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Rovalpituzumab Tesirine (SC16LD6.5) in Recurrent Small Cell Lung Cancer

Phase I/II Open Label Dose Escalation Study of the Safety, Pharmacokinetics, and Preliminary Efficacy of SC16LD6.5 as a Single Agent in Patients With Recurrent Small Cell Lung Cancer

Status
Completed
Phases
Phase 1Phase 2
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT01901653
Enrollment
82
Registered
2013-07-17
Start date
2013-07-31
Completion date
2016-11-28
Last updated
2018-08-09

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Recurrent Small Cell Lung Cancer

Keywords

Small cell lung cancer

Brief summary

The purpose of this study is to assess the safety and tolerability of rovalpituzumab tesirine (SC16LD6.5) at different dose levels in patients with small cell lung cancer whose cancer has progressed or recurred following standard chemotherapy. Once a safe and tolerable dose is determined, the anti-cancer activity of SC16LD6.5 will be assessed by measuring the extent of tumor shrinkage. SC16LD6.5 is an antibody-drug conjugate (ADC). The antibody (SC16) targets a protein that appears to be expressed on the surface of most small cell lung cancers that have been assessed using an immunohistochemical assay. The drug, D6.5, is a very potent form of chemotherapy, specifically a DNA-damaging agent, that is cell cycle independent. ADC's theoretically provide more precise delivery of chemotherapy to cancer cells, possibly improving effectiveness relative to toxicities.

Interventions

DRUGRovalpituzumab tesirine (SC16LD6.5)

Sponsors

Stemcentrx
Lead SponsorINDUSTRY

Study design

Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE

Eligibility

Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No

Inclusion criteria

1. Provision of informed consent 2. Male or female ≥18 years of age 3. Histologic or cytologic confirmed diagnosis of small cell lung cancer, either limited or extensive disease at initial presentation is allowed 4. Evidence of progressive disease during or following 1 or 2 prior chemotherapy regimens * At least 1 prior regimen must have contained a platinum salt * 'Adjuvant therapy' will constitute a prior treatment regimen * No more than 2 prior regimens are allowed 5. Measurable disease (only for the phase II portion) 6. Eastern Cooperative Oncology Group (ECOG) Performance status 0-1 7. A minimum life expectancy of 12 weeks 8. Adequate bone marrow, hepatic and renal function as evidenced by: * Absolute neutrophil count (ANC) ≥ 1.5 x 109/L * Platelet count ≥ 100 x 109/L * Hemoglobin ≥ 9.0 g/dL * Serum bilirubin \< 1.5 x ULN * Aspartate aminotransferase (AST)/Alanine transferase (ALT) (SGOT/SGPT) \< 2.5 x ULN for the reference laboratory or \< 5 x ULN in the presence of liver metastases * Serum creatinine \< 1.5 x ULN 9. No 'active' CNS metastases. Prior CNS metastases are allowed, provided adequate palliative therapy has been administered and CNS disease control has been established prior to study entry. • A brain MRI scan, ≤ 28 days from day 1, is required 10. Female patients who are not of child-bearing potential, and female patients of child-bearing potential who agree to use adequate contraceptive measures and who have a negative serum pregnancy test within 1 week prior to initial study treatment. (See Appendix B) 11. Male patients willing to use adequate contraceptive. (See Appendix B) 12. At least 21 days must have elapsed prior to day 1 cycle 1, from chemotherapy, radiotherapy, immunotherapy or following major surgery and any surgical incision should be completely healed. At least 14 days must have elapsed prior to Day 1 Cycle 1 for limited palliative radiotherapy, defined as a course of therapy encompassing \< 25% total bone marrow volume and not exceeding 30 Gy. 13. At least 14 days must have elapsed for chemotherapy regimens, biologic, and targeted therapy given continuously or on a weekly basis with limited potential for delayed toxicity.

