Non-squamous Non-small-cell Lung Cancer (NSQ NSCLC)
Conditions
Brief summary
Primary Objective: * Safety run-in part: to assess the tolerability and to determine the recommended doses of tusamitamab ravtansine in combination with pembrolizumab and tusamitamab ravtansine in combination with pembrolizumab and platinum-based chemotherapy with or without pemetrexed to be tested in the expansion part of the study in the NSQ NSCLC population * Expansion part (including participants treated at the recommended dose for expansion \[RDE\] from the Safety Run-in part): to assess the antitumor activity of several dose levels (DLs; if applicable) of tusamitamab ravtansine in combination with pembrolizumab and of several DLs of tusamitamab ravtansine in combination with pembrolizumab, platinum-based chemotherapy, and pemetrexed in the NSQ NSCLC population Secondary Objectives: * To assess the safety and tolerability of several DLs (if applicable) of tusamitamab ravtansine in combination with pembrolizumab and of 1 DL of tusamitamab ravtansine in combination with pembrolizumab and platinum-based chemotherapy, and of several DLs of tusamitamab ravtansine in combination with pembrolizumab, and platinum-based chemotherapy with pemetrexed in the NSQ NSCLC population * To assess the antitumor activity of several DLs (if applicable) of tusamitamab ravtansine in combination with pembrolizumab and of 1 DL of tusamitamab ravtansine in combination with pembrolizumab and platinum-based chemotherapy, and of several DLs of tusamitamab ravtansine in combination with pembrolizumab, platinum-based chemotherapy, and pemetrexed in the NSQ NSCLC population * To assess the durability of the response to treatment with several DLs (if applicable) of tusamitamab ravtansine in combination with pembrolizumab and of 1 DL of tusamitamab ravtansine in combination with pembrolizumab and platinum-based chemotherapy, and of several DLs of tusamitamab ravtansine in combination with pembrolizumab and platinum-based chemotherapy, and pemetrexed in the NSQ NSCLC population * To assess the antitumor activity of tusamitamab ravtansine in combination with pembrolizumab and platinum-based chemotherapy in the NSQ NSCLC population * To assess the pharmacokinetics (PK) of tusamitamab ravtansine, pembrolizumab, pemetrexed, cisplatin, and carboplatin, each when given in combination as a doublet (tusamitamab ravtansine + pembrolizumab) or a triplet (tusamitamab ravtansine + pembrolizumab + platinum-based chemotherapy) or a quadruplet (tusamitamab ravtansine + pembrolizumab + platinum-based chemotherapy + pemetrexed) * To assess the immunogenicity of tusamitamab ravtansine in combination with pembrolizumab and tusamitamab ravtansine in combination with pembrolizumab and platinum based chemotherapy with or without pemetrexed
Detailed description
The expected duration of study intervention for participants may vary, based on disease progression date; median expected duration of study per participant is estimated at 10 months (up to 1 month for screening, a median of 6 months for treatment, a median of 1 month for EOT, and follow-up visit 90 days after the last IMP administration).
Interventions
DRUGSAR408701 (Tusamitamab ravtansine)
Pharmaceutical form:Concentrate for solution for infusion Route of administration: Intravenous
DRUGPembrolizumab
Pharmaceutical form: Concentrate for solution for infusion Route of administration: Intravenous
DRUGCisplatin
Pharmaceutical form: Lyophilized powder for reconstitution in solution Route of administration: Intravenous
DRUGCarboplatin
Pharmaceutical form: Concentrate for solution for infusion Route of administration: Intravenous
DRUGPemetrexed
Pharmaceutical form: Concentrate for solution for infusion Route of administration: Intravenous
Sponsors
Sanofi
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
: * Histologically- or cytologically-confirmed diagnosis of advanced or metastatic NSQ NSCLC with no EGFR sensitizing mutation or BRAF mutation or ALK/ROS alterations. * No prior systemic chemotherapy for the treatment of the participant's advanced or metastatic disease (treatment with chemotherapy and/or radiation as part of neoadjuvant/adjuvant therapy is allowed as long as completed at least 6 months prior to diagnosis of advanced or metastatic disease). * Expression of CEACAM5 as demonstrated prospectively by a centrally assessed Immunohistochemistry (IHC) assay of ≥2+ in intensity involving at least 1% of the tumor cell population in archival tumor sample (or if not available fresh biopsy sample). * Measurable disease based on RECIST 1.1. * Eastern Cooperative Oncology Group (ECOG) performance status 0-1 * Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies * Life expectancy of at least 3 months
Exclusion criteria
