A Phase 1b Study of JNJ-79635322 in Combination With Daratumumab With or Without Lenalidomide for Multiple Myeloma, Newly Diagnosed AL Amyloidosis, and High-risk Smoldering Multiple Myeloma or in Combination With Pomalidomide for Multiple Myeloma
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 276
- 试验地点
- 16
- 主要终点
- Part 1: Number of Participants with Dose-limiting Toxicity (DLT)
研究概览
简要总结
The primary purpose of this study for Part 1 (Dose Escalation) is to identify the safe effective dose (recommended Phase 2 doses [RP2Ds]) and schedule for JNJ-79635322 treatment regimen in combination with daratumumab with or without lenalidomide or with pomalidomide; and for Part 2 (Dose Expansion) is to further characterize the safety and tolerability of JNJ-79635322 combination treatment regimens at selected RP2D(s).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •for newly diagnosed multiple myeloma (NDMM) and relapsed or refractory multiple myeloma (R/R MM):
- •Have documented initial diagnosis of multiple myeloma according to IMWG diagnostic criteria
- •Meet treatment regimen-specific requirements as follows: Treatment regimen A (JNJ-79635322+daratumumab):Treatment regimens A1 and A3: Have been treated with 1 to 3 prior lines of therapy, including a proteasome inhibitor (PI) and an inhibitor, immunomodulatory drug (IMiD) therapy for the treatment of multiple myeloma (MM); Treatment regimens A2 and A4: Newly diagnosed MM naïve to multiple myeloma (or other related plasma cell neoplasm)-directed treatments; Treatment regimen B (JNJ-79635322+pomalidomide): Have received greater than or equal to (>=) 1 prior line of therapy, including a PI and lenalidomide, and are lenalidomide refractory OR >=2 prior lines of therapy, including a PI and lenalidomide; Treatment Regimens C, D, and E: Newly diagnosed MM naïve to multiple myeloma (or other related plasma cell neoplasm)-directed treatments
- •Have a weight >=40 kilograms
- •Must have an Eastern Cooperative Oncology Group status of 0 or 2
- •Have measurable disease at screening as defined by at least 1 of the following: a) Serum monoclonal protein (M-protein) level >= 0.5 gram per deciliter (g/dL); or b) Urine M-protein level >=200 milligram (mg)/24 hours; or c) Light chain multiple myeloma: Serum immunoglobulin (Ig) free light chain (FLC) >= 10 mg/dL and abnormal serum Ig kappa lambda FLC ratio. d) For participants without measurable disease in the serum, urine, or involved FLC: presence of 1 or more focus of extramedullary disease which meets the following criteria: extramedullary plasmacytoma not contiguous with a bone lesion, at least 1 lesion >=2 centimeter (cm) (at its greatest dimension) diameter on whole body positron emission tomography-computed tomography (or whole-body magnetic resonance imaging approved by sponsor), and not previously radiated
- •Inclusion criteria for newly diagnosed amyloid light chain (ND AL) Amyloidosis
- •Have a histopathological diagnosis of amyloidosis
- •Have an ECOG performance status of 0 to 1
- •Inclusion criteria for High-risk smoldering multiple myeloma (SMM)
- •Have a diagnosis of SMM (per IMWG criteria) for less than or equal to (<=) 5 years with measurable disease at the time of enrollment as defined in the protocol
- •Have an ECOG performance status of 0 to 1
排除标准
- •for NDMM and R/R MM:
- •Prior antitumor therapy as follows, in the specified time frame prior to the first dose of study treatment: a) Targeted therapy, epigenetic therapy, monoclonal antibody (mAb) treatment, or treatment with an investigational drug or an invasive investigational medical device within 21 days or 5 half-lives, whichever is less. b) Gene-modified adoptive cell therapy (example, chimeric antigen receptor [CAR] modified T cells, natural killer cells) within 90 days. c) Prior anti-CD38 directed therapy within 90 days (for treatment regimens A, C, D and E only; within 21 days for treatment regimen B). d) Conventional chemotherapy within 21 days. e) PI therapy within 14 days. f) Immunomodulatory agent therapy within 7 days. g) Radiotherapy within 14 days
