A Phase 1, Open-label, Dose Escalation and Dose Expansion Study for LNCB74, a B7-H4 Targeted Antibody Drug Conjugate, as Monotherapy in Participants With Advanced Solid Tumors
Overview
- Phase
- Phase 1
- Intervention
- LNCB74
- Conditions
- Ovarian Cancer
- Sponsor
- NextCure, Inc.
- Enrollment
- 145
- Locations
- 14
- Primary Endpoint
- Evaluate the safety and tolerability of LNCB74
- Status
- Recruiting
- Last Updated
- 4 months ago
Overview
Brief Summary
This is an open-label, phase 1, dose escalation and dose expansion study to determine safety and tolerability, and to determine the maximum tolerated dose and / or recommended phase 2 dose of LNCB74 in participants with advanced solid tumors.
Investigators
Eligibility Criteria
Inclusion Criteria
- •The participant provides written informed consent
- •≥ 18 years of age on day of signing informed consent.
- •Participant with histologically or cytologically confirmed diagnosis of advanced unresectable and/or metastatic solid tumors
- •A male participant must agree to use contraception and refrain from sperm donation or expecting to father a child
- •A female participant is eligible to participate if she is not pregnant, not breastfeeding, not a woman of childbearing potential
- •Have measurable disease per RECIST 1.1 as assessed by the local site investigator/radiology
- •Able to provide tumor tissue sample.
- •Willing to undergo fresh tumor biopsy at Screening and On-treatment if archival tissue not available
- •Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
- •Life expectancy greater than or equal to 12 weeks as judged by the Investigator.
Exclusion Criteria
- •A WOCBP who has a positive serum pregnancy test (within 72 hours) prior to treatment.
- •Has received prior investigational agents within 4 weeks prior to treatment.
- •Has received anti-cancer chemotherapy (Immunotherapy (non-antibody-based therapy), retinoid therapy, hormonal therapy within 2 weeks prior to treatment.
- •Has received antibody-based anti-cancer therapy within 4 weeks prior to treatment.
- •Has received targeted agents and small molecules within 2 weeks or 5 half-lives, whichever is longer.
- •Has received prior platinum-based chemotherapy and progressed within 4 weeks of initiating therapy (platinum-refractory disease)
- •Has received an ADC with MMAE payload.
- •Has received prior radiotherapy within 2 weeks of start of study treatment for focal radiation or within 4 weeks for wide-field radiotherapy
- •Has received G-CSF or GM-CSF within 7 days prior to start of study treatment.
- •Has received a live or live-attenuated vaccine within 30 days prior to the first dose of study intervention.
Arms & Interventions
Part 1 - Dose Escalation and Backfills
Aim: Doses of LNCB74 will be escalated to determine the maximum tolerated dose (MTD), maximum administered dose (MAD) and/or recommended Phase 2 dose (RP2D). One or more dose levels will be backfilled for safety and additional biomarker data.
Intervention: LNCB74
Part 2 - Dose Expansion / Optimization
Aim: The objectives of the Part 2 Dose Expansion/Optimization are: i) to evaluate safety, tolerability, anti-tumor activity, and pharmacodynamics of LNCB74 in a more homogenous population and ii) characterize the minimally safe and effective dose in a particular tumor type and determine recommended Phase 2 dose(s) (RP2D).
Intervention: LNCB74
Outcomes
Primary Outcomes
Evaluate the safety and tolerability of LNCB74
Time Frame: 24 months
Incidence of AEs, SAEs, AEs meeting protocol defined DLT criteria, AEs leading to discontinuation and death, and laboratory abnormalities per NCI CTCAE v5.0
Define a recommended Phase 2 dose (RP2D) of LNCB74
Time Frame: Up to 24 months
Maximum tolerated dose (MTD), maximum administered dose (MAD) and/or recommended Phase 2 dose (RP2D) of LNCB74
Secondary Outcomes
- Characterize the immunogenicity of LNCB74(24 months)
- Objective Response Rate (ORR)(24 months)
- Duration of Response (DOR)(24 months)
- Disease Control Rate (DCR)(24 months)
- Progression Free Survival Rate (PFSR)(6 months)
- Correlate B7-H4 Expression with Objective Response Rate (ORR)(24 months)
- Correlate B7-H4 Expression with Duration of Response (DOR)(24 months)
- Correlate B7-H4 Expression with Disease Control Rate (DCR)(24 months)
- Correlate B7-H4 Expression with Progression Free Survival (PFS)(24 months)
- Progression Free Survival (PFS)(24 months)
- Time to Peak Drug Concentration (Tmax) of LNCB74(Cycle 1 Days 1, 3, 8 and 15; Cycle 3 Days 1, 3, 8 and 15; Day 1 of Cycles 2, 4, 5, 7 and 9)
- Area Under the Curve (AUC) of LNCB74(Cycle 1 Days 1, 3, 8 and 15; Cycle 3 Days 1, 3, 8 and 15; Day 1 of Cycles 2, 4, 5, 7 and 9)
- Half-life (T1/2) of LNCB74(Cycle 1 Days 1, 3, 8 and 15; Cycle 3 Days 1, 3, 8 and 15; Day 1 of Cycles 2, 4, 5, 7 and 9)
- Maximum Serum Concentration (Cmax) of LNCB74(Cycle 1 Days 1, 3, 8 and 15; Cycle 3 Days 1, 3, 8 and 15; Day 1 of Cycles 2, 4, 5, 7 and 9)