Small Cell Lung Cancer
Conditions
Keywords
Immunogen, Lung, Small Cell Lung Cancer, Carboplatin, ADC
Brief summary
The purpose of this study is to test safety and efficacy of this combination treatment (IMGN901, carboplatin and etoposide) in patients with solid tumors and extensive stage small cell lung cancer.
Detailed description
Small-Cell Lung Cancer (SCLC) is a neuroendocrine cancer of the lung that is typically caused by smoking. Patients generally present with symptoms of cough, dyspnea, pain and weakness, and often have extensive disease at that time. It is estimated that 13% of lung cancers are SCLC in origin1. Approximately 28,530 new cases of SCLC were expected in 2009 based on an estimate of 219,440 new cases of any cancer of the lung in the US in 20092. There are 2 stages of the disease: limited-stage disease (LD) and extensive-stage disease (ED). SCLC-LD is confined to a region of the chest (the hemithorax and mediastinum) that is more amenable to radiation therapy. Thirty percent (30%) of patients present with SCLC-LD. The remaining patients (70%) present with SCLC-ED, in which the disease has progressed outside this region of the chest. Common sites of metastatic disease include the contralateral lung, liver, adrenal glands, brain, bones and/or bone marrow3. Recurrence after therapy is typical. In the rare patient who has longer-term survival, secondary malignancies (new SCLC tumors and other malignancies) are common because of long-term exposure to carcinogens. SCLC is very responsive to chemotherapy and radiation therapy, having response rates of up to 80%4-7. In limited stage disease, the standard treatment is 'combined-modality therapy' consisting of combination chemotherapy such as cisplatin plus etoposide followed by thoracic radiation therapy. Surgery is rarely used. Despite high response rates, therapy is rarely curative due to high rates of recurrence and metastasis. Overall 5-year survival for SCLC patients is 4%5. SCLC-LD patients typically achieve median survival of 14 to 24 months after therapy, with a 2-year survival rate of 40% to 50%. This survival rate drops to about 20% at 5 years4-7. SCLC-ED patients achieve a median survival of 8 to 12 months on therapy8. Patients will typically have recurrent disease after therapy. While many of these patients may be eligible for further chemotherapy, survival at this stage is usually less than 6 months. No treatment modality has a significant impact on overall survival. Studies utilizing regimens with greater numbers of chemotherapeutic agents or longer therapy duration have not improved survival. Thus, a new therapy that can improve survival is needed. IMGN901 is an antibody drug conjugate which is anticipated to result in lower systemic toxicity and greater efficacy than currently available therapies based on its specific and high affinity binding to its target antigen, CD56. This antigen has been shown to be present in almost all cases of SCLC (\ 95% based on in-house data). In in vivo studies, IMGN901 has demonstrated potent anti-tumor activity against CD56-positive carcinomas including xenograft models of SCLC as well as complete regressions when combined with cisplatin/etoposide. Preliminary clinical activity of single agent IMGN901 based on data from two Phase 1 studies shows a disease control rate (PR and SD, defined as non-progression for at least 75 days) estimated to be 24% in a heterogeneous population of patients with pretreated and drug resistant SCLC. Additional data supportive of the potential activity of IMGN901 includes complete responses and clinically relevant stable disease in patients with MCC (clinical benefit rate = 39%). Further, the tolerability profile demonstrating minimal myelosuppression with administration of IMGN901 is supportive of exploring its use in combination with established chemotherapy regimens. IMGN901 is supportive of exploring its use in combination with established chemotherapy regimens. Therefore, the Phase 1 portion of this study is designed to first determine the MTD, presumably the recommended Phase 2 dose, of IMGN901 when administered in combination with carboplatin/etoposide treatment and to characterize the safety, tolerability, PK, pharmacodynamics, immunogenicity, and preliminary anti-tumor activity of this triplet combination. Improvement in disease control and survival of patients with SCLC-ED remains a major therapeutic challenge. New agents with better activity and tolerability are needed for this population. However, because large-scale clinical studies often are necessary to demonstrate the safety and effectiveness of these new agents, it is desirable to first evaluate some measure of relative effectiveness in a Phase 2 study. Therefore the Phase 2 portion of the study will utilize a Simon two-stage design in which the activity of IMGN901 will be assessed by comparing the PFS rate at six months in the IMGN901 experimental arm (triplet combination) against the historical 6 month PFS rate of 0.44 (equivalently a median PFS = 5 months). In this study, an improvement of 2.5 months in median PFS will be deemed clinically relevant and correlates to a PFS rate of 0.58 (HR = 0.667). The control arm will be used primarily to reliably assess the safety of IMGN901 and will further serve as an informal validation of the historical data.