- •Stem cell transplantation: a) Allogeneic stem cell transplant within 6 months before the first dose of study treatment. b) Received an autologous stem cell transplant <=12 weeks before the first dose of study treatment
- •Nonhematologic toxicity from prior anticancer therapy that has not resolved to baseline level or to grade <=1 (except alopecia, tissue post-RT fibrosis [any grade] or peripheral neuropathy grade <=3)
- •Prior treatment with CD3-redirecting therapy
- •Exclusion Criteria for ND AL Amyloidosis
- •Previous or current diagnosis of symptomatic multiple myeloma, including the presence of lytic bone disease, plasmacytomas, >=60 percent (%) plasma cells in the bone marrow, or hypercalcemia
- •Macroglossia that impairs swallowing difficulty
- •Prior therapy for AL amyloidosis or multiple myeloma
- •Exclusion Criteria for High-risk SMM
- •Multiple myeloma, requiring treatment
- •Primary systemic AL (immunoglobulin light chain) amyloidosis
- •Exclusion criteria for all participants:
- •Any serious underlying medical conditions, such as: Evidence of active viral, bacterial, or systemic fungal infection requiring ongoing antiviral, antibacterial, or antifungal treatment; active autoimmune disease requiring systemic immunosuppressive therapy within 6 months before start of study treatment; cardiovascular dysfunction; pulmonary compromise requiring supplemental oxygen use to maintain adequate oxygenation; human immunodeficiency (HIV) infection; active hepatitis B or C infection; stroke or seizure within 6 months prior to first dose of study treatment
- •Known or suspected chronic obstructive pulmonary disease (COPD) with a forced expiratory volume in 1 second (FEV1) less than (<) 50 percent (%)
研究组 & 干预措施
Treatment Regimen A and C: JNJ-79635322+Daratumumab
Participants who have received 1-3 prior lines of therapy, including a proteasome inhibitor (PI) and an immunomodulatory drug (IMiD) (Treatment regimen A1 and A3) will receive JNJ-79635322 along with daratumumab to establish the recommended phase 2 doses (RP2D[s]) of the JNJ-79635322 during Part 1 (Dose Escalation) of the study. Based on the study evaluation team (SET) decision, enrollment may proceed in participants with newly diagnosed multiple myeloma (NDMM) (Treatment regimens A2, A4 and C). Dose escalation and de-escalation will be based on SET evaluation. In Part 2 (Dose Expansion) participants will receive a dose of JNJ-79635322 combination treatment regimen(s) at the RP2D(s) determined in Part 1 and in disease subgroup(s) to determine the safety and tolerability of the combination treatment regimens.
干预措施: JNJ-79635322 (Drug)
Treatment Regimen G: JNJ-79635322 + Daratumumab
Participants with high-risk smoldering multiple myeloma (SMM) will receive JNJ-79635322 in treatment regimen G along with daratumumab to establish the RP2D[s] of the JNJ-79635322 during Part 1 (Dose Escalation) of the study. Dose escalation and de-escalation will be based on SET evaluation. In Part 2 (Dose Expansion) participants will receive a dose of JNJ-79635322 and daratumumab at the RP2D(s) determined in Part 1 and in disease subgroup(s) to determine the safety and tolerability of the combination treatment regimens.
干预措施: JNJ-79635322 (Drug)
Treatment Regimen G: JNJ-79635322 + Daratumumab
Participants with high-risk smoldering multiple myeloma (SMM) will receive JNJ-79635322 in treatment regimen G along with daratumumab to establish the RP2D[s] of the JNJ-79635322 during Part 1 (Dose Escalation) of the study. Dose escalation and de-escalation will be based on SET evaluation. In Part 2 (Dose Expansion) participants will receive a dose of JNJ-79635322 and daratumumab at the RP2D(s) determined in Part 1 and in disease subgroup(s) to determine the safety and tolerability of the combination treatment regimens.