Exclusion criteria

1. Patients who are pregnant or breastfeeding. 2. Active involvement of the Central Nervous System (CNS). 3. Uncontrolled infection or systemic disease. 4. Clinically significant cardiac disease not well controlled with medication (e.g., congestive heart failure, symptomatic coronary artery disease e.g. angina, and cardiac arrhythmias) or myocardial infarction within the last 12 months. 5. Chemotherapy regimens within the last 21 days (or within 6 weeks for prior nitrosourea or mitomycin C). Chemotherapy regimens, biologic, and targeted therapy given continuously or on a weekly basis with limited potential for delayed toxicity within the last 14 days. 6. No concurrent systemic chemotherapy or anticancer biologic therapy is allowed. Note: Patients on hormonal treatment for breast cancer or prostate cancer may continue on treatment and enter into study. 7. Known hypersensitivity to any components of SC16LD6.5 study drug product. 8. Patients with known human immunodeficiency virus (HIV) or Hepatitis B or C (active, previously treated or both), a history of solid organ or bone marrow transplantation would generally be considered to have met

Design outcomes

Primary

MeasureTime frameDescription
Maximum Tolerated Dose (MTD) of Rovalpituzumab TesirineThe DLT period was defined as either 21 or 42 days following the first dose of Rovalpituzumab tesirine during dose escalation (Phase 1a), depending on Cycle length.MTD was determined by testing increasing doses from 0.05 mg/kg up to 0.8 mg/kg on Day 1 of every 21-day or 42-day cycle, Phase 1a cohorts 1 to 8. MTD will be defined as the dose level immediately below the dose level at which ≥ 2 of the first 3 subjects per cohort (or ≥ 2 of 6 subjects) during the first cycle experience a study drug related dose limiting toxicity (DLT).

Secondary

MeasureTime frameDescription
Duration of Response (DOR)From first dose of Rovalpituzumab tesirine to last event timepoint, up through study completion (on average approximately 4 months, but up to 6.51 months).Duration of response (DOR) was defined as the number of months from the initial CR or PR to the time of disease progression or death, whichever occurred first. Outcome is based on data reported by Investigator (INV); available and evaluable radiographic scans were collected retrospectively for review by an Independent Review Committee (IRC).
Clinical Benefit Rate (CBR)From first dose of Rovalpituzumab tesirine to last event timepoint, up through study completion (on avergae approximately 4 months).Clinical Benefit is defined as a subject with best Overall Response of Complete Response (CR) or Partial Response (PR) or Stable Disease (SD) prior to receiving any subsequent anticancer therapy; as defined by RECIST version 1.1. CBR is defined as the proportion of subjects with Clinical Benefit based on assessment of overall response. CBR will be presented as a number and percentage with 95% confidence bounds. Any subjects not exhibiting a response (CR or PR or SD) are considered non-responders. Outcome is based on data reported by Investigator (INV); available and evaluable radiographic scans were collected retrospectively for review by an Independent Review Committee (IRC).
Progression-free Survival (PFS)From first dose of rovalpituzumab tesirine to last event timepoint, up through study completion (approximately 4 months on average, but up to 14.46 months).Progression-free survival (PFS) was defined as the number of months from the first day of study drug administration to disease recurrence or progression, or death on study. Outcome is based on data reported by Investigator (INV); available and evaluable radiographic scans were collected retrospectively for review by an Independent Review Committee (IRC).
Objective Response Rate (ORR)From first dose of rovalpituzumab tesirine to last event, up through study completion (on average approximately 4 months).Overall response was assessed at each visit post-baseline based on a subject's lesion measurements or assessments (complete response \[CR\], partial response \[PR\], stable disease \[SD\], progressive disease \[PD\], or not evaluable as defined by RECIST v1.1, plus an additional category of early death). The best overall response was then determined. A subject was defined as having an objective response if they had a best overall response of CR or PR prior to receiving any subsequent anticancer therapy; confirmed response is confirmation of CR or PR at least 4 weeks from the initial determination per RECIST v1.1. Subjects with a post-baseline assessment were included in the calculations for objective response rate (ORR). Outcome is based on data reported by Investigator (INV); available and evaluable radiographic scans were collected retrospectively for review by an Independent Review Committee (IRC).
Maximum Serum Concentration (Cmax) of Rovalpituzumab Tesirine Antibody Drug Conjugate (ADC)From Day 1 of first dose to End of Dose CycleThe maximum serum concentration (Cmax; measured in μg/mL) is the highest concentration that a drug achieves in the blood after administration in a dosing cycle.
Area Under the Serum Concentration-time Curve (AUC) of Rovalpituzumab Tesirine ADCFrom Day 1 of first dose to End of Dose CycleThe area under the serum concentration-time curve (AUC; measured in μg•d/mL) is a method of measurement to determine the total exposure of a drug in blood serum.
Overall SurvivalFrom first dose of Rovalpituzumab tesirine to last event, up through study completion (on average approximately 5-7 months, but up to 14.6 months).Overall survival (OS) was defined as the time from the first day of study treatment to death. Subjects who were alive were censored at the date of last known alive.

