Lung Cancer
Conditions
Brief summary
A study to evaluate the safety of Nivolumab given in combination with Ipilimumab in patients with advanced cancers. The initial group will enroll patients with newly diagnosed Stage 4 or non-small cell lung cancer that has come back.
Interventions
DRUGNivolumab in combination with Ipilimumab
Specified dose on specified days
Sponsors
Bristol-Myers Squibb
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
* Histologically confirmed Stage 4 or recurrent non-small cell lung cancer * Eastern Cooperative Oncology Group (ECOG) score 0-1 (Physically able to carry out light housework or office work through to being fully active as you were before cancer) * No prior systemic anticancer therapy (including EGFR and ALK inhibitors) * Tissue or Programmed death-ligand 1 (PD-L1) results available Cohort 1A Inclusion Criteria: * Eastern Cooperative Oncology Group (ECOG) score 2 or * Eastern Cooperative Oncology Group (ECOG) score 0-1 and one disease specific criteria as listed in the protocol Cohort C Inclusion Criteria: * High Tumor Mutation Burden
Exclusion criteria
* Untreated brain metastases * An active malignancy that requires concurrent intervention * Active, known or suspected autoimmune disease * Carcinomatous meningitis, which means there is inflammation of the covering of the brain, caused by cancer Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With High Grade (Grade 3-4 and Grade 5) Drug-Related Select Adverse Events (AEs) | From first dose to 30 days post last dose (Up to approximately 27 months) | Drug related AEs are those events with relationship to study drug. If the relationship to study drug is missing, the AE will be considered as drug-related. The select AEs of interest are the following: Pulmonary, Renal, Gastrointestinal, Hepatic, Skin, Endocrine, and hypersensitivity/infusion reaction events. AEs are reported using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4. Grade 3= Prolonged severe reaction Grade 4= Life threatening Grade 5= Death |
| Number of Participants With High Grade (Grade 3-4 and Grade 5) Immune-Mediated Adverse Events (imAEs) | From first dose to 100 days post last dose (Up to approximately 29 months) | imAEs are specific events that include pneumonitis, diarrhea/colitis, hepatitis, nephritis/renal dysfunction, rash, and endocrine (adrenal insufficiency, hypothyroidism/thyroiditis, hyperthyroidism, diabetes mellitus, and hypophysitis). AEs are reported using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4. Grade 3= Prolonged severe reaction Grade 4= Life threatening Grade 5= Death |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | From first dosing date up to approximately 67 months | ORR is defined as the percentage of participants with a best overall response of confirmed complete response (CR) or partial response (PR). CR= Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. PR= ≥ 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. |
| Progression Free Survival (PFS) | From first dosing date to the date of first documented tumor progression or, death due to any cause, whichever occurs first (Up to approximately 67 months) | PFS is defined as the time from first dosing date to the date of the first documented tumor progression, as determined by investigators (per RECIST v1.1), or death due to any cause, whichever occurs first. Progressive Disease (PD)= ≥ 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study. The sum must also demonstrate an absolute increase of ≥ 5 mm. The appearance of one or more new lesions is also considered progression. |
| Change From Baseline in Health-Related Quality of Life (HRQoL) Using Functional Assessment of Cancer Therapy-Lung (FACT-L) | From baseline and up to subsequent survival follow-up visit 18 (Up to approximately 67 months) | FACT-L is a quality-of-life questionnaire which includes Lung Cancer Subscale (LCS) that assesses the treatment impact on lung cancer related symptoms in 5 domains: Physical, social/family, emotional, and functional well-being using a 5-point scale (0=not at all; 1=a little bit, 2=somewhat; 3=quite a bit; 4=very much) added to obtain total score. The ranges of possible total scores are 0-136 for the FACT-L with a higher score representing better quality of life, improved symptomatology and enhanced physical/functional outcomes. According to Functional Assessment of Chronic Illness Therapy scoring guidelines, in the event of missing responses for some of the questions, scores will be prorated using the average of the other answers in that scale. Baseline is defined as events that occur before the date/time of first dose. Post treatment visits include follow-up (FU) visit 1, FU visit 2, and subsequent survival FU visits to occur every 3 months up until survival FU visit 18. |
| Duration of Response (DoR) | From first dosing date to the date of first documented tumor progression or, death due to any cause, whichever occurs first (Up to approximately 67 months) | DoR is defined as the time between the date of first confirmed complete response (CR) or partial response (PR) to the date of the first documented tumor progression per RECIST 1.1, or death due to any cause, whichever occurs first. CR= Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. PR= ≥ 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive Disease (PD)= ≥ 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study. The sum must also demonstrate an absolute increase of ≥ 5 mm. The appearance of one or more new lesions is also considered progression. |
| Overall Survival (OS) | From first dosing date to the date of death (Up to approximately 67 months) | OS is defined as the time from first dosing date to the date of death. A participant who has not died will be censored at last known date alive. |
Countries
Argentina, Belgium, Brazil, Canada, Chile, Czechia, France, Germany, Greece, Hungary, Italy, Mexico, Netherlands, Poland, Romania, Russia, Spain, Switzerland, Turkey (Türkiye), United Kingdom, United States
Participant flow
Pre-assignment details
Analysis for the NSCLC special population cohort A1 is pre-specified as exploratory.