Interventions
DRUGIMGN901
Phase 2 regimen is IMGN901, Carboplatin, and Etoposide. IMGN901 to be given on days 1 and 8 every 21 days.
Patients assigned to Arm 2 were to receive carboplatin at the same AUC as utilized in Arm 1
Sponsors
ImmunoGen, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients must be 18 years old * Patients must have been diagnosed with small-cell lung cancer (SCLC) and extensive disease * ECOG performance status of 0, 1, or 2 * No prior systemic chemotherapy for the treatment of SCLC
Exclusion criteria
\- Pregnant or lactating females
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Occurrence of Dose Limiting Toxicities (DLT) | 21 days (Cycle 1) | The primary outcome measure for Phase I was to determine the maximum tolerated dose (MTD) and characterize the dose limiting toxicities (DLT) of IMGN901 when administered in combination with carboplatin/etoposide chemotherapy followed by IMGN901 alone in patients with solid tumors. For the purposes of dose escalation and determination of MTD, DLTs were defined as AEs or abnormal laboratory values related to study treatment which occurred in Cycle 1 of the Dose Escalation phase, including any AEs that resulted in failure to meet the criteria for re-treatment. The following events were considered DLTs (using the most current version of CTCAE): febrile neutropenia; Grade 4 thrombocytopenia or Grade 3 thrombocytopenia with bleeding; ≥ Grade 3 peripheral neuropathy; ≥ Grade 3 vomiting, nausea, or diarrhea that persisted despite the use of optimal therapy; other ≥ grade 3 non-hematologic toxicity (with the exception of brief fatigue i.e. ≤ 72 hours and alopecia) |
| Progression Free Survival (PFS) in Phase II | From randomization to objective tumor progression or death (up to post-treatment follow-up 28 days after last dose, up to 22 months) | The primary outcome measure for Phase II was to determine the efficacy of IMGN901 in combination with carboplatin/etoposide chemotherapy as first-line treatment for patients with extensive stage small cell lung cancer. PFS was defined as the time from enrollment until objective tumor progression according to RECIST 1.1 or death on study due to any cause, whichever occurred first. Only the results from the experimental arm (IMGN901 + carboplatin + etoposide) are presented as the primary objective of this phase of the study was to compare PFS in the experimental arm (triplet combination) against historical PFS rates for carboplatin and etoposide. The control arm was planned primarily to reliably assess the safety of IMGN901 and to demonstrate whether the or not the historical assumptions regarding efficacy were confirmed. |
| Maximum Tolerated Dose (MTD) of IMGN901 | 21 days (Cycle 1) | A primary outcome measure for Phase I was to determine the maximum tolerated dose (MTD) of IMGN901 when administered in combination with carboplatin/etoposide chemotherapy followed by IMGN901 alone in patients with solid tumors. The MTD was determined based on DLTs that occurred during Cycle 1. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overview of Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | From the first dose of study drug on Cycle 1, Day 1 until 28 days after the last study treatment (up to 22 months) | To assess the type and frequency of Adverse Events (AEs) and Serious Adverse Events (SAEs). An AE was defined as any noxious, pathologic, or unintended change un anatomical, physiologic, or metabolic function as indicated by physical signs, symptoms, or laboratory changes occurring in any phase of the study, whether or not deemed study drug-related. An SAE was any AE resulting in death, life-threatening experience, initial or prolonged in-patient hospitalization, persistent or significant disability/incapacity, or congenital defect. All AEs were reported from the time of the first dose of study treatment until 28 days after the final dose of study drug. the severity of AEs were graded by the Investigator using National cancer Institute (NCI) Common Terminology Criteria for AEs (CTCAE) version 4.0. |
| Overall Survival (OS) Rate at 12 Months | 12 months | OS was analyzed based on a binary definition of the number of patients dead or censored prior to 12 months and the number of patients alive at 12 months. The primary objective of this phase of the study was to compare PFS in the experimental arm (triplet combination) against historical PFS rates. The control arm was primarily planned to demonstrate whether the or not the historical assumptions regarding efficacy were confirmed. Further, the trial was not empowered to permit a statistically informative comparison of the randomized treatment groups with respect to OS and no determination of the OS rate at 12 months for the control arm was performed; therefore only the results from the experimental arm (IMGN901 + carboplatin + etoposide) are presented. |
| Progression Free Survival (PFS) Rate at 6 Months | 6 months | The trial was not empowered to permit a statistically informative comparison of the randomized treatment groups with respect to PFS. The activity of IMGN901 was assessed by comparing the PFS rate at 6 months in the IMGN901 experimental arm against the historical 6-month PFS rate of 0.44 (equivalently a median PFS = 5 months). Only the results from the experimental arm (IMGN901 + carboplatin + etoposide) are presented as the objective was to compare PFS at 6 months in the experimental arm (triplet combination) against the historical PFS rate of 0.44 (equivalently a median PFS = 5 months) for carboplatin and etoposide. The control arm was planned primarily to reliably assess the safety of IMGN901 and to demonstrate whether the or not the historical assumptions regarding efficacy were confirmed. |
| Median Overall Survival (OS) in Phase II | From the time of enrollment until death on study due to any cause (up to post-treatment follow-up 28 days after last dose, up to 22 months) | A secondary outcome measure for Phase II was to determine the overall survival of patients treated with IMGN901 in combination with carboplatin/etoposide chemotherapy versus carboplatin/etoposide chemotherapy alone as first-line treatment for patients with extensive stage small cell lung cancer. |
Countries
Canada, Spain, United Kingdom, United States
Participant flow
Recruitment details
Participants were recruited from, and treated at, 45 study sites in the U.S., Canada, Spain, and the U.K. between November 2010 and May 2015.
Pre-assignment details
Patients were screened during a 28-day period
Participants by arm
| Arm | Count |
|---|---|
| Phase I - IMGN901 + Carboplatin + Etoposide Participants received IMGN901 on Days 1 and 8 of a 21-day cycle. All patients also received carboplatin on Day 1 and etoposide on Days 1, 2, and 3 of each 21-day cycle.The starting dose of IMGN901 was 60 mg/m2; dose escalation proceeded, as tolerated, through 75, 90, and 112 mg/m2. Carboplatin was originally dosed at an AUC 6 however due to poor tolerability this was reduced to an AUC of 5. Study drug combinations were administered for four cycles, with up to 6 cycles allowed. IMGN901 was continued as monotherapy for patients who achieved a response or stable disease. | 33 |