Countries

United States

Participant flow

Participants by arm

ArmCount
Phase 1a: Cohort 1 (SCLC)
SCLC Subjects: Rovalpituzumab tesirine 0.05 mg/kg on Day 1 of every 21-day cycle
3
Phase 1a: Cohort 2 (SCLC)
SCLC Subjects: Rovalpituzumab tesirine 0.1 mg/kg on Day 1 of every 21-day cycle
1
Phase 1a: Cohort 3 (SCLC)
SCLC Subjects: Rovalpituzumab tesirine 0.2 mg/kg on Day 1 of every 21-day cycle
11
Phase 1a: Cohort 4 (SCLC)
SCLC Subjects: Rovalpituzumab tesirine 0.4 mg/kg on Day 1 of every 21-day cycle
3
Phase 1a: Cohort 5 (SCLC)
SCLC Subjects: Rovalpituzumab tesirine 0.8 mg/kg on Day 1 of every 21-day cycle
2
Phase 1a: Cohort 6 (SCLC)
SCLC Subjects: Rovalpituzumab tesirine 0.4 mg/kg on Day 1 of every 42-day cycle
3
Phase 1a: Cohort 7 (SCLC)
SCLC Subjects: Rovalpituzumab tesirine 0.3 mg/kg on Day 1 of every 42-day cycle
7
Phase 1a: Cohort 8 (SCLC)
SCLC Subjects: Rovalpituzumab tesirine 0.2 mg/kg on Day 1 of every 21-day cycle
10
Phase 1a: Cohort 8 (LCNEC)
LCNEC Subjects: Rovalpituzumab tesirine 0.2 mg/kg on Day 1 of every 21-day cycle
1
Phase 1b: Retreatment (SCLC)
SCLC Subjects: Rovalpituzumab tesirine 0.3 mg/kg on Day 1 of every 42-day cycle for 2 cycles; if eligible, retreatment with rovalpituzumab tesirine 0.3 mg/kg on Day 1 of every 42-day cycle for 2 cycles. Ongoing subjects from Phase 1a who received an initial dose of 0.2 mg/kg on Day 1 of each 21-day cycle for 3 cycles, and if eligible, retreatment with rovalpituzumab tesirine 0.3 mg/kg on Day 1 of every 42-day cycle for 2 cycles.
18
Phase 1b: Retreatment (LCNEC)
LCNEC Subjects: Rovalpituzumab tesirine 0.3 mg/kg on Day 1 of every 42-day cycle for 2 cycles; if eligible, retreatment with rovalpituzumab tesirine 0.3 mg/kg on Day 1 of every 42-day cycle for 2 cycles. Ongoing subjects from Phase 1a who received an initial dose of 0.2 mg/kg on Day 1 of each 21-day cycle for 3 cycles, and if eligible, retreatment with rovalpituzumab tesirine 0.3 mg/kg on Day 1 of every 42-day cycle for 2 cycles.
2
Phase 1b: Maintenance (SCLC)
SCLC Subjects: Rovalpituzumab tesirine 0.3 mg/kg on Day 1 of every 42-day cycle for 2 cycles; followed by maintenance with rovalpituzumab tesirine 0.1 mg/kg on Day 1 of every 42-day cycle
16
Phase 1b: Maintenance (LCNEC)
LCNEC Subjects: Rovalpituzumab tesirine 0.3 mg/kg on Day 1 of every 42-day cycle for 2 cycles; followed by maintenance with rovalpituzumab tesirine 0.1 mg/kg on Day 1 of every 42-day cycle
5
Total82