Participants by arm
| Arm | Count |
|---|---|
| Cohort A First-line NSCLC: Nivolumab 240 mg IV Q2W + Ipilimumab 1 mg/kg IV Q6W, starting on Day 1, until progression, unacceptable toxicity, withdrawal of consent, 24 months of treatment from the first dose, or the study ends, whichever occurs first | 391 |
| Cohort A1 First-line NSCLC special population: Nivolumab 240 mg IV Q2W + Ipilimumab 1 mg/kg IV Q6W, starting on Day 1, until progression, unacceptable toxicity, withdrawal of consent, 24 months of treatment from the first dose, or the study ends, whichever occurs first | 198 |
| Cohort B Second-line NSCLC: Nivolumab 240 mg IV Q2W + Ipilimumab 1 mg/kg IV Q6W, starting on Day 1, until progression, unacceptable toxicity, withdrawal of consent, 24 months of treatment from the first dose, or the study ends, whichever occurs first | 395 |
| Cohort C First-line NSCLC high tumor mutational burden (H-TMB \>= 10 mutations/MB): Nivolumab 240 mg IV Q2W + Ipilimumab 1 mg/kg IV Q6W, starting on Day 1, until progression, unacceptable toxicity, withdrawal of consent, 24 months of treatment from the first dose, or the study ends, whichever occurs first | 57 |
| Total | 1,041 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Administrative reason by sponsor | 0 | 0 | 1 | 0 |
| Overall Study | Adverse Event unrelated to study drug | 30 | 18 | 21 | 6 |
| Overall Study | Death | 7 | 3 | 5 | 1 |
| Overall Study | Disease progression | 184 | 109 | 260 | 19 |
| Overall Study | Lost to Follow-up | 0 | 0 | 2 | 0 |
| Overall Study | Maximum clinical benefit | 5 | 2 | 1 | 0 |
| Overall Study | Other reasons | 4 | 8 | 6 | 0 |
| Overall Study | Participant no longer meets study criteria | 0 | 1 | 1 | 0 |
| Overall Study | Participant request to discontinue study treatment | 10 | 5 | 5 | 3 |
| Overall Study | Poor/Non-compliance | 0 | 2 | 1 | 0 |
| Overall Study | Study drug toxicity | 90 | 32 | 55 | 14 |
| Overall Study | Withdrawal by Subject | 5 | 2 | 7 | 2 |
Baseline characteristics
| Characteristic | Total | Cohort A | Cohort A1 | Cohort B | Cohort C |
|---|---|---|---|---|---|
| Age, Customized >= 65 and < 85 years old | 546 Participants | 206 Participants | 115 Participants | 195 Participants | 30 Participants |
| Age, Customized < 65 years old | 488 Participants | 183 Participants | 81 Participants | 200 Participants | 24 Participants |
| Age, Customized >= 85 years old | 7 Participants | 2 Participants | 2 Participants | 0 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 38 Participants | 10 Participants | 13 Participants | 12 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 492 Participants | 185 Participants | 78 Participants | 175 Participants | 54 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 511 Participants | 196 Participants | 107 Participants | 208 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 7 Participants | 3 Participants | 0 Participants | 4 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 22 Participants | 6 Participants | 3 Participants | 5 Participants | 8 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 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 | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 10 Participants | 3 Participants | 1 Participants | 4 Participants | 2 Participants |
| Race (NIH/OMB) White | 1002 Participants | 379 Participants | 194 Participants | 382 Participants | 47 Participants |
| Sex: Female, Male Female | 383 Participants | 155 Participants | 71 Participants | 128 Participants | 29 Participants |
| Sex: Female, Male Male | 658 Participants | 236 Participants | 127 Participants | 267 Participants | 28 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 294 / 391 | 166 / 198 | 334 / 395 | 32 / 57 |
| other Total, other adverse events | 362 / 391 | 174 / 198 | 346 / 395 | 56 / 57 |
| serious Total, serious adverse events | 264 / 391 | 149 / 198 | 282 / 395 | 42 / 57 |
Outcome results
Primary
Number of Participants With High Grade (Grade 3-4 and Grade 5) Drug-Related Select Adverse Events (AEs)