* Medical condition requiring concomitant administration of a medication with a strong CYP3A inhibitor. * Uncontrolled brain metastases and history of leptomeningeal disease. * Significant concomitant illness, including any severe medical condition that, in the opinion of the investigator or Sponsor, would impair the patient's participation in the study or interpretation of the results. * History within the last 3 years of an invasive malignancy other than the one treated in this study, with the exception of resected/ablated basal or squamous-cell carcinoma of the skin or carcinoma in situ of the cervix, or other local tumors considered cured by local treatment. * History of known acquired immunodeficiency syndrome (AIDS) related illnesses or known HIV disease requiring antiretroviral treatment, or active hepatitis A, B, or C infection. * History of active autoimmune disease that has required systemic treatment in the past 2 years. * History of allogeneic tissue/solid organ transplantation. * Active infection requiring IV systemic therapy within 2 weeks prior to randomization or active tuberculosis. * Interstitial lung disease or history of pneumonitis that has required oral or IV steroids * Non-resolution of any prior treatment-related toxicity to \< Grade 2 according to NCI CTCAE V5.0, with the exception of alopecia, vitiligo, or active thyroiditis controlled with hormone replacement therapy. * Unresolved corneal disorder or any previous corneal disorder considered by an ophthalmologist to predict higher risk of drug-induced keratopathy. The use of contact lenses is not permitted. * Symptomatic herpes zoster within 3 months prior to screening. * Significant allergies to humanized monoclonal antibodies. * Clinically significant multiple or severe drug allergies, intolerance to topical corticosteroids, or severe post-treatment hypersensitivity reactions (including, but not limited to, erythema multiforme major, linear immunoglobulin A \[IgA\] dermatosis, toxic epidermal necrolysis, and exfoliative dermatitis). * Concurrent treatment with any other anticancer therapy. * Have received prior chemotherapy treatment for advanced/metastatic NSCLC. * The patient is a candidate for a curative treatment with either surgical resection and/or chemoradiation * Washout period before the first administration of study intervention of less than 3 weeks or less than 5 times the half-life, whichever is shorter, for any investigational treatment). * Any prior therapy targeting CEACAM5. * Any prior treatment with any other anti-PD-1, or PD-L1 or programmed death ligand 2 (PD-L2), anti-CD137, or anti-cytotoxic T-lymphocyte-associated antigen-4. * Any prior maytansinoid treatment (DM1 or DM4 ADC). * Is receiving systemic steroid therapy ≤3 days prior to the first dose of study therapy or receiving any other form of immunosuppressive medication. Daily steroid replacement therapy or any corticosteroid premedication if applicable are allowed. * Any radiation therapy to lung \>30 Gy within 6 months of first study intervention administration. * Has received or will receive a live vaccine within 30 days prior to the first study intervention administration. * Any major surgery within the preceding 3 weeks of the first study intervention administration. Prior/concurrent clinical study experience * Current participation in any other clinical study involving an investigational study treatment or any other type of medical research. * Poor organ function The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| All Cohorts: Number of Participants With Study Drug-Related Dose-Limiting Toxicities (DLTs) | Cycle 1 Day 1 up to Cycle 1 Day 21 (cycle duration=3 weeks) | DLTs were defined as: a) Hematological abnormalities: grade 4 neutropenia for 7 or more consecutive days, grade 3 to 4 neutropenia complicated by fever (temperature ≥38.5 degree Celsius on more than 1 occasion) or microbiologically or radiographically documented infection, grade ≥3 thrombocytopenia associated with clinically significant bleeding requiring clinical intervention; b) Non-hematological abnormalities: grade 4 non-hematologic adverse event (AE), except AE symptoms related to the underlying disease as per the Investigator's judgment, grade ≥3 keratopathy. In addition, any other AE that the recruiting Investigators and sponsor deemed to be dose-limiting, regardless of its grade, was also considered as DLT. |
| Doublet Cohort: Objective Response Rate (ORR) | Tumor assessments performed at baseline, then every 6 weeks for first 24 weeks, and every 9 weeks thereafter, approximately 158.4 weeks | ORR was defined as the percentage of participants with a confirmed complete response (CR) or partial response (PR) as best overall response (BOR) per response evaluation criteria in solid tumors (RECIST) version (v) 1.1. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 millimeter (mm). PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. |
| Quadruplet Cohort: Objective Response Rate | Tumor assessments performed at baseline, then every 6 weeks for first 24 weeks, and every 9 weeks thereafter, approximately 139.9 weeks | ORR was defined as the percentage of participants with a confirmed CR or PR as per RECIST v1.1. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| All Cohorts: Duration of Response (DOR) | Tumor assessments performed at baseline, then every 6 weeks for first 24 weeks, and every 9 weeks thereafter, approximately 158.4 weeks (doublet), 113 weeks (triplet), and 139.9 weeks (quadruplet) | DOR was defined as the time from first documented evidence of CR or PR until PD determined per RECIST v1.1 or death from any cause, whichever occurred first. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (including the baseline sum if that was the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Appearance of 1 or more new lesions was also considered progression. |
| Triplet Cohort: Objective Response Rate | Tumor assessments performed at baseline, then every 6 weeks for first 24 weeks, and every 9 weeks thereafter, approximately 113 weeks | ORR was defined as the percentage of participants with a confirmed CR or PR as per RECIST v1.1. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. |
