A Study of Pinatuzumab Vedotin (DCDT2980S) Combined With Rituximab or Polatuzumab Vedotin (DCDS4501A) Combined With Rituximab or Obinutuzumab in Participants With Relapsed or Refractory B-Cell Non-Hodgkin's Lymphoma (NHL) (ROMULUS)

Genentech

Status and phase: Completed; Phase 2; Phase 1

Conditions: Follicular Lymphoma; Diffuse Large B-Cell Lymphoma

Treatments: Drug: Polatuzumab Vedotin; Drug: Rituximab; Drug: Obinutuzumab; Drug: Pinatuzumab Vedotin

Study type: Interventional

Funder types: Industry

Identifiers

NCT01691898

GO27834

2011-004377-84 (EudraCT Number)

Details and patient eligibility

About

This multicenter, open-label study will evaluate the safety and efficacy of pinatuzumab vedotin (DCDT2980S) or polatuzumab vedotin (DCDS4501A) in combination with rituximab (RTX), as well as of polatuzumab vedotin in combination with obinutuzumab in participants with relapsed or refractory (r/r) follicular lymphoma (FL) and r/r diffuse large B-cell lymphoma (DLBCL).

Enrollment: 231 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2
• Life expectancy of at least 12 weeks
• History of histologically documented r/r Grades 1 to 3a FL, or r/r DLBCL
• Availability of an archival or freshly biopsied tumor tissue sample must be confirmed for study enrollment
• Have a clinical indication for treatment as determined by the investigator
• Must have at least one bi-dimensionally measurable lesion (greater than [>] 1.5 centimeters [cm] in its largest dimension by CT scan or Magnetic Resonance Imaging [MRI])

Exclusion criteria

• Prior use of any monoclonal antibody, radio-immuno-conjugate or antibody drug conjugate within 4 weeks before study start
• Treatment with radiotherapy, chemotherapy, immunotherapy, immunosuppressive therapy, or any investigational anti-cancer agent within 2 weeks prior study start
• Adverse events except for sensory neuropathy from any previous treatments must be resolved or stabilized to Grade less than equal to (</=) 2 prior study start
• Completion of autologous stem cell transplant (SCT) within 100 days prior study start
• Prior allogeneic SCT
• Eligibility for autologous SCT (participants with r/r DLBCL)
• History of severe allergic or anaphylactic reactions to monoclonal antibody therapy (or recombinant antibody-related fusion proteins)
• History of other malignancy that could affect compliance with the protocol or interpretation of results
• Current or past history of central nervous system lymphoma
• Current Grade >1 peripheral neuropathy
• Vaccination with a live vaccine within 28 days prior to treatment

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

231 participants in 6 patient groups

Arm A (FL+DLBCL): RTX+Pinatuzumab,Then RTX+Polatuzumab

Experimental group

Description:

For the first 2 cycles, RTX 375 milligrams per square meter (mg/m\^2) will be given by intravenous (IV) infusion on Day 1 and pinatuzumab vedotin 2.4 milligrams per kilogram (mg/kg) will be administered by IV infusion on Day 2 to Arm A participants (with r/r FL and DLBCL). In the absence of any infusion-related adverse events, RTX and pinatuzumab may be administered on the same day (Day 1) in subsequent cycles beginning with the third cycle. Participants who develop disease progression (PD) will be further treated with RTX 375 mg/m\^2 followed by polatuzumab vedotin 2.4 mg/kg IV infusion on Day 1, beginning no later than 42 days after the last dose of the prior study treatment until a second PD event relative to the tumor assessment, documenting PD on the initial study treatment, clinical deterioration, and/or intolerance to the crossover treatment for up to a maximum of 1 year (17 cycles on an every-21-day schedule).

Treatment:

Drug: Pinatuzumab Vedotin

Drug: Polatuzumab Vedotin

Drug: Rituximab

Arm B (FL+DLBCL): RTX+Polatuzumab,Then RTX+Pinatuzumab

Experimental group

Description:

For the first 2 cycles, RTX 375 mg/m\^2 will be given by IV infusion on Day 1 and polatuzumab vedotin 2.4 mg/kg will be administered by IV infusion on Day 2 to Arm B participants (with r/r FL and DLBCL). In the absence of any infusion-related adverse events, RTX and polatuzumab may be administered on the same day (Day 1) in subsequent cycles beginning with the third cycle. Participants who develop PD would be further treated with RTX 375 mg/m\^2 followed by pinatuzumab vedotin 2.4 mg/kg IV infusion on Day 1, beginning no later than 42 days after the last dose of the prior study treatment until a second PD event relative to the tumor assessment, documenting PD on the initial study treatment, clinical deterioration, and/or intolerance to the crossover treatment for up to a maximum of 1 year (17 cycles on an every-21-day schedule).

Treatment:

Drug: Pinatuzumab Vedotin

Drug: Polatuzumab Vedotin

Drug: Rituximab

Cohort C (FL): RTX + Polatuzumab

Experimental group

Description:

For the first 2 cycles, RTX 375 mg/m\^2 will be given by IV infusion on Day 1 and polatuzumab vedotin 1.8 mg/kg will be administered by IV infusion on Day 2 to Cohort C participants (with r/r FL). In the absence of any infusion-related adverse events, RTX and polatuzumab may be administered on the same day (Day 1) in subsequent cycles beginning with the third cycle for up to a maximum of 1 year (17 cycles on an every-21-day schedule) or significant toxicity, PD, or withdrawal from study.

Treatment:

Drug: Polatuzumab Vedotin

Drug: Rituximab

Cohort E (FL+DLBCL): Obinutuzumab + Polatuzumab

Experimental group

Description:

For the first cycle, obinutuzumab will be given by IV infusion on Days 1, 8, and 15. Polatuzumab vedotin 1.8 mg/kg IV infusion will be given on Day 2 of the first cycle to Cohort E participants (with r/r FL and DLBCL). In the absence of any infusion-related adverse events, obinutuzumab and polatuzumab vedotin may be administered on the same day (Day 1) in subsequent cycles beginning with the second cycle up to a maximum of 8 cycles or significant toxicity, PD, or withdrawal from study.

Treatment:

Drug: Obinutuzumab

Drug: Polatuzumab Vedotin

Cohort G (Expansion, FL): Obinutuzumab + Polatuzumab

Experimental group

Description:

For the first cycle, obinutuzumab will be given by IV infusion on Days 1, 8, and 15. Polatuzumab vedotin 1.8 mg/kg IV infusion will be given on Day 2 of the first cycle to Cohort G participants (with r/r FL). In the absence of any infusion-related adverse events, obinutuzumab and polatuzumab vedotin may be administered on the same day (Day 1) in subsequent cycles beginning with the second cycle of the dose-expansion period to cohort G participants up to a maximum of 8 cycles or significant toxicity, PD, or withdrawal from study.

Treatment:

Drug: Obinutuzumab

Drug: Polatuzumab Vedotin

Cohort H (Expansion, DLBCL): Obinutuzumab + Polatuzumab

Experimental group

Description:

For the first cycle, obinutuzumab will be given by IV infusion on Days 1, 8, and 15. Polatuzumab vedotin 1.8 mg/kg IV infusion will be given on Day 2 of the first cycle to Cohort H participants (with r/r DLBCL). In the absence of any infusion-related adverse events, obinutuzumab and polatuzumab vedotin may be administered on the same day (Day 1) in subsequent cycles beginning with the second cycle of the dose-expansion period to cohort H participants up to a maximum of 8 cycles or significant toxicity, PD, or withdrawal from study.

Treatment:

Drug: Obinutuzumab

Drug: Polatuzumab Vedotin