## Protocol Section
### Identification Module
**NCT ID:** NCT06413498

**Acronym:** iMMagine-3

**Brief Title:** A Study Comparing Anitocabtagene Autoleucel to Standard of Care Therapy in Participants With Relapsed/ Refractory Multiple Myeloma

**Official Title:** A Phase 3, Randomized, Open-Label Study to Compare the Efficacy and Safety of Anitocabtagene Autoleucel Versus Standard of Care Therapy in Participants With Relapsed/Refractory Multiple Myeloma

#### Organization Study ID Info
**ID:** KT-US-679-0788
#### Organization
**Class:** INDUSTRY
**Full Name:** Gilead Sciences
#### Secondary ID Infos
**Domain:** European Medicines Agency
**ID:** 2024-511188-26
**Type:** OTHER
### Status Module
#### Completion Date
**Date:** 2031-07

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-14

**Type:** ACTUAL

**Last Update Submit Date:** 2024-05-09

**Overall Status:** NOT_YET_RECRUITING

#### Primary Completion Date
**Date:** 2028-07

**Type:** ESTIMATED

#### Start Date
**Date:** 2024-10

**Type:** ESTIMATED

**Status Verified Date:** 2024-05

#### Study First Post Date
**Date:** 2024-05-14
**Type:** ACTUAL
**Study First Submit Date:** 2024-05-09
**Study First Submit QC Date:** 2024-05-09
### Sponsor Collaborators Module

#### Collaborators

**Class:** INDUSTRY

**Name:** Arcellx, Inc.

#### Lead Sponsor

**Class:** INDUSTRY

**Name:** Kite, A Gilead Company

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** True

**Oversight Has DMC:** False

### Description Module

**Brief Summary:** The goal of this study (iMMagine-3) is to compare the study drug, anitocabtagene autoleucel to standard of care therapy (SOCT) in participants with relapsed/refractory multiple myeloma who have received 1 to 3 prior lines of therapy, including an anti-CD38 monoclonal antibody and an immunomodulatory drug.

The primary objective of this study is to compare the efficacy of anitocabtagene autoleucel versus SOCT in participants with RRMM as measured by progression-free survival (PFS) per blinded independent review committee (IRC).

**Detailed Description:** After completing the treatment period, all participants who will receive anitocabtagene autoleucel, will be followed in the post-treatment follow-up period. Thereafter, participants will transition to a separate long-term follow-up study (KT-US-982-5968) to continue follow-up out to 15 years.

### Conditions Module

**Conditions:**

- Multiple Myeloma

**Keywords:**

- Multiple Myeloma

- CAR-T

- ddBCMA

- BCMA

### Design Module

#### Design Info

**Allocation:** RANDOMIZED

**Intervention Model:** PARALLEL

##### Masking Info

**Masking:** NONE

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 450

**Type:** ESTIMATED

**Phases:**

- PHASE3

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** Participants with RRMM will receive lymphodepletion chemotherapy with cyclophosphamide and fludarabine for 3 days followed by single dose of anitocabtagene autoleucel chimeric antigen receptor positive (CAR+) on Day 1.

**Intervention Names:**

- Drug: Anitocabtagene Autoleucel

- Drug: Cyclophosphamide

- Drug: Fludarabine

**Label:** Anitocabtagene Autoleucel

**Type:** EXPERIMENTAL

#### Arm Group 2

**Description:** Participants will receive the investigator's choice of one of the following therapies:

* pomalidomide, bortezomib, and dexamethasone (PVd) (21-day cycles)
* daratumumab, pomalidomide, and dexamethasone (DPd) (28-day cycles)
* carfilzomib, daratumumab, and dexamethasone (KDd) (28-day cycles)
* carfilzomib and dexamethasone (Kd) (28-day cycles)

**Intervention Names:**

- Drug: Pomalidomide

- Drug: Bortezomib

- Drug: Dexamethasone

- Drug: Daratumumab

- Drug: Carfilzomib

**Label:** Standard of Care Therapy (SOCT)

**Type:** ACTIVE_COMPARATOR

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Anitocabtagene Autoleucel

**Description:** A single infusion of CAR+ transduced autologous T cells

**Name:** Anitocabtagene Autoleucel

**Other Names:**

- CART-ddBCMA

**Type:** DRUG

#### Intervention 2

**Arm Group Labels:**

- Anitocabtagene Autoleucel

**Description:** Administered intravenously

**Name:** Cyclophosphamide

**Type:** DRUG

#### Intervention 3

**Arm Group Labels:**

- Anitocabtagene Autoleucel

**Description:** Administered intravenously

**Name:** Fludarabine

**Type:** DRUG

#### Intervention 4

**Arm Group Labels:**

- Standard of Care Therapy (SOCT)