干预措施: Daratumumab (Drug)
Treatment Regimen A and C: JNJ-79635322+Daratumumab
Participants who have received 1-3 prior lines of therapy, including a proteasome inhibitor (PI) and an immunomodulatory drug (IMiD) (Treatment regimen A1 and A3) will receive JNJ-79635322 along with daratumumab to establish the recommended phase 2 doses (RP2D[s]) of the JNJ-79635322 during Part 1 (Dose Escalation) of the study. Based on the study evaluation team (SET) decision, enrollment may proceed in participants with newly diagnosed multiple myeloma (NDMM) (Treatment regimens A2, A4 and C). Dose escalation and de-escalation will be based on SET evaluation. In Part 2 (Dose Expansion) participants will receive a dose of JNJ-79635322 combination treatment regimen(s) at the RP2D(s) determined in Part 1 and in disease subgroup(s) to determine the safety and tolerability of the combination treatment regimens.
干预措施: Daratumumab (Drug)
Treatment Regimen D and E: JNJ-79635322 + Daratumumab + Lenalidomide Combination
Participants with NDMM will receive JNJ-79635322 along with daratumumab and lenalidomide to establish the RP2D[s] of the JNJ-79635322 during Part 1 (Dose Escalation) of the study. Dose escalation and de-escalation will be based on SET evaluation. In Part 2 (Dose Expansion) participants will receive a dose of JNJ-79635322 combination treatment regimen(s) at the RP2D(s) determined in Part 1 and in disease subgroup(s) to determine the safety and tolerability of the combination treatment regimens.
干预措施: Daratumumab (Drug)
Treatment Regimen D and E: JNJ-79635322 + Daratumumab + Lenalidomide Combination
Participants with NDMM will receive JNJ-79635322 along with daratumumab and lenalidomide to establish the RP2D[s] of the JNJ-79635322 during Part 1 (Dose Escalation) of the study. Dose escalation and de-escalation will be based on SET evaluation. In Part 2 (Dose Expansion) participants will receive a dose of JNJ-79635322 combination treatment regimen(s) at the RP2D(s) determined in Part 1 and in disease subgroup(s) to determine the safety and tolerability of the combination treatment regimens.
干预措施: Lenalidomide (Drug)
Treatment Regimen B: JNJ-79635322+Pomalidomide
Participants who have received greater than or equal to (>=)1 prior line of therapy, including a PI and lenalidomide, and are lenalidomide refractory or >=2 prior lines of therapy, including a PI and lenalidomide will receive JNJ-79635322 along with pomalidomide to establish the RP2D(s) of the JNJ-79635322 during Part 1 (Dose Escalation) of the study. Dose escalation and de-escalation will be based on SET evaluation. In Part 2 (Dose Expansion) participants will receive a dose of JNJ-79635322 combination treatment regimen(s) at the RP2D(s) determined in Part 1 and in disease subgroup(s) to determine the safety and tolerability of the combination treatment regimens.
干预措施: Pomalidomide (Drug)
Treatment Regimen B: JNJ-79635322+Pomalidomide
Participants who have received greater than or equal to (>=)1 prior line of therapy, including a PI and lenalidomide, and are lenalidomide refractory or >=2 prior lines of therapy, including a PI and lenalidomide will receive JNJ-79635322 along with pomalidomide to establish the RP2D(s) of the JNJ-79635322 during Part 1 (Dose Escalation) of the study. Dose escalation and de-escalation will be based on SET evaluation. In Part 2 (Dose Expansion) participants will receive a dose of JNJ-79635322 combination treatment regimen(s) at the RP2D(s) determined in Part 1 and in disease subgroup(s) to determine the safety and tolerability of the combination treatment regimens.
干预措施: JNJ-79635322 (Drug)
Treatment Regimen D and E: JNJ-79635322 + Daratumumab + Lenalidomide Combination
Participants with NDMM will receive JNJ-79635322 along with daratumumab and lenalidomide to establish the RP2D[s] of the JNJ-79635322 during Part 1 (Dose Escalation) of the study. Dose escalation and de-escalation will be based on SET evaluation. In Part 2 (Dose Expansion) participants will receive a dose of JNJ-79635322 combination treatment regimen(s) at the RP2D(s) determined in Part 1 and in disease subgroup(s) to determine the safety and tolerability of the combination treatment regimens.
干预措施: JNJ-79635322 (Drug)
Treatment Regimen F: JNJ-79635322 + Daratumumab
Participants with newly diagnosed amyloid light chain (ND AL) amyloidosis will receive JNJ-79635322 in treatment regimen F along with daratumumab to establish the RP2D[s] of the JNJ-79635322 during Part 1 (Dose Escalation) of the study. Dose escalation and de-escalation will be based on SET evaluation. In Part 2 (Dose Expansion) participants will receive a dose of JNJ-79635322 and daratumumab at the RP2D(s) determined in Part 1 and in disease subgroup(s) to determine the safety and tolerability of the combination treatment regimens.