| All Cohorts: Trough Concentration (Ctrough) of Tusamitamab Ravtansine | Pre-dose on Day 1 of Cycle 2 (cycle duration=3 weeks) | Blood samples were collected for the measurement of tusamitamab ravtansine concentrations. |
| All Cohorts: Ctrough of Pembrolizumab | Pre-dose on Day 1 of Cycle 2 (cycle duration=3 weeks) | Blood samples were collected for the measurement of pembrolizumab concentrations. |
| All Cohorts: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) | From first dose of study treatment (Day 1) up to 30 days post last dose of study treatment, approximately 162.4 weeks (doublet), 117 weeks (triplet), and 143.9 weeks (quadruplet) | An AE was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. A serious AE was defined as any untoward medical occurrence that, at any dose resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent disability/incapacity or was a congenital anomaly/birth defect. A TEAE was defined as an AE that developed, worsened or became serious during the treatment-emergent period. |
| Triplet and Quadruplet Cohorts: Total Plasma Concentration Observed at the End of Infusion (Ceoi) of Cisplatin | At end of infusion on Day 1 of Cycle 1 (cycle duration=3 weeks) | Blood samples were collected for the measurement of cisplatin concentrations. |
| Triplet and Quadruplet Cohorts: Total Plasma Concentration Observed at the End of Infusion of Carboplatin | At end of infusion on Day 1 of Cycle 1 (cycle duration=3 weeks) | Blood samples were collected for the measurement of carboplatin concentrations. |
| All Cohorts: Number of Participants With Treatment-emergent Anti-Therapeutic Antibodies (ATAs) Against Tusamitamab Ravtansine | From first dose of study treatment (Day 1) up to 30 days post last dose of study treatment, approximately 162.4 weeks (doublet), 117 weeks (triplet), and 143.9 weeks (quadruplet) | Blood samples were collected to assess the presence of treatment-emergent ATA against tusamitamab ravtansine. ATA incidence was defined as the number of participants found to have treatment-emergent ATA response during the study. |
| Quadruplet Cohort: Plasma Concentration of Pemetrexed | 30 minutes post-dose on Day 1 of Cycle 1 (cycle duration=3 weeks) | Blood samples were collected for the measurement of pemetrexed concentrations. |
| Doublet and Quadruplet Cohorts: Progression-free Survival (PFS) | Tumor assessments performed at baseline, then every 6 weeks for first 24 weeks, and every 9 weeks thereafter, approximately 158.4 weeks (doublet) and 139.9 weeks (quadruplet) | PFS was defined as the time from the first study treatment administration to the date of the first documented progressive disease (PD) or death due to any cause, whichever came first. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (including the baseline sum if that was the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Appearance of 1 or more new lesions was also considered progression. |
| All Cohorts: Disease Control Rate (DCR) | Tumor assessments performed at baseline, then every 6 weeks for first 24 weeks, and every 9 weeks thereafter, approximately 158.4 weeks (doublet), 113 weeks (triplet), and 139.9 weeks (quadruplet) | DCR was defined as percentage of participants with a confirmed CR, confirmed PR or stable disease (SD) as BOR per RECIST v1.1. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD was defined as neither sufficient shrinkage from the baseline study to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (including the baseline sum if that was the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Appearance of 1 or more new lesions was also considered progression. |
Countries
Brazil, Chile, Czechia, France, Hungary, Israel, Spain, United States
Participant flow
Recruitment details
The study was conducted at 22 centers in 8 countries. A total of 68 participants were screened from 26 October 2020 to 19 December 2023, of which 11 were screen failures. Screen failures were mainly due to not meeting the eligibility criteria. The study was terminated due to the discontinuation of the overall development of tusamitamab ravtansine by the Sponsor.
Pre-assignment details
A total of 57 participants were enrolled in either Part A \[doublet cohort (tusamitamab ravtansine + pembrolizumab)\], Part B \[triplet cohort (tusamitamab ravtansine + pembrolizumab + platinum-based chemotherapy i.e., cisplatin or carboplatin)\] or Part C \[quadruplet cohort (tusamitamab ravtansine + pembrolizumab + platinum-based chemotherapy + pemetrexed)\] of the study per Investigator's choice.
Participants by arm
| Arm | Count |
|---|---|
| Tusamitamab Ravtansine 150 mg/m^2 + Pembrolizumab In Part A (doublet cohort), participants received tusamitamab ravtansine 150 mg/m\^2 along with pembrolizumab 200 mg via IV infusion on Day 1 and then Q3W until confirmed disease progression, unacceptable toxicity, new anticancer therapy initiation, death, or the participant's or Investigator's decision to stop the treatment. | 23 |
| Tusamitamab Ravtansine 170 mg/m^2 + Pembrolizumab In Part A (doublet cohort), participants received tusamitamab ravtansine 170 mg/m\^2 along with pembrolizumab 200 mg via IV infusion on Day 1 and then Q3W until confirmed disease progression, unacceptable toxicity, new anticancer therapy initiation, death, or the participant's or Investigator's decision to stop the treatment. | 2 |
