A Study Evaluating the Safety, Pharmacokinetics, and Activity of Cevostamab in Participants With Relapsed or Refractory Multiple Myeloma

NCT04910568 | Active Not Recruiting Phase 1 FDA Drug

• 2 other identifiers: GO425522021-000238-33
• Study Type: interventional
• Target: 126
• Locations: 13 countries
• Sites: 26

Brief Summary

This Phase Ib, multicenter, open-label study will evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of cevostamab monotherapy, cevostamab plus pomalidomide and dexamethasone (Pd) or cevostamab plus daratumumab and dexamethasone (Dd) which will be administered to participants with relapsed or refractory multiple myeloma (R/R MM) via intravenous (IV) infusion.

Conditions

Multiple Myeloma

Outcome Measures

Primary Outcomes (6)

• Recommended Phase II Dose (RP2D)

  Baseline up to approximately 4 years

• Percentage of Participants with Adverse Events

  Baseline up to approximately 4 years

• Percentage of Dose Interruptions

  Baseline up to approximately 4 years

• Percentage of Dose Reductions

  Baseline up to approximately 4 years

• Percentage of Dose Intensity

  Baseline up to approximately 4 years

• Percentage of Treatment Discontinuation

  Baseline up to approximately 4 years

Secondary Outcomes (19)

• Objective Response Rate (ORR)

  Baseline up to approximately 4 years

• Complete Response/Stringent Complete Response (CR/sCR) Rate

  Baseline up to approximately 4 years

• Rate of Very Good Partial Response (VGPR) or Better

  Baseline up to approximately 4 years

• Progression-free Survival (PFS)

  Start of study treatment to first date of disease progression or death from any cause, whichever occurs first (up to approximately 4 years)

• Duration of Response (DOR)

  From first partial response (PR) or better until the first date of disease progression or death from any cause, whichever occurs first (up to approximately 4 years)

Study Arms (3)

Single-Agent Cevostamab (Arm A)

EXPERIMENTAL

Cohort A1S is a safety run-in arm evaluating cevostamab administered in 28-day cycles on a modified weekly schedule. Cohort A1E, an expansion cohort, has been opened and finished enrolling participants. Participants will be treated with single-agent cevostamab administered in 28-day cycles on a modified weekly schedule.

Drug: Cevostamab; Drug: Tocilizumab; Drug: Dexamethasone

Cevostamab plus Pomalidomide and Dexamethasone (Pd) (Arm B)

EXPERIMENTAL

Participants will be treated with cevostamab monotherapy during a 14-day period prior to the start of pomalidomide treatment (cevostamab pre-phase). Cohort B1S is a safety run-in arm evaluating cevostamab and Pd administered in 28-day cycles every 2 weeks (Q2W) followed by every 4 weeks (Q4W) schedule. Additional safety run-in cohort(s) with lower target dose levels of cevostamab may be opened prior to opening the expansion cohorts. Two target dose levels of target dose level 1 (DL1) and lower dose level -1 (DL-1) of cevostamab will be selected for randomization in expansion cohorts. Expansion cohorts will follow the same Q2W/Q4W dosing schedule as Cohort B1S.

Drug: Cevostamab; Drug: Tocilizumab; Drug: Pomalidomide; Drug: Dexamethasone

Cevostamab plus Daratumumab and Dexamethasone (Dd) (Arm C)

EXPERIMENTAL

Cohort C1S is a safety run-in arm evaluating cevostamab and Dd administered in 21 day cycles from Cycle(C)1 - C8 every 3 weeks (Q3W) and 28-day cycles from C9 onwards Q4W. Additional safety run-in cohort(s) with lower target dose levels of cevostamab may be opened prior to opening the expansion cohorts. Two target dose levels of DL1 and DL-1 of cevostamab will be selected for randomization in expansion cohorts. Expansion cohorts will follow the same Q3W/Q4W dosing schedule as Cohort C1S.

