An Open-label, Multicenter Study of LY4050784, a Selective SMARCA2/BRM Inhibitor, in Advanced Solid Tumor Malignancies With SMARCA4/BRG1 Alterations (J5M-OX-JOXA)
A Study of LY4050784 in Participants With Advanced or Metastatic Solid Tumors (J5M-OX-JOXA)
Masaki Takeshi
Eli Lilly Japan K.K.
5-1-28, Isogamidori, Chuo-ku, Kobe, Hyogo
+81-120-023-812
LTG_CallCenter@lists.lilly.com
Trial Guide Call Center
Eli Lilly Japan K.K.
5-1-28, Isogamidori, Chuo-ku, Kobe, Hyogo
+81-120-023-812
LTG_CallCenter@lists.lilly.com
Recruiting
Sept. 18, 2024
160
Interventional
non-randomized controlled trial
open(masking not used)
uncontrolled control
parallel assignment
treatment purpose
- Have one of the following locally advanced or metastatic solid tumor malignancy with SMARCA4 (BRG1) alteration:
* Phase 1a dose escalation: Presence of any alteration in SMARCA4 (BRG1)
* Phase 1b expansion: Part A: Non-small Cell Lung Cancer (NSCLC) that is locally advanced and not suitable for definitive locoregional therapy, or metastatic with presence of a known or likely loss of function alteration in SMARCA4 (BRG1) or loss of protein expression.
* Phase 1b expansion: Part B: Any tumor type (other than NSCLC) that has the presence of a known or likely loss of function alteration in SMARCA4 (BRG1) or loss of protein expression.
* Phase 1b expansion: Part C: Non-small Cell Lung Cancer (NSCLC) that is locally advanced and not suitable for definitive locoregional therapy, or metastatic with presence of a known or likely loss of function alteration in SMARCA4 (BRG1) or loss of protein expression.
- Prior Systemic Therapy Criteria:
* Phase 1a dose escalation and Phase 1b (Part B): Participants who received all standard therapies for which the individual was deemed to be an appropriate candidate by the treating Investigator; or the individual is refusing the remaining most appropriate standard of care treatment; or there is no standard therapy available for the disease.
* Phase 1b expansion (Part A): Participants must have received at least one line of therapy for advanced or metastatic disease.
* Phase 1b expansion (Part C): Participants may be treatment naive or have received therapy for advanced or metastatic disease
- Measurability of disease
* Phase 1a dose escalation (excluding backfill): measurable or non-measurable disease as defined by Response Evaluation Criteria in Solid Tumors v1.1 (RECIST v1.1)
* Phase 1a backfill and Phase 1b expansion: Measurable disease required as defined by RECIST v1.1
- Have an Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1
- Participants with known or likely loss of function alteration of SMARCA2 (BRM) or malignancy with known association with SMARCA2 (BRM) alterations
- Prior exposure to SMARCA2 (BRM) inhibitor(s) and/or degrader(s) (prior exposure may be permitted for dose escalation)
- Participants with known or suspected history of untreated or uncontrolled central nervous system (CNS) involvement
- Participants with history of increased risk of prolonged QT or significant arrythmia
- Significant cardiovascular disease
- Participants with active and/or treated for an additional primary malignancy within 2 years prior to enrolment
- Participants who are pregnant, breastfeeding or plan to breastfeed or expecting to conceive or father children during study or within 6 months after the last dose of study intervention
- Participants with history of active autoimmune diseases, history of allogenic stem cell/organ transplant or compromised immune system within past 2 years (Part C only)
Experimental: LY4050784 (Phase 1a - Dose Escalation)
Escalating doses of LY4050784 administered orally.
Interventions:
Drug: LY4050784
Experimental: LY4050784 (Phase 1b - Dose Optimization/Part A)
Comparing 2 or more doses (evaluated during dose escalation) of LY4050784 administered orally.
Interventions:
Drug: LY4050784
Experimental: LY4050784 (Phase 1b - Dose Expansion/Part B)
LY4050784 administered orally.
Interventions:
Drug: LY4050784
Experimental: LY4050784 (Phase 1b - Dose Expansion/Part C) Cohort C1
LY4050784 administered orally in combination in combination with pembrolizumab administered IV in 21-day cycles. Participants may continue to receive treatment until discontinuation criteria are met.
Interventions:
Drug: LY4050784
Drug: Pembrolizumab
Experimental: LY4050784 (Phase 1b - Dose Expansion/Part C) Cohort C2a
LY4050784 administered orally in combination in combination with pembrolizumab, pemetrexed, and platinum (cisplatin or carboplatin) administered IV in 21-day cycles. Participants may continue to receive treatment until discontinuation criteria are met.
Interventions:
Drug: LY4050784
Drug: Pembrolizumab
Drug: Cisplatin
Drug: Carboplatin
Drug: Pemetrexed
Experimental: LY4050784 (Phase 1b - Dose Expansion/Part C) Cohort C2b
LY4050784 administered orally in combination in combination with pembrolizumab, paclitaxel/nab-paclitaxel and carboplatin administered IV in 21-day cycles. Participants may continue to receive treatment until discontinuation criteria are met.
Interventions:
Drug: LY4050784
Drug: Pembrolizumab
Drug: Carboplatin
Drug: Paclitaxel
Drug: Nab paclitaxel
Phase Ia: Number of Participants with One or More Treatment Emergent Adverse Events (TEAEs), Serious Adverse Event(s) (SAEs), and Adverse Event(s) (AEs) [ Time Frame: Up to Approximately 48 Months or 4 Years ]
A summary of TEAEs, SAEs, and AEs regardless of causality, will be reported in the Reported Adverse Events module
Phase 1a: To determine the maximum tolerated dose (MTD)/recommended phase 2 dose (RP2D) of LY4050784 [ Time Frame: Up to Approximately 48 Months or 4 years ]
Number of participants with dose-limiting toxicities (DLTs)
Phase 1b: To assess the antitumor activity of LY4050784 Monotherapy: Overall response rate (ORR) [ Time Frame: Up to Approximately 48 Months or 4 Years]
ORR per investigator assessed Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1)
Phase 1b (Dose optimization only): To confirm the RP2D/optimal dose based on safety and efficacy of LY4050784 [ Time Frame: Up to Approximately 48 Months or 4 Years ]
A summary of TEAEs, SAEs, and AEs regardless of causality, will be reported in the Reported Adverse Events module, ORR and Duration of Response (DOR) per Investigator
Phase 1b (Combination cohorts/Part C): To assess the safety and tolerability of LY4050784 when administered in combination with other anticancer agents [ Time Frame: Up to Approximately 48 Months or 4 Years]
A summary of TEAEs, SAEs, and AEs regardless of causality, will be reported in the Reported Adverse Events module
Eli Lilly Japan K.K.
The Cancer Institute Hospital of JFCR, Institutional Review Board