| Tusamitamab Ravtansine 150 mg/m^2 + Pembrolizumab + Cisplatin/Carboplatin In Part B (triplet cohort), participants received tusamitamab ravtansine 150 mg/m\^2 along with pembrolizumab 200 mg and either cisplatin 75 mg/m\^2 or carboplatin AUC 5 via IV infusion on Day 1 of the first 4 cycles (each cycle was 3 weeks), and then tusamitamab ravtansine 150 mg/m\^2 along with pembrolizumab 200 mg via IV infusion on Day 1 of subsequent cycles until confirmed disease progression, unacceptable toxicity, new anticancer therapy initiation, death, or the participant's or Investigator's decision to stop the treatment. | 6 |
| Tusamitamab Ravtansine 170 mg/m^2 + Pembrolizumab + Cisplatin/Carboplatin In Part B (triplet cohort), participants received tusamitamab ravtansine 170 mg/m\^2 along with pembrolizumab 200 mg and either cisplatin 75 mg/m\^2 or carboplatin AUC 5 via IV infusion on Day 1 of the first 4 cycles (each cycle was 3 weeks), and then tusamitamab ravtansine 170 mg/m\^2 along with pembrolizumab 200 mg via IV infusion on Day 1 of subsequent cycles until confirmed disease progression, unacceptable toxicity, new anticancer therapy initiation, death, or the participant's or Investigator's decision to stop the treatment. | 1 |
| Tusamitamab Ravtansine 150 mg/m^2 + Pembrolizumab + Cisplatin/Carboplatin + Pemetrexed In Part C (quadruplet cohort), participants received tusamitamab ravtansine 150 mg/m\^2 along with pembrolizumab 200 mg, pemetrexed 500 mg/m\^2, and either cisplatin 75 mg/m\^2 or carboplatin AUC 5 via IV infusion on Day 1 of the first 4 cycles (each cycle was 3 weeks), and then tusamitamab ravtansine 150 mg/m\^2 along with pembrolizumab 200 mg and pemetrexed 500 mg/m\^2 via IV infusion on Day 1 of subsequent cycles until confirmed disease progression, unacceptable toxicity, new anticancer therapy initiation, death, or the participant's or Investigator's decision to stop the treatment. | 22 |
| Tusamitamab Ravtansine 170 mg/m^2 + Pembrolizumab + Cisplatin/Carboplatin + Pemetrexed In Part C (quadruplet cohort), participants received tusamitamab ravtansine 170 mg/m\^2 along with pembrolizumab 200 mg, pemetrexed 500 mg/m\^2, and either cisplatin 75 mg/m\^2 or carboplatin AUC 5 via IV infusion on Day 1 of the first 4 cycles (each cycle was 3 weeks), and then tusamitamab ravtansine 170 mg/m\^2 along with pembrolizumab 200 mg and pemetrexed 500 mg/m\^2 via IV infusion on Day 1 of subsequent cycles until confirmed disease progression, unacceptable toxicity, new anticancer therapy initiation, death, or the participant's or Investigator's decision to stop the treatment. | 3 |
| Total | 57 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Not related to Coronavirus disease 2019 | 9 | 0 | 1 | 0 | 0 | 1 |
| Overall Study | Study terminated by Sponsor | 6 | 0 | 1 | 0 | 4 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 1 | 0 | 0 | 2 | 0 |
Baseline characteristics
| Characteristic | Tusamitamab Ravtansine 150 mg/m^2 + Pembrolizumab | Tusamitamab Ravtansine 170 mg/m^2 + Pembrolizumab | Tusamitamab Ravtansine 150 mg/m^2 + Pembrolizumab + Cisplatin/Carboplatin | Tusamitamab Ravtansine 170 mg/m^2 + Pembrolizumab + Cisplatin/Carboplatin | Tusamitamab Ravtansine 150 mg/m^2 + Pembrolizumab + Cisplatin/Carboplatin + Pemetrexed | Tusamitamab Ravtansine 170 mg/m^2 + Pembrolizumab + Cisplatin/Carboplatin + Pemetrexed | Total |
|---|---|---|---|---|---|---|---|
| Age, Customized 65 to 74 years | 9 Participants | 2 Participants | 1 Participants | 1 Participants | 12 Participants | 1 Participants | 26 Participants |
| Age, Customized < 65 years | 10 Participants | 0 Participants | 3 Participants | 0 Participants | 9 Participants | 2 Participants | 24 Participants |
| Age, Customized ≥ 75 years | 4 Participants | 0 Participants | 2 Participants | 0 Participants | 1 Participants | 0 Participants | 7 Participants |
| Race/Ethnicity, Customized Multiple | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Not reported | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 8 Participants | 0 Participants | 9 Participants |
| Race/Ethnicity, Customized Unknown | 2 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 4 Participants |
| Race/Ethnicity, Customized White | 20 Participants | 2 Participants | 4 Participants | 1 Participants | 13 Participants | 3 Participants | 43 Participants |
| Sex: Female, Male Female | 11 Participants | 1 Participants | 3 Participants | 0 Participants | 9 Participants | 1 Participants | 25 Participants |
| Sex: Female, Male Male | 12 Participants | 1 Participants | 3 Participants | 1 Participants | 13 Participants | 2 Participants | 32 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 5 / 23 | 0 / 2 | 2 / 6 | 1 / 1 | 11 / 22 | 0 / 3 |
| other Total, other adverse events | 22 / 23 | 2 / 2 | 6 / 6 | 1 / 1 | 19 / 22 | 3 / 3 |
| serious Total, serious adverse events | 9 / 23 | 0 / 2 | 1 / 6 | 1 / 1 | 11 / 22 | 2 / 3 |
Outcome results
Primary
All Cohorts: Number of Participants With Study Drug-Related Dose-Limiting Toxicities (DLTs)
DLTs were defined as: a) Hematological abnormalities: grade 4 neutropenia for 7 or more consecutive days, grade 3 to 4 neutropenia complicated by fever (temperature ≥38.5 degree Celsius on more than 1 occasion) or microbiologically or radiographically documented infection, grade ≥3 thrombocytopenia associated with clinically significant bleeding requiring clinical intervention; b) Non-hematological abnormalities: grade 4 non-hematologic adverse event (AE), except AE symptoms related to the underlying disease as per the Investigator's judgment, grade ≥3 keratopathy. In addition, any other AE that the recruiting Investigators and sponsor deemed to be dose-limiting, regardless of its grade, was also considered as DLT.