Drug: Cevostamab; Drug: Tocilizumab; Drug: Daratumumab; Drug: Dexamethasone

Interventions

Dexamethasone DRUG

Arm A: Dexamethasone will be administered as a premedication. Arms B and C: Dexamethasone will be administered via IV or orally at 20 mg as study investigational medicinal product.

Cevostamab plus Daratumumab and Dexamethasone (Dd) (Arm C); Cevostamab plus Pomalidomide and Dexamethasone (Pd) (Arm B); Single-Agent Cevostamab (Arm A)

Cevostamab DRUG

Cevostamab will be administered intravenously on a 28-day cycle, up to a total of 13 cycles (Arm A), in 28-day cycles Q2W followed by Q4W (Arm B) and in 21 day cycles from C1-C8 Q3W and 28-day cycles from C9 onwards Q4W (Arm C). For Arm A, participants have the option to enter re-treatment after Cycle 13. For Arms B and C, participants can be treated until disease progression or unacceptable toxicity.

Cevostamab plus Daratumumab and Dexamethasone (Dd) (Arm C); Cevostamab plus Pomalidomide and Dexamethasone (Pd) (Arm B); Single-Agent Cevostamab (Arm A)

Tocilizumab DRUG

Tocilizumab will be administered for the treatment of cytokine release syndrome (CRS) when necessary.

Also known as: Actemra/RoActemra

Cevostamab plus Daratumumab and Dexamethasone (Dd) (Arm C); Cevostamab plus Pomalidomide and Dexamethasone (Pd) (Arm B); Single-Agent Cevostamab (Arm A)

Pomalidomide DRUG

Pomalidomide will be administered orally (PO) on a 28-day cycle.

Cevostamab plus Pomalidomide and Dexamethasone (Pd) (Arm B)

Daratumumab DRUG

Daratumumab will be administered subcutaneously (SC) on 21 day (C1-8) and 28-day cycles (C9 onwards).

Cevostamab plus Daratumumab and Dexamethasone (Dd) (Arm C)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
• Life expectancy of at least 12 weeks
• Agreement to provide bone marrow biopsy and aspirate samples
• Resolution of adverse events from prior anti-cancer therapy to Grade \<=1
• Measurable disease
• For women of childbearing potential: agreement to remain abstinent or use contraception, during the treatment period (including treatment interruptions) and for at least 5 months after the last dose of cevostamab and at least 3 months after the last dose of tocilizumab was administered
• For Cohort B1S: Participants with R/R MM who have received at least two prior lines of treatment
• For Cohort B2S and additional cohorts: Participants with R/R MM who have received at least 1 prior line of treatment
• Agreement to comply with all requirements of the pomalidomide pregnancy prevention program
• For women of childbearing potential: agreement to remain abstinent or use two reliable methods of contraception starting at least 4 weeks prior to, during the treatment period, and for at least 4 weeks after the last dose of pomalidomide was administered
• For Cohort C1S: Participants with R/R MM who have received at least two prior lines of treatment
• For Cohort C2S and additional cohorts: Participants with R/R MM who have received at least 1 prior line of therapy
• For women of childbearing potential: agreement to remain abstinent or use contraceptive methods during the treatment period and for at least 102 days after the last dose of daratumumab was administered
• For men: agreement to remain abstinent or use a condom during the treatment period and for at least 102 days after the last dose of daratumumab was administered to avoid exposing the embryo, and agreement to refrain from donating sperm during this same period

You may not qualify if:

• Prior treatment with cevostamab or another agent targeting FcRH5
• Inability to comply with protocol-mandated hospitalization and activities restrictions
• Pregnant or breastfeeding, or intending to become pregnant during the study or within 5 months after the last dose of cevostamab or within 3 months after the last dose of tocilizumab (if applicable).
• Prior use of any monoclonal antibody, radioimmunoconjugate, or antibody-drugconjugate as anti-cancer therapy within 4 weeks before first study treatment, except for the use of non-myeloma therapy
• Prior treatment with systemic immunotherapeutic agents, including, but not limited to, cytokine therapy and anti-CTLA4, anti-PD-1, and antiPD-L1 therapeutic antibodies within 12 weeks or 5 half-lives of the drug, whichever is shorter, before first study treatment
• Prior treatment with chimeric antigen receptor T (CAR T)-cell therapy within 12 weeks before first study treatment
• Treatment with radiotherapy within 4 weeks (systemic radiation) or 14 days (focal radiation) prior to first study treatment
• Treatment with any chemotherapeutic agent or other anti-cancer agent (investigational or otherwise) within 4 weeks or 5 half-lives of the drug, whichever is shorter, prior to first study treatment
• Autologous SCT within 100 days prior to first study treatment
• Prior allogeneic stem cell transplant(ation) (SCT)
• Circulating plasma cell count exceeding 500/micro L or 5% of the peripheral blood white cells
• Prior solid organ transplantation
• History of autoimmune disease
• History of confirmed progressive multifocal leukoencephalopathy
• History of severe allergic or anaphylactic reactions to monoclonal antibody therapy

Sponsors & Collaborators

• Hoffmann-La Roche: collaborator
• Genentech, Inc.: lead

Study Sites (26)

City of Hope

Duarte, California, 91010, United States

Location

City of Hope - Lennar Foundation Cancer Center

Irvine, California, 92618, United States

Location

Colorado Blood Cancer Institute (CBCI) at Presbyterian/ St. Luke's Medical Center

Denver, Colorado, 80218, United States

Location

Karmanos Cancer Institute.

Detroit, Michigan, 48201, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Peter MacCallum Cancer Centre

Melbourne, Victoria, 3002, Australia

Location

The Alfred Hospital

Melbourne, Victoria, 3004, Australia

Location

Cross Cancer Institute

Edmonton, Alberta, T6G 1Z2, Canada

Location

Hamilton Health Sciences

Hamilton, Ontario, L8V 5C2, Canada

Location

University Health Network

Toronto, Ontario, M5G 2M9, Canada

Location

Fakultni Nemocnice Ostrava

Ostrava, 708 52, Czechia

Location

Rigshospitalet

København Ø, 2100, Denmark

Location

Hôpital Saint-Louis

Paris, 75475, France

Location

CHU de Poitiers - La Miletrie

Poitiers, 86021, France

Location

Rambam Medical Center

Haifa, 3109601, Israel

Location

Asst Papa Giovanni Xxiii

Bergamo, Lombardy, 24127, Italy

Location

A.O. Spedali Civili Di Brescia-P.O. Spedali Civili

Brescia, Lombardy, 25123, Italy

Location

Yamagata University Hospital

Yamagata, 990-9585, Japan

Location

Pratia Onkologia Katowice

Katowice, 41-500, Poland

Location

Uniwersytecki Szpital Kliniczny w Poznaniu

Późna, 60-569, Poland

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Samsung Medical Center

Seoul, 06351, South Korea

Location

Hospital Universitari Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital General Universitario Gregorio Marañon

Madrid, 28009, Spain

Location

University College London Hospitals NHS Foundation Trust

London, W1T 7HA, United Kingdom

Location

Royal Marsden Hospital

Sutton, SW3 6JJ, United Kingdom

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

tocilizumab; pomalidomide; daratumumab; Dexamethasone

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Officials

• Clinical Trials

  Genentech, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 27, 2021
• First Posted: June 2, 2021
• Study Start: July 26, 2021
• Primary Completion (Estimated): December 10, 2029
• Study Completion (Estimated): December 10, 2029
• Last Updated: March 19, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

ES (2); IT (2); US (5); AU (2); JP (1); PL (2); CZ (1); IL (1); CA (3); FR (2); KR (2); GB (2); DK (1)