| Phase II - IMGN901 + Carboplatin + Etoposide IMGN901 was administered at the RP2D determined in Phase I (112 mg/m2; later reduced to 90 mg/m2) on Days 1 and 8 of each 21-day cycle. Patients also received carboplatin (AUC 5) on Day 1 and etoposide (100 mg/m2) on Days 1, 2, and 3 of each 21-day cycle. Study drug combinations were administered for four cycles, with up to 6 cycles allowed. IMGN901 was continued as monotherapy for patients who achieved a response or stable disease. | 94 |
| Phase II - Carboplatin + Etoposide Carboplatin (AUC 5) was administered on Day 1 and etoposide (100 mg/m2) on Days 1, 2, and 3 of each 21-day cycle. Drugs were administered for 6 cycles as tolerated. | 47 |
| Total | 174 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Phase II | Adverse Event | 0 | 39 | 9 |
| Phase II | Completed Cycles 4-6 | 0 | 11 | 21 |
| Phase II | Death | 0 | 0 | 2 |
| Phase II | Lack of Efficacy | 0 | 25 | 3 |
| Phase II | Randomized but were not treated | 0 | 4 | 3 |
| Phase II | Sponsor Decision/Study Closed | 0 | 18 | 7 |
| Phase II | Withdrawal by Subject | 0 | 1 | 5 |
| Phase I - IMGN901+Carboplatin+Etoposide | Adverse Event | 5 | 0 | 0 |
| Phase I - IMGN901+Carboplatin+Etoposide | Incorrect Original Diagnosis | 1 | 0 | 0 |
| Phase I - IMGN901+Carboplatin+Etoposide | Lack of Efficacy | 24 | 0 | 0 |
| Phase I - IMGN901+Carboplatin+Etoposide | Withdrawal by Subject | 3 | 0 | 0 |
Baseline characteristics
| Characteristic | Phase I - IMGN901 + Carboplatin + Etoposide | Phase II - IMGN901 + Carboplatin + Etoposide | Phase II - Carboplatin + Etoposide | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 12 Participants | 45 Participants | 21 Participants | 78 Participants |
| Age, Categorical Between 18 and 65 years | 21 Participants | 49 Participants | 26 Participants | 96 Participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status 0 | 14 Participants | 22 Participants | 12 Participants | 48 Participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status 1 | 19 Participants | 62 Participants | 32 Participants | 113 Participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status 2 | 0 Participants | 10 Participants | 3 Participants | 13 Participants |
| History of Smoking No | 12 participants | 1 participants | 1 participants | 14 participants |
| History of Smoking Yes | 21 participants | 93 participants | 46 participants | 160 participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 3 Participants | 2 Participants | 7 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 30 Participants | 90 Participants | 44 Participants | 164 Participants |
| Sex: Female, Male Female | 20 Participants | 40 Participants | 22 Participants | 82 Participants |
| Sex: Female, Male Male | 13 Participants | 54 Participants | 25 Participants | 92 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 33 / 33 | 91 / 94 | 43 / 47 |
| serious Total, serious adverse events | 16 / 33 | 54 / 94 | 23 / 47 |
Outcome results
Primary
Maximum Tolerated Dose (MTD) of IMGN901
A primary outcome measure for Phase I was to determine the maximum tolerated dose (MTD) of IMGN901 when administered in combination with carboplatin/etoposide chemotherapy followed by IMGN901 alone in patients with solid tumors. The MTD was determined based on DLTs that occurred during Cycle 1.