Time frame: Cycle 1 Day 1 up to Cycle 1 Day 21 (cycle duration=3 weeks)
Population: DLT-evaluable population included participants who received 1 cycle with at least 80% of the intended dose for each study treatment of the combination during the safety run-in at both doses of tusamitamab ravtansine in Part A (doublet cohort), Part B (triplet cohort) or Part C (quadruplet cohort).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Tusamitamab Ravtansine 150 mg/m^2 + Pembrolizumab | All Cohorts: Number of Participants With Study Drug-Related Dose-Limiting Toxicities (DLTs) | 0 Participants |
| Tusamitamab Ravtansine 170 mg/m^2 + Pembrolizumab | All Cohorts: Number of Participants With Study Drug-Related Dose-Limiting Toxicities (DLTs) | 0 Participants |
| Tusamitamab Ravtansine 150 mg/m^2 + Pembrolizumab + Cisplatin/Carboplatin | All Cohorts: Number of Participants With Study Drug-Related Dose-Limiting Toxicities (DLTs) | 0 Participants |
| Tusamitamab Ravtansine 170 mg/m^2 + Pembrolizumab + Cisplatin/Carboplatin | All Cohorts: Number of Participants With Study Drug-Related Dose-Limiting Toxicities (DLTs) | 0 Participants |
| Tusamitamab Ravtansine 150 mg/m^2 + Pembrolizumab + Cisplatin/Carboplatin + Pemetrexed | All Cohorts: Number of Participants With Study Drug-Related Dose-Limiting Toxicities (DLTs) | 0 Participants |
| Tusamitamab Ravtansine 170 mg/m^2 + Pembrolizumab + Cisplatin/Carboplatin + Pemetrexed | All Cohorts: Number of Participants With Study Drug-Related Dose-Limiting Toxicities (DLTs) | 1 Participants |
Primary
Doublet Cohort: Objective Response Rate (ORR)
ORR was defined as the percentage of participants with a confirmed complete response (CR) or partial response (PR) as best overall response (BOR) per response evaluation criteria in solid tumors (RECIST) version (v) 1.1. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 millimeter (mm). PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Time frame: Tumor assessments performed at baseline, then every 6 weeks for first 24 weeks, and every 9 weeks thereafter, approximately 158.4 weeks
Population: All-treated population included all participants assigned to study treatment and who actually received at least 1 dose of study treatment. Data is reported for Part A (doublet cohort) at both tusamitamab ravtansine doses.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tusamitamab Ravtansine 150 mg/m^2 + Pembrolizumab | Doublet Cohort: Objective Response Rate (ORR) | 47.8 percentage of participants |
| Tusamitamab Ravtansine 170 mg/m^2 + Pembrolizumab | Doublet Cohort: Objective Response Rate (ORR) | 0 percentage of participants |
Primary
Quadruplet Cohort: Objective Response Rate
ORR was defined as the percentage of participants with a confirmed CR or PR as per RECIST v1.1. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Time frame: Tumor assessments performed at baseline, then every 6 weeks for first 24 weeks, and every 9 weeks thereafter, approximately 139.9 weeks
Population: All-treated population included all participants assigned to study treatment and who actually received at least 1 dose of study treatment. Data is reported for Part C (quadruplet cohort) at both tusamitamab ravtansine doses.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tusamitamab Ravtansine 150 mg/m^2 + Pembrolizumab | Quadruplet Cohort: Objective Response Rate | 59.1 percentage of participants |
| Tusamitamab Ravtansine 170 mg/m^2 + Pembrolizumab | Quadruplet Cohort: Objective Response Rate | 66.7 percentage of participants |
Secondary
All Cohorts: Ctrough of Pembrolizumab
Blood samples were collected for the measurement of pembrolizumab concentrations.
Time frame: Pre-dose on Day 1 of Cycle 2 (cycle duration=3 weeks)
Population: PK population included all participants from the all-treated population with at least 1 post-baseline PK concentration with adequate documentation of dosing and sampling dates and times. Only those participants with data collected at the specified timepoint are reported. Data is reported for Part A (doublet cohort), Part B (triplet cohort) and Part C (quadruplet cohort) at both tusamitamab ravtansine doses.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tusamitamab Ravtansine 150 mg/m^2 + Pembrolizumab | All Cohorts: Ctrough of Pembrolizumab | 14.0 mcg/mL | Standard Deviation 2.2 |
| Tusamitamab Ravtansine 170 mg/m^2 + Pembrolizumab | All Cohorts: Ctrough of Pembrolizumab | 16.9 mcg/mL | Standard Deviation 4.8 |
| Tusamitamab Ravtansine 150 mg/m^2 + Pembrolizumab + Cisplatin/Carboplatin | All Cohorts: Ctrough of Pembrolizumab | 13.4 mcg/mL | Standard Deviation 5.7 |
| Tusamitamab Ravtansine 170 mg/m^2 + Pembrolizumab + Cisplatin/Carboplatin | All Cohorts: Ctrough of Pembrolizumab | 14.1 mcg/mL | — |
| Tusamitamab Ravtansine 150 mg/m^2 + Pembrolizumab + Cisplatin/Carboplatin + Pemetrexed | All Cohorts: Ctrough of Pembrolizumab | 13.2 mcg/mL | Standard Deviation 4.2 |
| Tusamitamab Ravtansine 170 mg/m^2 + Pembrolizumab + Cisplatin/Carboplatin + Pemetrexed | All Cohorts: Ctrough of Pembrolizumab | 10.3 mcg/mL | Standard Deviation 1.3 |
Secondary
All Cohorts: Disease Control Rate (DCR)
DCR was defined as percentage of participants with a confirmed CR, confirmed PR or stable disease (SD) as BOR per RECIST v1.1. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD was defined as neither sufficient shrinkage from the baseline study to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (including the baseline sum if that was the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Appearance of 1 or more new lesions was also considered progression.