**Description:** Tablet administered orally

**Name:** Pomalidomide

**Type:** DRUG

#### Intervention 5

**Arm Group Labels:**

- Standard of Care Therapy (SOCT)

**Description:** Administered intravenously or subcutaneously

**Name:** Bortezomib

**Type:** DRUG

#### Intervention 6

**Arm Group Labels:**

- Standard of Care Therapy (SOCT)

**Description:** Tablet administered orally

**Name:** Dexamethasone

**Type:** DRUG

#### Intervention 7

**Arm Group Labels:**

- Standard of Care Therapy (SOCT)

**Description:** Administered intravenously or subcutaneously

**Name:** Daratumumab

**Type:** DRUG

#### Intervention 8

**Arm Group Labels:**

- Standard of Care Therapy (SOCT)

**Description:** Administered intravenously

**Name:** Carfilzomib

**Type:** DRUG

### Outcomes Module

#### Primary Outcomes

**Description:** PFS is defined as the time from randomization to disease progression per International Myeloma Working Group (IMWG) criteria as determined by independent review committee (IRC), or death due to any cause, whichever occurs first.

**Measure:** Progression-Free Survival (PFS)

**Time Frame:** Up to 4 years

#### Secondary Outcomes

**Description:** CR rate is defined as the proportion of participants who achieved a best overall response of CR or sCR per IMWG criteria as determined by IRC.

**Measure:** Complete Response (CR) Rate (CR/ Stringent Complete Response (sCR))

**Time Frame:** Up to 4 years

**Description:** Overall MRD negativity, defined as the proportion of any MRD negativity in participants with bone marrow aspirate (\< 1 in 10\^5 nucleated cells per IMWG criteria using next-generation sequencing (NGS)) at any time after randomization until disease progression, subsequent anti-multiple myeloma (MM) therapy, or death.

**Measure:** Overall Minimal Residual Disease (MRD) Negativity

**Time Frame:** Up to 7 years

**Description:** OS is defined as the time from randomization to death due to any cause.

**Measure:** Overall survival (OS)

**Time Frame:** Up to 7 years

**Description:** ORR is defined as the proportion of participants who achieve a best overall response of at least partial response (PR) or better (sCR, CR, very good partial response (VGPR), or PR) per IMWG criteria.

**Measure:** Overall Response Rate (ORR)

**Time Frame:** Up to 7 years

**Description:** MRD-negative CR/sCR is defined as the proportion of participants achieving MRD-negative CR/sCR until disease progression, subsequent anti-MM therapy, or death.

**Measure:** MRD-negative CR/sCR

**Time Frame:** Up to 7 years

**Description:** MRD-negative VGPR+ is defined as the proportion of participants achieving MRD negativity and sCR/CR/VGPR until disease progression, subsequent anti-MM therapy, or death.

**Measure:** MRD-negative VGPR+

**Time Frame:** Up to 7 years

**Description:** Sustained MRD negativity is defined as the proportion of participants remaining MRD-negative at the 10\^-5 sensitivity threshold for the specified number of months starting from the first MRD-negative assessment date to the last MRD-negative assessment date prior to disease progression, subsequent anti-MM therapy, or death. Duration may include ≥ 12 months. Sustained MRD negativity will be evaluated for overall MRD negativity, MRD-negative CR/sCR, and MRD-negative VGPR+.

**Measure:** Sustained MRD Negativity

**Time Frame:** Up to 7 years

**Description:** DOR is derived only among participants who experience an overall response (sCR, CR, VGPR, or PR) per IMWG criteria and is defined as the time from first overall response to disease progression per IMWG criteria, or death from any cause, whichever occurs first.

**Measure:** Duration of Response (DOR)

**Time Frame:** Up to 7 years

**Description:** Time to progression is defined as the time from randomization to the first documented disease progression per IMWG criteria, or death due to disease progression, whichever occurs first.

**Measure:** Time to Progression

**Time Frame:** Up to 7 years

**Description:** Time to next treatment is defined as the time from randomization to the start of subsequent anti-MM therapy or death from any cause, whichever occurs first.