Time frame: 21 days (Cycle 1)
Population: During escalation, carboplatin dosing was reduced from AUC 6 to AUC 5 due to poor tolerability; therefore the MTD for IMGN901 was determined in combination with carboplatin AUC5 and 100 mg/m\^2 etoposide
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IMGN901 60 mg/m2 + Carboplatin AUC 6 + Etoposide 100 mg/m2 | Maximum Tolerated Dose (MTD) of IMGN901 | 112 mg/m^2 |
Primary
Occurrence of Dose Limiting Toxicities (DLT)
The primary outcome measure for Phase I was to determine the maximum tolerated dose (MTD) and characterize the dose limiting toxicities (DLT) of IMGN901 when administered in combination with carboplatin/etoposide chemotherapy followed by IMGN901 alone in patients with solid tumors. For the purposes of dose escalation and determination of MTD, DLTs were defined as AEs or abnormal laboratory values related to study treatment which occurred in Cycle 1 of the Dose Escalation phase, including any AEs that resulted in failure to meet the criteria for re-treatment. The following events were considered DLTs (using the most current version of CTCAE): febrile neutropenia; Grade 4 thrombocytopenia or Grade 3 thrombocytopenia with bleeding; ≥ Grade 3 peripheral neuropathy; ≥ Grade 3 vomiting, nausea, or diarrhea that persisted despite the use of optimal therapy; other ≥ grade 3 non-hematologic toxicity (with the exception of brief fatigue i.e. ≤ 72 hours and alopecia)
Time frame: 21 days (Cycle 1)
Population: A total of 33 patients were analyzed as part of the Dose escalation phase.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| IMGN901 60 mg/m2 + Carboplatin AUC 6 + Etoposide 100 mg/m2 | Occurrence of Dose Limiting Toxicities (DLT) | Grade 4 granulocytopenia | 0 participants |
| IMGN901 60 mg/m2 + Carboplatin AUC 6 + Etoposide 100 mg/m2 | Occurrence of Dose Limiting Toxicities (DLT) | Grade 3 febrile neutropenia | 0 participants |
| IMGN901 60 mg/m2 + Carboplatin AUC 6 + Etoposide 100 mg/m2 | Occurrence of Dose Limiting Toxicities (DLT) | Grade 3 lobar pneumonia | 0 participants |
| IMGN901 60 mg/m2 + Carboplatin AUC 6 + Etoposide 100 mg/m2 | Occurrence of Dose Limiting Toxicities (DLT) | Grade 4 febrile neutropenia | 1 participants |
| IMGN901 60 mg/m2 + Carboplatin AUC 6 + Etoposide 100 mg/m2 | Occurrence of Dose Limiting Toxicities (DLT) | Grade 4 thrombocytopenia | 0 participants |
| IMGN901 75 mg/m2 + Carboplatin AUC 6 + Etoposide 100 mg/m2 | Occurrence of Dose Limiting Toxicities (DLT) | Grade 4 granulocytopenia | 1 participants |
| IMGN901 75 mg/m2 + Carboplatin AUC 6 + Etoposide 100 mg/m2 | Occurrence of Dose Limiting Toxicities (DLT) | Grade 4 thrombocytopenia | 2 participants |
| IMGN901 75 mg/m2 + Carboplatin AUC 6 + Etoposide 100 mg/m2 | Occurrence of Dose Limiting Toxicities (DLT) | Grade 4 febrile neutropenia | 1 participants |
| IMGN901 75 mg/m2 + Carboplatin AUC 6 + Etoposide 100 mg/m2 | Occurrence of Dose Limiting Toxicities (DLT) | Grade 3 lobar pneumonia | 0 participants |
| IMGN901 75 mg/m2 + Carboplatin AUC 6 + Etoposide 100 mg/m2 | Occurrence of Dose Limiting Toxicities (DLT) | Grade 3 febrile neutropenia | 1 participants |
| IMGN901 75 mg/m2 + Carboplatin AUC 5 + Etoposide 100 mg/m2 | Occurrence of Dose Limiting Toxicities (DLT) | Grade 4 thrombocytopenia | 0 participants |
| IMGN901 75 mg/m2 + Carboplatin AUC 5 + Etoposide 100 mg/m2 | Occurrence of Dose Limiting Toxicities (DLT) | Grade 3 febrile neutropenia | 0 participants |
| IMGN901 75 mg/m2 + Carboplatin AUC 5 + Etoposide 100 mg/m2 | Occurrence of Dose Limiting Toxicities (DLT) | Grade 4 febrile neutropenia | 0 participants |