Withdrawals & dropouts

PeriodReasonFG000FG001FG002FG003FG004FG005FG006FG007FG008FG009FG010FG011FG012
Overall StudyAlive at Study Termination by Sponsor0010000002011
Overall StudyDeath218322691162154
Overall StudyLost to Follow-up1020010100000
Overall StudyWithdrawal by Subject0000001000000

Baseline characteristics

CharacteristicPhase 1a: Cohort 3 (SCLC)Phase 1a: Cohort 1 (SCLC)Phase 1b: Maintenance (LCNEC)TotalPhase 1a: Cohort 4 (SCLC)Phase 1a: Cohort 5 (SCLC)Phase 1a: Cohort 6 (SCLC)Phase 1a: Cohort 7 (SCLC)Phase 1a: Cohort 8 (SCLC)Phase 1a: Cohort 8 (LCNEC)Phase 1b: Retreatment (SCLC)Phase 1b: Retreatment (LCNEC)Phase 1b: Maintenance (SCLC)Phase 1a: Cohort 2 (SCLC)
Age, Categorical
<=18 years
0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants
Age, Categorical
>=65 years
5 Participants0 Participants3 Participants31 Participants1 Participants0 Participants2 Participants2 Participants3 Participants0 Participants7 Participants1 Participants7 Participants0 Participants
Age, Categorical
Between 18 and 65 years
6 Participants3 Participants2 Participants51 Participants2 Participants2 Participants1 Participants5 Participants7 Participants1 Participants11 Participants1 Participants9 Participants1 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status
0
4 Participants2 Participants1 Participants23 Participants2 Participants1 Participants1 Participants0 Participants3 Participants0 Participants3 Participants1 Participants5 Participants0 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status
1
7 Participants1 Participants3 Participants55 Participants1 Participants1 Participants2 Participants6 Participants7 Participants1 Participants13 Participants1 Participants11 Participants1 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status
2
0 Participants0 Participants1 Participants4 Participants0 Participants0 Participants0 Participants1 Participants0 Participants0 Participants2 Participants0 Participants0 Participants0 Participants
Ethnicity (NIH/OMB)
Hispanic or Latino
0 Participants0 Participants0 Participants1 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants1 Participants0 Participants0 Participants0 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
10 Participants3 Participants4 Participants75 Participants3 Participants2 Participants3 Participants7 Participants10 Participants1 Participants14 Participants2 Participants15 Participants1 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
1 Participants0 Participants1 Participants6 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants3 Participants0 Participants1 Participants0 Participants
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants
Race (NIH/OMB)
Asian
0 Participants0 Participants1 Participants3 Participants0 Participants0 Participants1 Participants1 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants
Race (NIH/OMB)
Black or African American
0 Participants0 Participants0 Participants2 Participants1 Participants0 Participants0 Participants1 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants
Race (NIH/OMB)
More than one race
0 Participants0 Participants0 Participants1 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants1 Participants0 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants
Race (NIH/OMB)
Unknown or Not Reported
1 Participants0 Participants1 Participants5 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants3 Participants0 Participants0 Participants0 Participants
Race (NIH/OMB)
White
10 Participants3 Participants3 Participants71 Participants2 Participants2 Participants2 Participants5 Participants10 Participants1 Participants15 Participants2 Participants15 Participants1 Participants
Region of Enrollment
United States
11 participants3 participants5 participants82 participants3 participants2 participants3 participants7 participants10 participants1 participants18 participants2 participants16 participants1 participants
Sex: Female, Male
Female
4 Participants2 Participants2 Participants34 Participants2 Participants1 Participants1 Participants2 Participants4 Participants0 Participants11 Participants0 Participants4 Participants1 Participants
Sex: Female, Male
Male
7 Participants1 Participants3 Participants48 Participants1 Participants1 Participants2 Participants5 Participants6 Participants1 Participants7 Participants2 Participants12 Participants0 Participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
EG002
affected / at risk
EG003
affected / at risk
EG004
affected / at risk
EG005
affected / at risk
EG006
affected / at risk
EG007
affected / at risk
EG008
affected / at risk
EG009
affected / at risk
EG010
affected / at risk
EG011
affected / at risk
EG012
affected / at risk
deaths
Total, all-cause mortality
— / —— / —— / —— / —— / —— / —— / —— / —— / —— / —— / —— / —— / —
other
Total, other adverse events
3 / 31 / 111 / 113 / 32 / 23 / 37 / 710 / 101 / 118 / 182 / 215 / 165 / 5
serious
Total, serious adverse events
0 / 30 / 13 / 113 / 32 / 22 / 31 / 74 / 101 / 17 / 181 / 25 / 164 / 5