**Measure:** Time to Next Treatment

**Time Frame:** Up to 7 years

**Measure:** Percentage of Participants Experiencing Treatment-emergent Adverse Events (TEAEs)

**Time Frame:** First dose up to 7 years

**Measure:** Percentage of Participants With Anti-Anitocabtagene Autoleucel CAR Antibodies (Anitocabtagene Autoleucel Arm)

**Time Frame:** Up to 7 years

**Measure:** Percentage of Participants With Presence of Replication-Competent Lentivirus (Anitocabtagene Autoleucel Arm)

**Time Frame:** Up to 7 years

**Description:** The EORTC-QLQ-C30 is a multi-item questionnaire measuring the following content: five (5) multi-item functional scales, three (3) multi-item symptom scales, six (6) single item symptoms scales, one (1) global health status scale, and one (1) global health-related quality of life (HRQoL). Each scale is measured from 0 to 100 after a linear transformation. Higher scores for functioning scales and for the Global Health Status or Global HRQoL scales indicate a higher level of functioning and a better HRQoL respectively, whereas higher scores in symptom scales represent a high level of symptoms.

**Measure:** Change From Baseline in the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Score

**Time Frame:** Up to 7 years

**Description:** The EORTC QLQ-MY20 has 20 items across 4 independent subscales; 2 functional subscales (body image, future perspective), and 2 symptoms scales (disease symptoms, and side effects of treatment) with a recall period of one week. Scores from each subscale are transformed from 0 to 100. For the functional scales, high scores represent improvement. For the symptom scales, higher scores represent worsening.

**Measure:** Change From Baseline in the EORTC - Multiple Myeloma Module (EORTC QLQ-MY20) Score

**Time Frame:** Up to 7 years

**Description:** The EQ-5D-5L questionnaire is a generic measure of health status that provides a simple descriptive profile and a single index value. The EQ-5D-5L comprises 2 components: a questionnaire covering 5 dimensions and a tariff of values based upon direct valuations of health states using a visual analog scale (VAS). The total score for EQ-5D-5L index is presented on a range where higher scores indicate better outcome. A positive change from Baseline indicates improvement.

**Measure:** Change From Baseline in the European Quality of Life 5-Dimension 5-Level Scale (EQ-5D-5L) Score

**Time Frame:** Up to 7 years

**Description:** Healthcare resource utilization will be assessed based on the numbers of hospitalizations, intensive care unit (ICU) inpatient days, and non-ICU inpatient days.

**Measure:** Percentage of Participants Using Healthcare Resources

**Time Frame:** Up to 7 years

### Eligibility Module

**Eligibility Criteria:** Key Inclusion Criteria:

* Documented historical diagnosis of multiple myeloma (MM)
* Received 1 to 3 prior lines of antimyeloma therapy, including an immunomodulatory drug (IMiD) and an anti-cluster of differentiation 38 (CD38) monoclonal antibody (mAb). A minimum of 2 consecutive cycles of an IMiD and an anti-CD38 mAb in any prior line of therapy is required. The IMiD and anti-CD38 mAb do not need to be from the same regimen in the prior line(s) of therapy.
* Documented evidence of progressive disease by IMWG criteria based on the investigator's determination on or within 12 months of the last dose of the last regimen
* Measurable disease at screening per IMWG, defined as any of the following:

  * Serum M-protein level ≥ 0.5 g/dL or urine M-protein level ≥ 200 mg/24 hours; or
  * Light chain MM without measurable disease in the serum or urine: serum free light chain ≥ 10 mg/dL and abnormal serum free light chain ratio
* Only individuals who are candidates to receive at least 1 of the 4 SOCT regimens (PVd, DPd, KDd, or Kd), as determined by the investigator, should be considered for this study
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
* Females of childbearing potential must have a negative serum or urine pregnancy test with a sensitivity of at least 25 mIU/mL (females who have undergone surgical sterilization or who have been postmenopausal for at least 2 years are not considered to be of childbearing potential)

Key Exclusion Criteria:

* Prior B-cell maturation antigen (BCMA)-targeted therapy
* Prior T-cell engager therapy
* Prior CAR therapy or other genetically modified T-cell therapy
* Active or prior history of central nervous system (CNS) or meningeal involvement of MM
* Cardiac atrial or cardiac ventricular MM involvement
* History of or active plasma cell leukemia, Waldenstrom's macroglobulinemia, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes), or amyloidosis
* Active malignancy (other than MM) requiring ongoing treatment for disease control within the last 24 months. Myelodysplastic syndrome (even without ongoing treatment) is not permitted.
* Prior auto-SCT within 12 weeks before randomization
* Prior allogeneic stem cell transplant (allo-SCT)
* High-dose (eg, cumulative \> 70 mg prednisone or equivalent) systemic steroid therapy or any other form of immunosuppressive therapy within 14 days before randomization
* Live vaccine ≤ 4 weeks before randomization
* Contraindication to fludarabine or cyclophosphamide
* History of allergy or hypersensitivity to any study agent or study drug components. Individuals with a history of severe hypersensitivity reaction to dimethyl sulfoxide (DMSO) are excluded.
* Life expectancy \< 12 weeks

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** medinfo@kitepharma.com

**Name:** Medical Information

**Phone:** 844-454-5483(1-844-454-KITE)

**Role:** CONTACT

#### Overall Officials

**Official 1:**

**Affiliation:** Kite, A Gilead Company

**Name:** Kite Study Director

**Role:** STUDY_DIRECTOR

### IPD Sharing Statement Module

**IPD Sharing:** NO

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000009370

- Term: Neoplasms by Histologic Type

- ID: D000009369

- Term: Neoplasms

- ID: D000020141

- Term: Hemostatic Disorders

- ID: D000014652

- Term: Vascular Diseases

- ID: D000002318

- Term: Cardiovascular Diseases

- ID: D000010265

- Term: Paraproteinemias

- ID: D000001796

- Term: Blood Protein Disorders

- ID: D000006402

- Term: Hematologic Diseases

- ID: D000006474

- Term: Hemorrhagic Disorders

- ID: D000008232

- Term: Lymphoproliferative Disorders

- ID: D000007160

- Term: Immunoproliferative Disorders

- ID: D000007154

- Term: Immune System Diseases

### Condition Browse Module - Browse Branches

- Abbrev: BC04

- Name: Neoplasms

- Abbrev: BC14

- Name: Heart and Blood Diseases

- Abbrev: BC15

- Name: Blood and Lymph Conditions

- Abbrev: BC20

- Name: Immune System Diseases

- Abbrev: All

- Name: All Conditions

- Abbrev: Rare

- Name: Rare Diseases

### Condition Browse Module - Browse Leaves

- ID: M12058

- Name: Multiple Myeloma

- Relevance: HIGH

- As Found: Multiple Myeloma

- ID: M27588

- Name: Neoplasms, Plasma Cell

- Relevance: HIGH

- As Found: Multiple Myeloma

- ID: M12315

- Name: Neoplasms by Histologic Type

- Relevance: LOW

- As Found: Unknown

- ID: M21977

- Name: Hemostatic Disorders

- Relevance: LOW

- As Found: Unknown

- ID: M5059

- Name: Blood Coagulation Disorders

- Relevance: LOW

- As Found: Unknown

- ID: M17400

- Name: Vascular Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M13178

- Name: Paraproteinemias

- Relevance: LOW

- As Found: Unknown

- ID: M5077

- Name: Blood Protein Disorders

- Relevance: LOW

- As Found: Unknown

- ID: M9490

- Name: Hematologic Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M9560

- Name: Hemorrhagic Disorders

- Relevance: LOW

- As Found: Unknown

- ID: M11225

- Name: Lymphoproliferative Disorders

- Relevance: LOW

- As Found: Unknown

- ID: M10206

- Name: Immunoproliferative Disorders

- Relevance: LOW

- As Found: Unknown

- ID: M10200

- Name: Immune System Diseases

- Relevance: LOW

- As Found: Unknown

- ID: T3947

- Name: Multiple Myeloma

- Relevance: HIGH

- As Found: Multiple Myeloma