| IMGN901 75 mg/m2 + Carboplatin AUC 5 + Etoposide 100 mg/m2 | Occurrence of Dose Limiting Toxicities (DLT) | Grade 4 granulocytopenia | 0 participants |
| IMGN901 75 mg/m2 + Carboplatin AUC 5 + Etoposide 100 mg/m2 | Occurrence of Dose Limiting Toxicities (DLT) | Grade 3 lobar pneumonia | 0 participants |
| IMGN901 90 mg/m2 + Carboplatin AUC 5 + Etoposide 100 mg/m2 | Occurrence of Dose Limiting Toxicities (DLT) | Grade 3 lobar pneumonia | 0 participants |
| IMGN901 90 mg/m2 + Carboplatin AUC 5 + Etoposide 100 mg/m2 | Occurrence of Dose Limiting Toxicities (DLT) | Grade 3 febrile neutropenia | 0 participants |
| IMGN901 90 mg/m2 + Carboplatin AUC 5 + Etoposide 100 mg/m2 | Occurrence of Dose Limiting Toxicities (DLT) | Grade 4 granulocytopenia | 0 participants |
| IMGN901 90 mg/m2 + Carboplatin AUC 5 + Etoposide 100 mg/m2 | Occurrence of Dose Limiting Toxicities (DLT) | Grade 4 thrombocytopenia | 1 participants |
| IMGN901 90 mg/m2 + Carboplatin AUC 5 + Etoposide 100 mg/m2 | Occurrence of Dose Limiting Toxicities (DLT) | Grade 4 febrile neutropenia | 1 participants |
| IMGN901 112 mg/m2 + Carboplatin AUC 5 + Etoposide 100 mg/m2 | Occurrence of Dose Limiting Toxicities (DLT) | Grade 4 thrombocytopenia | 1 participants |
| IMGN901 112 mg/m2 + Carboplatin AUC 5 + Etoposide 100 mg/m2 | Occurrence of Dose Limiting Toxicities (DLT) | Grade 4 granulocytopenia | 0 participants |
| IMGN901 112 mg/m2 + Carboplatin AUC 5 + Etoposide 100 mg/m2 | Occurrence of Dose Limiting Toxicities (DLT) | Grade 3 febrile neutropenia | 0 participants |
| IMGN901 112 mg/m2 + Carboplatin AUC 5 + Etoposide 100 mg/m2 | Occurrence of Dose Limiting Toxicities (DLT) | Grade 3 lobar pneumonia | 1 participants |
| IMGN901 112 mg/m2 + Carboplatin AUC 5 + Etoposide 100 mg/m2 | Occurrence of Dose Limiting Toxicities (DLT) | Grade 4 febrile neutropenia | 0 participants |
Primary
Progression Free Survival (PFS) in Phase II
The primary outcome measure for Phase II was to determine the efficacy of IMGN901 in combination with carboplatin/etoposide chemotherapy as first-line treatment for patients with extensive stage small cell lung cancer. PFS was defined as the time from enrollment until objective tumor progression according to RECIST 1.1 or death on study due to any cause, whichever occurred first. Only the results from the experimental arm (IMGN901 + carboplatin + etoposide) are presented as the primary objective of this phase of the study was to compare PFS in the experimental arm (triplet combination) against historical PFS rates for carboplatin and etoposide. The control arm was planned primarily to reliably assess the safety of IMGN901 and to demonstrate whether the or not the historical assumptions regarding efficacy were confirmed.
Time frame: From randomization to objective tumor progression or death (up to post-treatment follow-up 28 days after last dose, up to 22 months)
Population: A total of 82 patients from the IMGN901 + carboplatin + etoposide safety population (N=94) were included in the efficacy analyses, due to the lack of post-baseline evaluations for 12 participants.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| IMGN901 60 mg/m2 + Carboplatin AUC 6 + Etoposide 100 mg/m2 | Progression Free Survival (PFS) in Phase II | 6.2 months |
Secondary
Median Overall Survival (OS) in Phase II
A secondary outcome measure for Phase II was to determine the overall survival of patients treated with IMGN901 in combination with carboplatin/etoposide chemotherapy versus carboplatin/etoposide chemotherapy alone as first-line treatment for patients with extensive stage small cell lung cancer.
