to RECIST v1.1) at least once at a minimum of 4 weeks after study entry.	From start of extension phase until disease progression, drug discontinuation, withdrawal or death (up to approximately 26 months)
Secondary	Duration of Response in Part 3	Duration of response will be calculated for 'responder' participants (i.e. best [confirmed] overall response of CR or PR) and will be defined as the time from first occurrence of a documented response until the time of documented disease progression or death (death within 30 days from last study treatment) from any cause, whichever occurs first.	From start of extension phase until disease progression, drug discontinuation, withdrawal or death (up to approximately 26 months)
Secondary	Progression-free survival (PFS) in Part 3	Progression-free survival was defined as the time from first dose of study treatment to the first occurrence of documented disease progression (based on RECIST 1.1 Investigator's assessment) or death from any cause, whichever occurs first.	From start of extension phase until disease progression, drug discontinuation, withdrawal or death (up to approximately 26 months)
Secondary	Change from Baseline in Antidrug Antibody (ADA) to Eciskafusp Alfa		Up to 28 months
Secondary	Percentage of Partcipants with ADAs to Eciskafusp Alfa		Up to 28 months
Secondary	Area Under the Curve (AUC) for Eciskafusp Alfa		Predose, C1 Days 1, 2, 3, 5, 8, 9, 10, 12, 15, 16, 17, and 19; C2 Days 1, 2, 8, 9, 10, 12, 15, and 16; C3 Days 1, 2, 3, and 8; C4 Days 1 and 2; C5 Days1, 2, and 8; and days 1 and 2 for any subsequent cycles (Up to 28 months)
Secondary	Minimum Concentration (Cmin) for Eciskafusp Alfa		Predose, C1 Days 1, 2, 3, 5, 8, 9, 10, 12, 15, 16, 17, and 19; C2 Days 1, 2, 8, 9, 10, 12, 15, and 16; C3 Days 1, 2, 3, and 8; C4 Days 1 and 2; C5 Days1, 2, and 8; and days 1 and 2 for any subsequent cycles (Up to 28 months)
Secondary	Maximum Concentration (Cmax) for Eciskafusp Alfa		Predose, C1 Days 1, 2, 3, 5, 8, 9, 10, 12, 15, 16, 17, and 19; C2 Days 1, 2, 8, 9, 10, 12, 15, and 16; C3 Days 1, 2, 3, and 8; C4 Days 1 and 2; C5 Days1, 2, and 8; and days 1 and 2 for any subsequent cycles (Up to 28 months)
Secondary	Clearance (CL) for Eciskafusp Alfa		Predose, C1 Days 1, 2, 3, 5, 8, 9, 10, 12, 15, 16, 17, and 19; C2 Days 1, 2, 8, 9, 10, 12, 15, and 16; C3 Days 1, 2, 3, and 8; C4 Days 1 and 2; C5 Days1, 2, and 8; and days 1 and 2 for any subsequent cycles (Up to 28 months)
Secondary	Volume of Distribution at Steady-State Conditions (Vss) for Eciskafusp Alfa		Predose, C1 Days 1, 2, 3, 5, 8, 9, 10, 12, 15, 16, 17, and 19; C2 Days 1, 2, 8, 9, 10, 12, 15, and 16; C3 Days 1, 2, 3, and 8; C4 Days 1 and 2; C5 Days1, 2, and 8; and days 1 and 2 for any subsequent cycles (Up to 28 months)
Secondary	Percentage of Immune and Tumor Cells with Positive Programmed Cell Death-1 (PD-1) and Programmed Cell Death-Ligand 1 (PD-L1) Expression in the Tumor Microenvironment (TME)		Baseline
Secondary	Percentage of Immune Cells with CD8+ PD1+ and CD8+ PD1+ TCF7+ Expression		Baseline
Secondary	Blood Tumor Mutational Burden	Blood tumor mutational burden is defined as the number of genetic mutations per megabase (1,000,000 bases).	Baseline
Secondary	Change from Baseline in Percentage of Immune Cell Subsets	Immune cells include NK, CD8, and Treg cells	Baseline to End of Treatment (up to approximately 28 months)
Secondary	Change from Baseline in Percentage of Immune Markers	Immune markers include PD-1, PD-L1, sCD25, cytokines, etc...	Baseline to End of Treatment (up to approximately 28 months)