Outcome results

Primary

Maximum Tolerated Dose (MTD) of Rovalpituzumab Tesirine

MTD was determined by testing increasing doses from 0.05 mg/kg up to 0.8 mg/kg on Day 1 of every 21-day or 42-day cycle, Phase 1a cohorts 1 to 8. MTD will be defined as the dose level immediately below the dose level at which ≥ 2 of the first 3 subjects per cohort (or ≥ 2 of 6 subjects) during the first cycle experience a study drug related dose limiting toxicity (DLT).

Time frame: The DLT period was defined as either 21 or 42 days following the first dose of Rovalpituzumab tesirine during dose escalation (Phase 1a), depending on Cycle length.

Population: All subjects from Phase 1a Dose Escalation: Cohort 1 to 8 who received at least 1 dose of study drug.

ArmMeasureValue (NUMBER)
Rovalpituzumab TesirineMaximum Tolerated Dose (MTD) of Rovalpituzumab Tesirine0.4 mg/kg
Secondary

Area Under the Serum Concentration-time Curve (AUC) of Rovalpituzumab Tesirine ADC

The area under the serum concentration-time curve (AUC; measured in μg•d/mL) is a method of measurement to determine the total exposure of a drug in blood serum.

Time frame: From Day 1 of first dose to End of Dose Cycle

Population: All subjects who received at least 1 dose of study drug, with evaluable data at each given timepoint. For Phase 1b, pharmacokinetic (PK) sampling was sparse; therefore, pharmacokinetic parameters were not estimated.

ArmMeasureValue (GEOMETRIC_MEAN)Dispersion
Rovalpituzumab TesirineArea Under the Serum Concentration-time Curve (AUC) of Rovalpituzumab Tesirine ADC12.3 μg•d/mLGeometric Coefficient of Variation 22
LCNEC SubjectsArea Under the Serum Concentration-time Curve (AUC) of Rovalpituzumab Tesirine ADC26.3 μg•d/mL—
Phase 1a: Cohort 3Area Under the Serum Concentration-time Curve (AUC) of Rovalpituzumab Tesirine ADC45.6 μg•d/mLGeometric Coefficient of Variation 32
Phase 1a: Cohort 4Area Under the Serum Concentration-time Curve (AUC) of Rovalpituzumab Tesirine ADC97.3 μg•d/mLGeometric Coefficient of Variation 21
Phase 1a: Cohort 5Area Under the Serum Concentration-time Curve (AUC) of Rovalpituzumab Tesirine ADC142 μg•d/mLGeometric Coefficient of Variation 18
Phase 1a: Cohort 6Area Under the Serum Concentration-time Curve (AUC) of Rovalpituzumab Tesirine ADC107 μg•d/mLGeometric Coefficient of Variation 28
Phase 1a: Cohort 7Area Under the Serum Concentration-time Curve (AUC) of Rovalpituzumab Tesirine ADC64.8 μg•d/mLGeometric Coefficient of Variation 36
Phase 1a: Cohort 8Area Under the Serum Concentration-time Curve (AUC) of Rovalpituzumab Tesirine ADC45.0 μg•d/mLGeometric Coefficient of Variation 34
Secondary

Clinical Benefit Rate (CBR)

Clinical Benefit is defined as a subject with best Overall Response of Complete Response (CR) or Partial Response (PR) or Stable Disease (SD) prior to receiving any subsequent anticancer therapy; as defined by RECIST version 1.1. CBR is defined as the proportion of subjects with Clinical Benefit based on assessment of overall response. CBR will be presented as a number and percentage with 95% confidence bounds. Any subjects not exhibiting a response (CR or PR or SD) are considered non-responders. Outcome is based on data reported by Investigator (INV); available and evaluable radiographic scans were collected retrospectively for review by an Independent Review Committee (IRC).