Time frame: From the time of enrollment until death on study due to any cause (up to post-treatment follow-up 28 days after last dose, up to 22 months)
Population: A total of 121 patents were included in the analyses (82 in Arm1 and 39 in Arm 2) due to due to the lack of post-baseline evaluations for 20 participants.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| IMGN901 60 mg/m2 + Carboplatin AUC 6 + Etoposide 100 mg/m2 | Median Overall Survival (OS) in Phase II | 10.1 months |
| IMGN901 75 mg/m2 + Carboplatin AUC 6 + Etoposide 100 mg/m2 | Median Overall Survival (OS) in Phase II | 10.97 months |
Secondary
Overall Survival (OS) Rate at 12 Months
OS was analyzed based on a binary definition of the number of patients dead or censored prior to 12 months and the number of patients alive at 12 months. The primary objective of this phase of the study was to compare PFS in the experimental arm (triplet combination) against historical PFS rates. The control arm was primarily planned to demonstrate whether the or not the historical assumptions regarding efficacy were confirmed. Further, the trial was not empowered to permit a statistically informative comparison of the randomized treatment groups with respect to OS and no determination of the OS rate at 12 months for the control arm was performed; therefore only the results from the experimental arm (IMGN901 + carboplatin + etoposide) are presented.
Time frame: 12 months
Population: A total of 82 patients from the IMGN901 + carboplatin + etoposide safety population (N=94) were included in the efficacy analyses, due to the lack of post-baseline evaluations for 12 participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IMGN901 60 mg/m2 + Carboplatin AUC 6 + Etoposide 100 mg/m2 | Overall Survival (OS) Rate at 12 Months | 61 percentage of participants alive |
Secondary
Overview of Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
To assess the type and frequency of Adverse Events (AEs) and Serious Adverse Events (SAEs). An AE was defined as any noxious, pathologic, or unintended change un anatomical, physiologic, or metabolic function as indicated by physical signs, symptoms, or laboratory changes occurring in any phase of the study, whether or not deemed study drug-related. An SAE was any AE resulting in death, life-threatening experience, initial or prolonged in-patient hospitalization, persistent or significant disability/incapacity, or congenital defect. All AEs were reported from the time of the first dose of study treatment until 28 days after the final dose of study drug. the severity of AEs were graded by the Investigator using National cancer Institute (NCI) Common Terminology Criteria for AEs (CTCAE) version 4.0.
Time frame: From the first dose of study drug on Cycle 1, Day 1 until 28 days after the last study treatment (up to 22 months)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| IMGN901 60 mg/m2 + Carboplatin AUC 6 + Etoposide 100 mg/m2 | Overview of Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Any SAE | 16 participants |
| IMGN901 60 mg/m2 + Carboplatin AUC 6 + Etoposide 100 mg/m2 | Overview of Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Any TEAE | 33 participants |
| IMGN901 60 mg/m2 + Carboplatin AUC 6 + Etoposide 100 mg/m2 | Overview of Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Related SAE | 8 participants |
| IMGN901 60 mg/m2 + Carboplatin AUC 6 + Etoposide 100 mg/m2 | Overview of Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Deaths within 28 days of last dose | 1 participants |
| IMGN901 60 mg/m2 + Carboplatin AUC 6 + Etoposide 100 mg/m2 | Overview of Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Related TEAE | 32 participants |
| IMGN901 60 mg/m2 + Carboplatin AUC 6 + Etoposide 100 mg/m2 | Overview of Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | TEAEs leading to discontinuation | 8 participants |
| IMGN901 60 mg/m2 + Carboplatin AUC 6 + Etoposide 100 mg/m2 | Overview of Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Related Grade ≥ 3 TEAE | 22 participants |
