First-in-Human Study of XMT-1536 in Cancers Likely to Express NaPi2b
- Conditions
- Non Small Cell Lung Cancer MetastaticPlatinum Resistant Ovarian Cancer
- Interventions
- Drug: upifitamab rilsodotin
- Registration Number
- NCT03319628
- Lead Sponsor
- Mersana Therapeutics
- Brief Summary
First-in-human, Phase 1b/2 safety study of the antibody-drug conjugate (ADC) XMT-1536 (upifitamab rilsodotin) administered as an intravenous infusion once every four weeks. Patients with tumor types likely to express NaPi2b were enrolled in dose escalation. Patients with platinum-resistant ovarian cancer and non-small cell lung cancer (adenocarcinoma subtype) were enrolled in the expansion segment of this study. Patients with platinum-resistant, high-grade serous ovarian cancer were enrolled in the UPLIFT segment of this study. In addition to safety assessments, the pharmacokinetics of the drug were assessed along with ADC activity. A QTc sub-study was added for the UPLIFT cohort for a sub-set of sites.
- Detailed Description
This is a multi-center study of XMT-1536 (upifitamab rilsodotin) in patients with tumors likely to express NaPi2b, focusing on patients with platinum-resistant ovarian cancer and non-small cell lung cancer, adenocarcinoma subtype. XMT-1536 (upifitamab rilsodotin) was administered as an intravenous infusion once every four weeks. The study consisted of three segments: dose escalation (DES), dose expansion (EXP), and the pivotal cohort (UPLIFT). The DES segment studied small groups of patients who received increased doses. A Safety Review Committee was established to review the data from each dose level before moving to the next higher dose. The dose escalation cohort has ended and is no longer enrolling patients. Enrollment into the EXP segment consisted of 2 parallel cohorts of patients to confirm the dose that has been identified in DES and estimate the objective response rate in each patient population. The EXP and UPLIFT cohorts are no longer enrolling patients. All adverse events were graded according to the National Cancer Institute (NCI) Common Terminology Criteria version (CTCAE v5.0). Throughout the study, pharmacokinetics were measured using proprietary assays developed by Mersana. Anti-cancer activity were measured via RECIST.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 523
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Dose Expansion - Ovarian Cancer upifitamab rilsodotin Once the maximum tolerated dose or recommended Phase 2 dose is achieved in dose escalation, new groups of patients will receive XMT-1536 (upifitamab rilsodotin) at this fixed-dose. This cohort is closed to enrollment. Dose Escalation upifitamab rilsodotin XMT-1536 (upifitamab rilsodotin) treatment is administered in groups of patients who will receive doses that increase over time. This cohort is closed to enrollment. Dose Expansion - NSCLC adenocarcinoma upifitamab rilsodotin Once the maximum tolerated dose or recommended Phase 2 dose is achieved in dose escalation, new groups of patients will receive XMT-1536 (upifitamab rilsodotin) at this fixed-dose. This cohort is closed to enrollment. Pivotal Cohort (UPLIFT) upifitamab rilsodotin Patients with platinum-resistant ovarian cancer will receive XMT-1536 (upifitamab rilsodotin) to further confirm the efficacy. This cohort is closed to enrollment. QTc Sub-Study upifitamab rilsodotin For sites participating in the sub-study, patients with platinum -resistant ovarian cancer will have the option to enroll in this sub-study to evaluate potential changes in the QTc interval following administration of XMT-1536. This cohort is closed to enrollment.
- Primary Outcome Measures
Name Time Method DES and EXP: Safety and Tolerability First dose up until 30 days after study termination Evaluate incidence and severity of adverse events
DES: Maximum tolerated dose or recommended Phase 2 dose Up to 36 weeks, from the date of first dose until unacceptable side effects or a dose-limiting toxicity is met Evaluate adverse events and concomitant medication use after XMT-1536 (upifitamab rilsodotin) doses
EXP: Anti-neoplastic effects of XMT-1536 (upifitamab rilsodotin) Every 6 weeks for up to 36 weeks Monitor tumor size
UPLIFT: Investigator-assessed objective response rate (ORR) of XMT-1536 (upifitamab rilsodotin) in the ITT-Higher NaPi2b population Every 8 weeks until disease progression or up to 24 months Confirmed ORR is defined as the proportion of patients who have achieved a confirmed complete response (CR) or partial response (PR) per RECIST v1.1 after the initiation of study treatment.
QTc Sub-study: Evaluation of the concentration response analysis of XMT-1536 versus the change in QTcF values 60 minutes prior to first dose, up to 26 hours after Cycle 3 dose "The concentration-QTcf change from baseline deltaQTcF analysis and analysis of central tendency for deltaQTcF
- Secondary Outcome Measures
Name Time Method DES: Anti-neoplastic effects of XMT-1536 (upifitamab rilsodotin) Every 6 weeks for up to 36 weeks Monitor tumor size
UPLIFT: Confirmed Investigator-assessed objective response rate of XMT-1536 (upifitamab rilsodotin) regardless of NaPi2b expression Every 8 weeks until disease progression or up to 24 months Assess the confirmed investigator-assessed objective response rate of XMT-1536 (upifitamab rilsodotin) regardless of NaPi2b expression
UPLIFT: Confirmed objective response rate by independent radiology review (IRR) for patients with high NaPi2b and overall Every 8 weeks until disease progression or up to 24 months Assess the confirmed objective response rate by IRR for patients with high NaPi2b (TPS \>/=75) and overall
DES and EXP: Time of maximum observed concentration of XMT-1536 (upifitamab rilsodotin) Daily for one week after first dose; weekly until 28 days after first dose; immediately before and after and 1 week after all subsequent doses Determine the pharmacokinetics of XMT-1536 (upifitamab rilsodotin)
DES and EXP: Maximum concentration of XMT-1536 (upifitamab rilsodotin) Daily for one week after first dose; weekly until 28 days after first dose; immediately before and after and 1 week after all subsequent doses Determine the pharmacokinetics of XMT-1536 (upifitamab rilsodotin)
DES and EXP: Area under the concentration curve of the last measurable concentration of XMT-1536 (upifitamab rilsodotin) Daily for one week after first dose; weekly until 28 days after first dose; immediately before and after and 1 week after all subsequent doses Determine the pharmacokinetics of XMT-1536 (upifitamab rilsodotin)
DES and EXP: Anti-drug antibody and neutralizing antibody Every 6 weeks for up to 36 weeks Analyze blood for antibodies to XMT-1536 (upifitamab rilsodotin) and neutralizing antibodies
UPLIFT: Duration of objective response (DOR) 4 weeks after first response and every 8 weeks until disease progression or up to 24 months Assess the duration of objective response (DOR) in patients who achieve a response
UPLIFT: Incidence and severity of adverse events First dose up until 60 days after study termination Evaluate incidence and severity of adverse events
QTc Sub-Study: Evaluation of the effect of XMT-1536 on QTcF in patients with platinum-resistant HGSOC by timepoint analysis 60 minutes prior to first dose, up to 26 hours after Cycle 3 dose Con.-QTc evaluation
QTc Sub-Study: Evaluation of the effect of XMT-1536 on the PR-interval (PR), QRS duration (QRS), Heart Rate (HR), and ECG morphology 60 minutes prior to first dose, up to 26 hours after Cycle 3 dose Con.-QTc evaluation
Trial Locations
- Locations (1)
University of Oklahoma
🇺🇸Oklahoma City, Oklahoma, United States