Time frame: Tumor assessments performed at baseline, then every 6 weeks for first 24 weeks, and every 9 weeks thereafter, approximately 158.4 weeks (doublet), 113 weeks (triplet), and 139.9 weeks (quadruplet)
Population: All-treated population included all participants assigned to study treatment and who actually received at least 1 dose of study treatment. Data is reported for Part A (doublet cohort), Part B (triplet cohort) and Part C (quadruplet cohort) at both tusamitamab ravtansine doses.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tusamitamab Ravtansine 150 mg/m^2 + Pembrolizumab | All Cohorts: Disease Control Rate (DCR) | 82.6 percentage of participants |
| Tusamitamab Ravtansine 170 mg/m^2 + Pembrolizumab | All Cohorts: Disease Control Rate (DCR) | 100 percentage of participants |
| Tusamitamab Ravtansine 150 mg/m^2 + Pembrolizumab + Cisplatin/Carboplatin | All Cohorts: Disease Control Rate (DCR) | 100 percentage of participants |
| Tusamitamab Ravtansine 170 mg/m^2 + Pembrolizumab + Cisplatin/Carboplatin | All Cohorts: Disease Control Rate (DCR) | 100 percentage of participants |
| Tusamitamab Ravtansine 150 mg/m^2 + Pembrolizumab + Cisplatin/Carboplatin + Pemetrexed | All Cohorts: Disease Control Rate (DCR) | 81.8 percentage of participants |
| Tusamitamab Ravtansine 170 mg/m^2 + Pembrolizumab + Cisplatin/Carboplatin + Pemetrexed | All Cohorts: Disease Control Rate (DCR) | 100 percentage of participants |
Secondary
All Cohorts: Duration of Response (DOR)
DOR was defined as the time from first documented evidence of CR or PR until PD determined per RECIST v1.1 or death from any cause, whichever occurred first. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (including the baseline sum if that was the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Appearance of 1 or more new lesions was also considered progression.
Time frame: Tumor assessments performed at baseline, then every 6 weeks for first 24 weeks, and every 9 weeks thereafter, approximately 158.4 weeks (doublet), 113 weeks (triplet), and 139.9 weeks (quadruplet)
Population: All-treated population included all participants assigned to study treatment and who actually received at least 1 dose of study treatment. Only participants with confirmed CR or PR as BOR were included in the analysis. Data is reported for Part A (doublet cohort), Part B (triplet cohort) and Part C (quadruplet cohort) at both tusamitamab ravtansine doses.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tusamitamab Ravtansine 150 mg/m^2 + Pembrolizumab | All Cohorts: Duration of Response (DOR) | NA months |
| Tusamitamab Ravtansine 150 mg/m^2 + Pembrolizumab + Cisplatin/Carboplatin | All Cohorts: Duration of Response (DOR) | 10.45 months |
| Tusamitamab Ravtansine 150 mg/m^2 + Pembrolizumab + Cisplatin/Carboplatin + Pemetrexed | All Cohorts: Duration of Response (DOR) | 12.02 months |
| Tusamitamab Ravtansine 170 mg/m^2 + Pembrolizumab + Cisplatin/Carboplatin + Pemetrexed | All Cohorts: Duration of Response (DOR) | NA months |
Secondary
All Cohorts: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)
An AE was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. A serious AE was defined as any untoward medical occurrence that, at any dose resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent disability/incapacity or was a congenital anomaly/birth defect. A TEAE was defined as an AE that developed, worsened or became serious during the treatment-emergent period.
Time frame: From first dose of study treatment (Day 1) up to 30 days post last dose of study treatment, approximately 162.4 weeks (doublet), 117 weeks (triplet), and 143.9 weeks (quadruplet)
Population: All-treated population included all participants assigned to study treatment and who actually received at least 1 dose of study treatment. Data is reported for Part A (doublet cohort), Part B (triplet cohort) and Part C (quadruplet cohort) at both tusamitamab ravtansine doses.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Tusamitamab Ravtansine 150 mg/m^2 + Pembrolizumab | All Cohorts: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) | Any TEAE | 23 Participants |
| Tusamitamab Ravtansine 150 mg/m^2 + Pembrolizumab | All Cohorts: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) | Any TESAE | 9 Participants |
| Tusamitamab Ravtansine 170 mg/m^2 + Pembrolizumab | All Cohorts: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) | Any TEAE | 2 Participants |
| Tusamitamab Ravtansine 170 mg/m^2 + Pembrolizumab | All Cohorts: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) | Any TESAE | 0 Participants |
| Tusamitamab Ravtansine 150 mg/m^2 + Pembrolizumab + Cisplatin/Carboplatin | All Cohorts: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) | Any TEAE | 6 Participants |
| Tusamitamab Ravtansine 150 mg/m^2 + Pembrolizumab + Cisplatin/Carboplatin | All Cohorts: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) | Any TESAE | 1 Participants |
| Tusamitamab Ravtansine 170 mg/m^2 + Pembrolizumab + Cisplatin/Carboplatin | All Cohorts: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) | Any TEAE | 1 Participants |
| Tusamitamab Ravtansine 170 mg/m^2 + Pembrolizumab + Cisplatin/Carboplatin | All Cohorts: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) | Any TESAE | 1 Participants |
| Tusamitamab Ravtansine 150 mg/m^2 + Pembrolizumab + Cisplatin/Carboplatin + Pemetrexed | All Cohorts: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) | Any TEAE | 22 Participants |
| Tusamitamab Ravtansine 150 mg/m^2 + Pembrolizumab + Cisplatin/Carboplatin + Pemetrexed | All Cohorts: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) | Any TESAE | 11 Participants |
| Tusamitamab Ravtansine 170 mg/m^2 + Pembrolizumab + Cisplatin/Carboplatin + Pemetrexed | All Cohorts: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) | Any TEAE | 3 Participants |
| Tusamitamab Ravtansine 170 mg/m^2 + Pembrolizumab + Cisplatin/Carboplatin + Pemetrexed | All Cohorts: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) | Any TESAE | 2 Participants |
Secondary
All Cohorts: Number of Participants With Treatment-emergent Anti-Therapeutic Antibodies (ATAs) Against Tusamitamab Ravtansine
Blood samples were collected to assess the presence of treatment-emergent ATA against tusamitamab ravtansine. ATA incidence was defined as the number of participants found to have treatment-emergent ATA response during the study.