Time frame: From first dose of Rovalpituzumab tesirine to last event timepoint, up through study completion (on avergae approximately 4 months).

Population: Subjects with at least one post-dose assessment.

ArmMeasureGroupValue (NUMBER)
Rovalpituzumab TesirineClinical Benefit Rate (CBR)CBR unconfirmed by INV73 percentage of subjects
Rovalpituzumab TesirineClinical Benefit Rate (CBR)CBR confirmed by INV58 percentage of subjects
Rovalpituzumab TesirineClinical Benefit Rate (CBR)CBR unconfirmed by IRC75 percentage of subjects
Rovalpituzumab TesirineClinical Benefit Rate (CBR)CBR confirmed by IRC56 percentage of subjects
LCNEC SubjectsClinical Benefit Rate (CBR)CBR confirmed by IRC75 percentage of subjects
LCNEC SubjectsClinical Benefit Rate (CBR)CBR unconfirmed by INV88 percentage of subjects
LCNEC SubjectsClinical Benefit Rate (CBR)CBR unconfirmed by IRC75 percentage of subjects
LCNEC SubjectsClinical Benefit Rate (CBR)CBR confirmed by INV75 percentage of subjects
Secondary

Duration of Response (DOR)

Duration of response (DOR) was defined as the number of months from the initial CR or PR to the time of disease progression or death, whichever occurred first. Outcome is based on data reported by Investigator (INV); available and evaluable radiographic scans were collected retrospectively for review by an Independent Review Committee (IRC).

Time frame: From first dose of Rovalpituzumab tesirine to last event timepoint, up through study completion (on average approximately 4 months, but up to 6.51 months).

Population: Subjects with at least one post-dose assessment. No LCNEC subjects achieved CR or PR, therefore DOR was not analyzed.

ArmMeasureGroupValue (MEDIAN)
Rovalpituzumab TesirineDuration of Response (DOR)DOR by IRC1.71 months
Rovalpituzumab TesirineDuration of Response (DOR)DOR by INV2.89 months
Secondary

Maximum Serum Concentration (Cmax) of Rovalpituzumab Tesirine Antibody Drug Conjugate (ADC)

The maximum serum concentration (Cmax; measured in μg/mL) is the highest concentration that a drug achieves in the blood after administration in a dosing cycle.

Time frame: From Day 1 of first dose to End of Dose Cycle

Population: All subjects who received at least 1 dose of study drug, with evaluable data at each given timepoint. For Phase 1b, pharmacokinetic (PK) sampling was sparse; therefore, pharmacokinetic parameters were not estimated.

ArmMeasureValue (GEOMETRIC_MEAN)Dispersion
Rovalpituzumab TesirineMaximum Serum Concentration (Cmax) of Rovalpituzumab Tesirine Antibody Drug Conjugate (ADC)1.27 μg/mLGeometric Coefficient of Variation 13
LCNEC SubjectsMaximum Serum Concentration (Cmax) of Rovalpituzumab Tesirine Antibody Drug Conjugate (ADC)2.42 μg/mL—
Phase 1a: Cohort 3Maximum Serum Concentration (Cmax) of Rovalpituzumab Tesirine Antibody Drug Conjugate (ADC)5.08 μg/mLGeometric Coefficient of Variation 21
Phase 1a: Cohort 4Maximum Serum Concentration (Cmax) of Rovalpituzumab Tesirine Antibody Drug Conjugate (ADC)8.81 μg/mLGeometric Coefficient of Variation 7
Phase 1a: Cohort 5Maximum Serum Concentration (Cmax) of Rovalpituzumab Tesirine Antibody Drug Conjugate (ADC)18.8 μg/mLGeometric Coefficient of Variation 27
Phase 1a: Cohort 6Maximum Serum Concentration (Cmax) of Rovalpituzumab Tesirine Antibody Drug Conjugate (ADC)11.4 μg/mLGeometric Coefficient of Variation 27
Phase 1a: Cohort 7Maximum Serum Concentration (Cmax) of Rovalpituzumab Tesirine Antibody Drug Conjugate (ADC)7.67 μg/mLGeometric Coefficient of Variation 21
Phase 1a: Cohort 8Maximum Serum Concentration (Cmax) of Rovalpituzumab Tesirine Antibody Drug Conjugate (ADC)5.36 μg/mLGeometric Coefficient of Variation 26
Secondary

