A Phase 1b Study of JNJ-79635322 in Combination With Daratumumab With or Without Lenalidomide or in Combination With Pomalidomide for Multiple Myeloma
概览
- 阶段
- 1 期
- 干预措施
- JNJ-79635322
- 疾病 / 适应症
- Multiple Myeloma
- 发起方
- Janssen Research & Development, LLC
- 入组人数
- 140
- 试验地点
- 27
- 主要终点
- Part 1: Number of Participants with Dose-limiting Toxicity (DLT)
- 状态
- 招募中
- 最后更新
- 19天前
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).
研究者
入排标准
入选标准
- •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 regimen A1: 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 regimen A2: 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
排除标准
- •Any serious underlying medical conditions, such as: a) Evidence of active viral, bacterial, or systemic fungal infection requiring ongoing antiviral, antibacterial, or antifungal treatment. b) Active autoimmune disease requiring systemic immunosuppressive therapy within 6 months before start of study treatment. c) Cardiac conditions (myocardial infarction, unstable angina, or coronary artery bypass graft \<=6 months prior to enrollment; New york heart association stage III or IV congestive heart failure et cetera)
- •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 regimen A 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 less than or equal to (\<=)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
- •The following medical conditions: 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
研究组 & 干预措施
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 a dose of 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
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 a dose of 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
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 (Treatment regimen A1) will receive a dose of 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 regimen A2/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
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 (Treatment regimen A1) will receive a dose of 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 regimen A2/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
Treatment Regimen D and E: JNJ-79635322 + Daratumumab + Lenalidomide Combination
Participants with NDMM will receive a dose of 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
Treatment Regimen D and E: JNJ-79635322 + Daratumumab + Lenalidomide Combination
Participants with NDMM will receive a dose of 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
Treatment Regimen D and E: JNJ-79635322 + Daratumumab + Lenalidomide Combination
Participants with NDMM will receive a dose of 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
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)
- 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)