Time frame: From first dose of study treatment (Day 1) up to 30 days post last dose of study treatment, approximately 162.4 weeks (doublet), 117 weeks (triplet), and 143.9 weeks (quadruplet)
Population: ATA population included all participants from the all-treated population with at least 1 post-baseline ATA result (negative, positive, or inconclusive). Data is reported for Part A (doublet cohort), Part B (triplet cohort) and Part C (quadruplet cohort) at both tusamitamab ravtansine doses.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Tusamitamab Ravtansine 150 mg/m^2 + Pembrolizumab | All Cohorts: Number of Participants With Treatment-emergent Anti-Therapeutic Antibodies (ATAs) Against Tusamitamab Ravtansine | 9 Participants |
| Tusamitamab Ravtansine 170 mg/m^2 + Pembrolizumab | All Cohorts: Number of Participants With Treatment-emergent Anti-Therapeutic Antibodies (ATAs) Against Tusamitamab Ravtansine | 1 Participants |
| Tusamitamab Ravtansine 150 mg/m^2 + Pembrolizumab + Cisplatin/Carboplatin | All Cohorts: Number of Participants With Treatment-emergent Anti-Therapeutic Antibodies (ATAs) Against Tusamitamab Ravtansine | 3 Participants |
| Tusamitamab Ravtansine 170 mg/m^2 + Pembrolizumab + Cisplatin/Carboplatin | All Cohorts: Number of Participants With Treatment-emergent Anti-Therapeutic Antibodies (ATAs) Against Tusamitamab Ravtansine | 0 Participants |
| Tusamitamab Ravtansine 150 mg/m^2 + Pembrolizumab + Cisplatin/Carboplatin + Pemetrexed | All Cohorts: Number of Participants With Treatment-emergent Anti-Therapeutic Antibodies (ATAs) Against Tusamitamab Ravtansine | 8 Participants |
| Tusamitamab Ravtansine 170 mg/m^2 + Pembrolizumab + Cisplatin/Carboplatin + Pemetrexed | All Cohorts: Number of Participants With Treatment-emergent Anti-Therapeutic Antibodies (ATAs) Against Tusamitamab Ravtansine | 2 Participants |
Secondary
All Cohorts: Trough Concentration (Ctrough) of Tusamitamab Ravtansine
Blood samples were collected for the measurement of tusamitamab ravtansine concentrations.
Time frame: Pre-dose on Day 1 of Cycle 2 (cycle duration=3 weeks)
Population: PK population included all participants from the all-treated population with at least 1 post-baseline PK concentration with adequate documentation of dosing and sampling dates and times. Only those participants with data collected at the specified timepoint are reported. Data is reported for Part A (doublet cohort), Part B (triplet cohort) and Part C (quadruplet cohort) at both tusamitamab ravtansine doses.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tusamitamab Ravtansine 150 mg/m^2 + Pembrolizumab | All Cohorts: Trough Concentration (Ctrough) of Tusamitamab Ravtansine | 8.0 microgram per milliliter (mcg/mL) | Standard Deviation 3.5 |
| Tusamitamab Ravtansine 170 mg/m^2 + Pembrolizumab | All Cohorts: Trough Concentration (Ctrough) of Tusamitamab Ravtansine | 11.7 microgram per milliliter (mcg/mL) | Standard Deviation 1.5 |
| Tusamitamab Ravtansine 150 mg/m^2 + Pembrolizumab + Cisplatin/Carboplatin | All Cohorts: Trough Concentration (Ctrough) of Tusamitamab Ravtansine | 7.6 microgram per milliliter (mcg/mL) | Standard Deviation 8 |
| Tusamitamab Ravtansine 170 mg/m^2 + Pembrolizumab + Cisplatin/Carboplatin | All Cohorts: Trough Concentration (Ctrough) of Tusamitamab Ravtansine | 0.0 microgram per milliliter (mcg/mL) | — |
| Tusamitamab Ravtansine 150 mg/m^2 + Pembrolizumab + Cisplatin/Carboplatin + Pemetrexed | All Cohorts: Trough Concentration (Ctrough) of Tusamitamab Ravtansine | 4.8 microgram per milliliter (mcg/mL) | Standard Deviation 2.7 |
| Tusamitamab Ravtansine 170 mg/m^2 + Pembrolizumab + Cisplatin/Carboplatin + Pemetrexed | All Cohorts: Trough Concentration (Ctrough) of Tusamitamab Ravtansine | 7.6 microgram per milliliter (mcg/mL) | Standard Deviation 0.9 |
Secondary
Doublet and Quadruplet Cohorts: Progression-free Survival (PFS)
PFS was defined as the time from the first study treatment administration to the date of the first documented progressive disease (PD) or death due to any cause, whichever came first. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (including the baseline sum if that was the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Appearance of 1 or more new lesions was also considered progression.