Objective Response Rate (ORR)

Overall response was assessed at each visit post-baseline based on a subject's lesion measurements or assessments (complete response \[CR\], partial response \[PR\], stable disease \[SD\], progressive disease \[PD\], or not evaluable as defined by RECIST v1.1, plus an additional category of early death). The best overall response was then determined. A subject was defined as having an objective response if they had a best overall response of CR or PR prior to receiving any subsequent anticancer therapy; confirmed response is confirmation of CR or PR at least 4 weeks from the initial determination per RECIST v1.1. Subjects with a post-baseline assessment were included in the calculations for objective response rate (ORR). Outcome is based on data reported by Investigator (INV); available and evaluable radiographic scans were collected retrospectively for review by an Independent Review Committee (IRC).

Time frame: From first dose of rovalpituzumab tesirine to last event, up through study completion (on average approximately 4 months).

Population: Subjects with at least one post-dose assessment. All LCNEC subjects were analyzed. No LCNEC subjects achieved CR or PR and, therefore, the ORR was 0%.

ArmMeasureGroupValue (NUMBER)
Rovalpituzumab TesirineObjective Response Rate (ORR)ORR unconfirmed by Investigator25 percentage of subjects
Rovalpituzumab TesirineObjective Response Rate (ORR)ORR confirmed by Investigator17 percentage of subjects
Rovalpituzumab TesirineObjective Response Rate (ORR)ORR unconfirmed by IRC27 percentage of subjects
Rovalpituzumab TesirineObjective Response Rate (ORR)ORR confirmed by IRC16 percentage of subjects
LCNEC SubjectsObjective Response Rate (ORR)ORR confirmed by IRC0 percentage of subjects
LCNEC SubjectsObjective Response Rate (ORR)ORR unconfirmed by Investigator0 percentage of subjects
LCNEC SubjectsObjective Response Rate (ORR)ORR unconfirmed by IRC0 percentage of subjects
LCNEC SubjectsObjective Response Rate (ORR)ORR confirmed by Investigator0 percentage of subjects
Secondary

Overall Survival

Overall survival (OS) was defined as the time from the first day of study treatment to death. Subjects who were alive were censored at the date of last known alive.

Time frame: From first dose of Rovalpituzumab tesirine to last event, up through study completion (on average approximately 5-7 months, but up to 14.6 months).

Population: Subjects with at least one post-dose assessment.

ArmMeasureValue (MEDIAN)
Rovalpituzumab TesirineOverall Survival4.76 months
LCNEC SubjectsOverall Survival6.59 months
Secondary

Progression-free Survival (PFS)

Progression-free survival (PFS) was defined as the number of months from the first day of study drug administration to disease recurrence or progression, or death on study. Outcome is based on data reported by Investigator (INV); available and evaluable radiographic scans were collected retrospectively for review by an Independent Review Committee (IRC).

Time frame: From first dose of rovalpituzumab tesirine to last event timepoint, up through study completion (approximately 4 months on average, but up to 14.46 months).

Population: Subjects with at least one post-dose assessment.

ArmMeasureGroupValue (MEDIAN)
Rovalpituzumab TesirineProgression-free Survival (PFS)PFS by INV2.79 months
Rovalpituzumab TesirineProgression-free Survival (PFS)PFS by IRC2.89 months
LCNEC SubjectsProgression-free Survival (PFS)PFS by INV3.07 months
LCNEC SubjectsProgression-free Survival (PFS)PFS by IRC2.6 months

Source: ClinicalTrials.gov · Data processed: Mar 11, 2026