干预措施: Daratumumab (Drug)
Treatment Regimen F: JNJ-79635322 + Daratumumab
Participants with newly diagnosed amyloid light chain (ND AL) amyloidosis will receive JNJ-79635322 in treatment regimen F along with daratumumab to establish the RP2D[s] of the JNJ-79635322 during Part 1 (Dose Escalation) of the study. Dose escalation and de-escalation will be based on SET evaluation. In Part 2 (Dose Expansion) participants will receive a dose of JNJ-79635322 and daratumumab at the RP2D(s) determined in Part 1 and in disease subgroup(s) to determine the safety and tolerability of the combination treatment regimens.
干预措施: JNJ-79635322 (Drug)
结局指标
主要结局
Part 1: Number of Participants with Dose-limiting Toxicity (DLT)
时间窗: Up to 28 days
DLTs are specific adverse events and are defined as any of the following: high grade non-hematologic toxicity, or hematologic toxicity.
Number of Participants with Adverse Events (AEs) by Severity
时间窗: Up to 3 Years and 3 months
An AE is any untoward medical occurrence in a clinical study participant that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. Severity will be graded according to the national cancer institute common terminology criteria for adverse events (NCI-CTCAE) version 5.0. Severity scale ranges from grade 1 (mild) to grade 5 (death). Grade 1= mild, Grade 2= moderate, Grade 3= severe, Grade 4= life-threatening and Grade 5= death related to adverse event.
Number of Participants with Clinically Significant Laboratory Abnormalities
时间窗: Up to 3 Years and 3 months
Participants with clinically significant laboratory abnormalities (hematology and chemistry) will be reported.
次要结局
- Percentage of Participants With Overall Response Rate(Up to 3 Years and 3 months)
- Duration of Response (DOR)(Up to 3 Years and 3 months)
- Time to Response (TTR)(Up to 3 Years and 3 months)
- Percentage of Participants With Very Good Partial Response (VGPR) or Better Response Rate(Up to 3 Years and 3 months)
- Percentage of Participants With CR or Better Response Rate(Up to 3 Years and 3 months)
- Percentage of Participants With sCR or Better Response Rate(Up to 3 Years and 3 months)
- Percentage of Participants With Hematologic Response As Defined by International Amyloidosis Consensus Criteria(Up to 3 Years and 3 months)
- DOR as Defined by International Amyloidosis Consensus Criteria(Up to 3 Years and 3 months)
- TTR as Defined by International Amyloidosis Consensus Criteria(Up to 3 Years and 3 months)
- Serum Concentration of JNJ-79635322 and Daratumumab(Up to 3 Years and 3 months)
- Area Under the Serum Concentration Time Curve from Time Zero to Infinity (AUCinf) for JNJ-79635322 and Daratumumab(Up to 3 Years and 3 months)
- Area Under the Serum Concentration Time Curve from Time Zero to the Last Measurable Concentration [AUC(0-t)] for JNJ-79635322 and Daratumumab(Up to 3 Years and 3 months)
- Area Under the Serum Concentration Time Curve During the Dosing Interval (AUCtau) for JNJ-79635322 and Daratumumab(Up to 3 Years and 3 months)
- Maximum Serum Concentration (Cmax) for JNJ-79635322 and Daratumumab(Up to 3 Years and 3 months)
- Half Life (T1/2) for JNJ-79635322 and Daratumumab(Up to 3 Years and 3 months)
- Time to Reach Cmax (Tmax) for JNJ-79635322 and Daratumumab(Up to 3 Years and 3 months)
- Systemic Clearance (CL/F) for JNJ-79635322 and Daratumumab(Up to 3 Years and 3 months)
- Apparent Volume of Distribution at Steady State (Vss/F) for JNJ-79635322 and Daratumumab(Up to 3 Years and 3 months)
- Number of Participants with Presence of Anti-Drug Antibodies to JNJ-79635322 and Daratumumab(Up to 3 Years and 3 months)