### Condition Browse Module - Meshes

- ID: D000009101

- Term: Multiple Myeloma

- ID: D000054219

- Term: Neoplasms, Plasma Cell

### Intervention Browse Module - Ancestors

- ID: D000007166

- Term: Immunosuppressive Agents

- ID: D000007155

- Term: Immunologic Factors

- ID: D000045505

- Term: Physiological Effects of Drugs

- ID: D000018501

- Term: Antirheumatic Agents

- ID: D000018906

- Term: Antineoplastic Agents, Alkylating

- ID: D000000477

- Term: Alkylating Agents

- ID: D000045504

- Term: Molecular Mechanisms of Pharmacological Action

- ID: D000000970

- Term: Antineoplastic Agents

- ID: D000019653

- Term: Myeloablative Agonists

- ID: D000000893

- Term: Anti-Inflammatory Agents

- ID: D000000932

- Term: Antiemetics

- ID: D000001337

- Term: Autonomic Agents

- ID: D000018373

- Term: Peripheral Nervous System Agents

- ID: D000005765

- Term: Gastrointestinal Agents

- ID: D000005938

- Term: Glucocorticoids

- ID: D000006728

- Term: Hormones

- ID: D000006730

- Term: Hormones, Hormone Substitutes, and Hormone Antagonists

- ID: D000018931

- Term: Antineoplastic Agents, Hormonal

- ID: D000020533

- Term: Angiogenesis Inhibitors

- ID: D000043924

- Term: Angiogenesis Modulating Agents

- ID: D000006133

- Term: Growth Substances

- ID: D000006131

- Term: Growth Inhibitors

### Intervention Browse Module - Browse Branches

- Abbrev: Infl

- Name: Anti-Inflammatory Agents

- Abbrev: ANeo

- Name: Antineoplastic Agents

- Abbrev: AnEm

- Name: Antiemetics

- Abbrev: Gast

- Name: Gastrointestinal Agents

- Abbrev: All

- Name: All Drugs and Chemicals

- Abbrev: ARhu

- Name: Antirheumatic Agents

### Intervention Browse Module - Browse Leaves

- ID: M7102

- Name: Dexamethasone

- Relevance: HIGH

- As Found: Children

- ID: M6727

- Name: Cyclophosphamide

- Relevance: HIGH

- As Found: Cycle

- ID: M283230

- Name: Fludarabine

- Relevance: HIGH

- As Found: Combined

- ID: M225513

- Name: Fludarabine phosphate

- Relevance: LOW

- As Found: Unknown

- ID: M376

- Name: Bortezomib

- Relevance: HIGH

- As Found: 14 days

- ID: M272211

- Name: Daratumumab

- Relevance: HIGH

- As Found: 50%

- ID: M233261

- Name: Pomalidomide

- Relevance: HIGH

- As Found: 1 day

- ID: M235549

- Name: Dexamethasone acetate

- Relevance: LOW

- As Found: Unknown

- ID: M10212

- Name: Immunosuppressive Agents

- Relevance: LOW

- As Found: Unknown

- ID: M10201

- Name: Immunologic Factors

- Relevance: LOW

- As Found: Unknown

- ID: M20604

- Name: Antirheumatic Agents

- Relevance: LOW

- As Found: Unknown

- ID: M20942

- Name: Antineoplastic Agents, Alkylating

- Relevance: LOW

- As Found: Unknown

- ID: M3820

- Name: Alkylating Agents

- Relevance: LOW

- As Found: Unknown

- ID: M4217

- Name: Anti-Inflammatory Agents

- Relevance: LOW

- As Found: Unknown

- ID: M4251

- Name: Antiemetics

- Relevance: LOW

- As Found: Unknown

- ID: M8881

- Name: Gastrointestinal Agents

- Relevance: LOW

- As Found: Unknown

- ID: M9047

- Name: Glucocorticoids

- Relevance: LOW

- As Found: Unknown

- ID: M9789

- Name: Hormones

- Relevance: LOW

- As Found: Unknown

- ID: M9788

- Name: Hormone Antagonists

- Relevance: LOW

- As Found: Unknown

- ID: M20966

- Name: Antineoplastic Agents, Hormonal

- Relevance: LOW

- As Found: Unknown

- ID: M22318

- Name: Angiogenesis Inhibitors

- Relevance: LOW

- As Found: Unknown

- ID: M9231

- Name: Growth Inhibitors

- Relevance: LOW

- As Found: Unknown

### Intervention Browse Module - Meshes

- ID: D000003907

- Term: Dexamethasone

- ID: D000003520

- Term: Cyclophosphamide

- ID: C000024352

- Term: Fludarabine

- ID: D000069286

- Term: Bortezomib

- ID: C000556306

- Term: Daratumumab

- ID: C000467566

- Term: Pomalidomide

### Misc Info Module

- Version Holder: 2024-05-31