| IMGN901 60 mg/m2 + Carboplatin AUC 6 + Etoposide 100 mg/m2 | Overview of Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Any Grade ≥ 3 TEAE | 29 participants |
| IMGN901 75 mg/m2 + Carboplatin AUC 6 + Etoposide 100 mg/m2 | Overview of Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Related TEAE | 90 participants |
| IMGN901 75 mg/m2 + Carboplatin AUC 6 + Etoposide 100 mg/m2 | Overview of Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Any Grade ≥ 3 TEAE | 92 participants |
| IMGN901 75 mg/m2 + Carboplatin AUC 6 + Etoposide 100 mg/m2 | Overview of Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Any TEAE | 94 participants |
| IMGN901 75 mg/m2 + Carboplatin AUC 6 + Etoposide 100 mg/m2 | Overview of Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Related Grade ≥ 3 TEAE | 83 participants |
| IMGN901 75 mg/m2 + Carboplatin AUC 6 + Etoposide 100 mg/m2 | Overview of Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Deaths within 28 days of last dose | 14 participants |
| IMGN901 75 mg/m2 + Carboplatin AUC 6 + Etoposide 100 mg/m2 | Overview of Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Any SAE | 54 participants |
| IMGN901 75 mg/m2 + Carboplatin AUC 6 + Etoposide 100 mg/m2 | Overview of Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Related SAE | 30 participants |
| IMGN901 75 mg/m2 + Carboplatin AUC 6 + Etoposide 100 mg/m2 | Overview of Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | TEAEs leading to discontinuation | 50 participants |
| IMGN901 75 mg/m2 + Carboplatin AUC 5 + Etoposide 100 mg/m2 | Overview of Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Deaths within 28 days of last dose | 5 participants |
| IMGN901 75 mg/m2 + Carboplatin AUC 5 + Etoposide 100 mg/m2 | Overview of Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Any TEAE | 46 participants |
| IMGN901 75 mg/m2 + Carboplatin AUC 5 + Etoposide 100 mg/m2 | Overview of Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Related TEAE | 39 participants |
| IMGN901 75 mg/m2 + Carboplatin AUC 5 + Etoposide 100 mg/m2 | Overview of Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Any SAE | 23 participants |
| IMGN901 75 mg/m2 + Carboplatin AUC 5 + Etoposide 100 mg/m2 | Overview of Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Related SAE | 9 participants |
| IMGN901 75 mg/m2 + Carboplatin AUC 5 + Etoposide 100 mg/m2 | Overview of Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | TEAEs leading to discontinuation | 6 participants |
| IMGN901 75 mg/m2 + Carboplatin AUC 5 + Etoposide 100 mg/m2 | Overview of Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Any Grade ≥ 3 TEAE | 42 participants |
| IMGN901 75 mg/m2 + Carboplatin AUC 5 + Etoposide 100 mg/m2 | Overview of Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Related Grade ≥ 3 TEAE | 33 participants |
Secondary
Progression Free Survival (PFS) Rate at 6 Months
The trial was not empowered to permit a statistically informative comparison of the randomized treatment groups with respect to PFS. The activity of IMGN901 was assessed by comparing the PFS rate at 6 months in the IMGN901 experimental arm against the historical 6-month PFS rate of 0.44 (equivalently a median PFS = 5 months). Only the results from the experimental arm (IMGN901 + carboplatin + etoposide) are presented as the objective was to compare PFS at 6 months in the experimental arm (triplet combination) against the historical PFS rate of 0.44 (equivalently a median PFS = 5 months) for carboplatin and etoposide. The control arm was planned primarily to reliably assess the safety of IMGN901 and to demonstrate whether the or not the historical assumptions regarding efficacy were confirmed.
Time frame: 6 months
Population: A total of 82 patients from the IMGN901 + carboplatin + etoposide safety population (N=94) were included in the efficacy analyses, due to the lack of post-baseline evaluations for 12 participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IMGN901 60 mg/m2 + Carboplatin AUC 6 + Etoposide 100 mg/m2 | Progression Free Survival (PFS) Rate at 6 Months | 39 percentage of participants |