Time frame: Tumor assessments performed at baseline, then every 6 weeks for first 24 weeks, and every 9 weeks thereafter, approximately 158.4 weeks (doublet) and 139.9 weeks (quadruplet)
Population: All-treated population included all participants assigned to study treatment and who actually received at least 1 dose of study treatment. Data is reported for Part A (doublet cohort) and Part C (quadruplet cohort) at both tusamitamab ravtansine doses.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tusamitamab Ravtansine 150 mg/m^2 + Pembrolizumab | Doublet and Quadruplet Cohorts: Progression-free Survival (PFS) | 28.45 months |
| Tusamitamab Ravtansine 170 mg/m^2 + Pembrolizumab | Doublet and Quadruplet Cohorts: Progression-free Survival (PFS) | NA months |
| Tusamitamab Ravtansine 150 mg/m^2 + Pembrolizumab + Cisplatin/Carboplatin | Doublet and Quadruplet Cohorts: Progression-free Survival (PFS) | 11.56 months |
| Tusamitamab Ravtansine 170 mg/m^2 + Pembrolizumab + Cisplatin/Carboplatin | Doublet and Quadruplet Cohorts: Progression-free Survival (PFS) | NA months |
Secondary
Quadruplet Cohort: Plasma Concentration of Pemetrexed
Blood samples were collected for the measurement of pemetrexed concentrations.
Time frame: 30 minutes post-dose on Day 1 of Cycle 1 (cycle duration=3 weeks)
Population: PK population included all participants from the all-treated population with at least 1 post-baseline PK concentration with adequate documentation of dosing and sampling dates and times. Only those participants with data collected at the specified timepoint are reported. Data is reported for Part C (quadruplet cohort) at both tusamitamab ravtansine doses.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tusamitamab Ravtansine 150 mg/m^2 + Pembrolizumab | Quadruplet Cohort: Plasma Concentration of Pemetrexed | 68.5 mcg/mL | Standard Deviation 80.8 |
| Tusamitamab Ravtansine 170 mg/m^2 + Pembrolizumab | Quadruplet Cohort: Plasma Concentration of Pemetrexed | 53.6 mcg/mL | Standard Deviation 48.3 |
Secondary
Triplet and Quadruplet Cohorts: Total Plasma Concentration Observed at the End of Infusion (Ceoi) of Cisplatin
Blood samples were collected for the measurement of cisplatin concentrations.
Time frame: At end of infusion on Day 1 of Cycle 1 (cycle duration=3 weeks)
Population: PK population included all participants from the all-treated population with at least 1 post-baseline PK concentration with adequate documentation of dosing and sampling dates and times. Only those participants with data collected at the specified timepoint are reported. Data is reported for Part B (triplet cohort) and Part C (quadruplet cohort) at both tusamitamab ravtansine doses.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tusamitamab Ravtansine 150 mg/m^2 + Pembrolizumab | Triplet and Quadruplet Cohorts: Total Plasma Concentration Observed at the End of Infusion (Ceoi) of Cisplatin | 3.3 mcg/mL | — |
| Tusamitamab Ravtansine 150 mg/m^2 + Pembrolizumab + Cisplatin/Carboplatin | Triplet and Quadruplet Cohorts: Total Plasma Concentration Observed at the End of Infusion (Ceoi) of Cisplatin | 3.9 mcg/mL | Standard Deviation 1 |
Secondary
Triplet and Quadruplet Cohorts: Total Plasma Concentration Observed at the End of Infusion of Carboplatin
Blood samples were collected for the measurement of carboplatin concentrations.
Time frame: At end of infusion on Day 1 of Cycle 1 (cycle duration=3 weeks)
Population: PK population included all participants from the all-treated population with at least 1 post-baseline PK concentration with adequate documentation of dosing and sampling dates and times. Only those participants with data collected at the specified timepoint are reported. Data is reported for Part B (triplet cohort) and Part C (quadruplet cohort) at both tusamitamab ravtansine doses.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tusamitamab Ravtansine 150 mg/m^2 + Pembrolizumab | Triplet and Quadruplet Cohorts: Total Plasma Concentration Observed at the End of Infusion of Carboplatin | 33.4 mcg/mL | Standard Deviation 5 |
| Tusamitamab Ravtansine 170 mg/m^2 + Pembrolizumab | Triplet and Quadruplet Cohorts: Total Plasma Concentration Observed at the End of Infusion of Carboplatin | 20.8 mcg/mL | — |
| Tusamitamab Ravtansine 150 mg/m^2 + Pembrolizumab + Cisplatin/Carboplatin | Triplet and Quadruplet Cohorts: Total Plasma Concentration Observed at the End of Infusion of Carboplatin | 36.7 mcg/mL | Standard Deviation 17.4 |
| Tusamitamab Ravtansine 170 mg/m^2 + Pembrolizumab + Cisplatin/Carboplatin | Triplet and Quadruplet Cohorts: Total Plasma Concentration Observed at the End of Infusion of Carboplatin | 29.7 mcg/mL | Standard Deviation 1.5 |
Secondary
Triplet Cohort: Objective Response Rate
ORR was defined as the percentage of participants with a confirmed CR or PR as per RECIST v1.1. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Time frame: Tumor assessments performed at baseline, then every 6 weeks for first 24 weeks, and every 9 weeks thereafter, approximately 113 weeks
Population: All-treated population included all participants assigned to study treatment and who actually received at least 1 dose of study treatment. Data is reported for Part B (triplet cohort) at both tusamitamab ravtansine doses.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tusamitamab Ravtansine 150 mg/m^2 + Pembrolizumab | Triplet Cohort: Objective Response Rate | 66.7 percentage of participants |
| Tusamitamab Ravtansine 170 mg/m^2 + Pembrolizumab | Triplet Cohort: Objective Response Rate | 0 percentage of participants |