Drug related AEs are those events with relationship to study drug. If the relationship to study drug is missing, the AE will be considered as drug-related. The select AEs of interest are the following: Pulmonary, Renal, Gastrointestinal, Hepatic, Skin, Endocrine, and hypersensitivity/infusion reaction events. AEs are reported using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4. Grade 3= Prolonged severe reaction Grade 4= Life threatening Grade 5= Death
Time frame: From first dose to 30 days post last dose (Up to approximately 27 months)
Population: All treated participants as pre-specified in Cohort A, B, and C
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort A | Number of Participants With High Grade (Grade 3-4 and Grade 5) Drug-Related Select Adverse Events (AEs) | Skin AEs grade 5 | 0 Participants |
| Cohort A | Number of Participants With High Grade (Grade 3-4 and Grade 5) Drug-Related Select Adverse Events (AEs) | Pulmonary AEs grade 5 | 0 Participants |
| Cohort A | Number of Participants With High Grade (Grade 3-4 and Grade 5) Drug-Related Select Adverse Events (AEs) | Hypersensitivity/Infusion Reaction grade 3-4 | 6 Participants |
| Cohort A | Number of Participants With High Grade (Grade 3-4 and Grade 5) Drug-Related Select Adverse Events (AEs) | Renal AEs grade 3-4 | 2 Participants |
| Cohort A | Number of Participants With High Grade (Grade 3-4 and Grade 5) Drug-Related Select Adverse Events (AEs) | Hepatic AEs grade 3-4 | 25 Participants |
| Cohort A | Number of Participants With High Grade (Grade 3-4 and Grade 5) Drug-Related Select Adverse Events (AEs) | Skin AEs grade 3-4 | 14 Participants |
| Cohort A | Number of Participants With High Grade (Grade 3-4 and Grade 5) Drug-Related Select Adverse Events (AEs) | Renal AEs grade 5 | 0 Participants |
| Cohort A | Number of Participants With High Grade (Grade 3-4 and Grade 5) Drug-Related Select Adverse Events (AEs) | Gastrointestinal AEs grade 5 | 0 Participants |
| Cohort A | Number of Participants With High Grade (Grade 3-4 and Grade 5) Drug-Related Select Adverse Events (AEs) | Endocrine AEs grade 5 | 0 Participants |
| Cohort A | Number of Participants With High Grade (Grade 3-4 and Grade 5) Drug-Related Select Adverse Events (AEs) | Hepatic AEs grade 5 | 0 Participants |
| Cohort A | Number of Participants With High Grade (Grade 3-4 and Grade 5) Drug-Related Select Adverse Events (AEs) | Gastrointestinal AEs grade 3-4 | 19 Participants |
| Cohort A | Number of Participants With High Grade (Grade 3-4 and Grade 5) Drug-Related Select Adverse Events (AEs) | Endocrine AEs grade 3-4 | 16 Participants |
| Cohort A | Number of Participants With High Grade (Grade 3-4 and Grade 5) Drug-Related Select Adverse Events (AEs) | Pulmonary AEs grade 3-4 | 18 Participants |
| Cohort A | Number of Participants With High Grade (Grade 3-4 and Grade 5) Drug-Related Select Adverse Events (AEs) | Hypersensitivity/Infusion Reaction grade 5 | 0 Participants |
| Cohort B | Number of Participants With High Grade (Grade 3-4 and Grade 5) Drug-Related Select Adverse Events (AEs) | Hepatic AEs grade 5 | 0 Participants |
| Cohort B | Number of Participants With High Grade (Grade 3-4 and Grade 5) Drug-Related Select Adverse Events (AEs) | Gastrointestinal AEs grade 3-4 | 15 Participants |
| Cohort B | Number of Participants With High Grade (Grade 3-4 and Grade 5) Drug-Related Select Adverse Events (AEs) | Gastrointestinal AEs grade 5 | 0 Participants |
| Cohort B | Number of Participants With High Grade (Grade 3-4 and Grade 5) Drug-Related Select Adverse Events (AEs) | Hepatic AEs grade 3-4 | 17 Participants |
| Cohort B | Number of Participants With High Grade (Grade 3-4 and Grade 5) Drug-Related Select Adverse Events (AEs) | Pulmonary AEs grade 3-4 | 11 Participants |
| Cohort B | Number of Participants With High Grade (Grade 3-4 and Grade 5) Drug-Related Select Adverse Events (AEs) | Pulmonary AEs grade 5 | 1 Participants |
| Cohort B | Number of Participants With High Grade (Grade 3-4 and Grade 5) Drug-Related Select Adverse Events (AEs) | Renal AEs grade 3-4 | 1 Participants |
| Cohort B | Number of Participants With High Grade (Grade 3-4 and Grade 5) Drug-Related Select Adverse Events (AEs) | Renal AEs grade 5 | 0 Participants |
| Cohort B | Number of Participants With High Grade (Grade 3-4 and Grade 5) Drug-Related Select Adverse Events (AEs) | Skin AEs grade 3-4 | 9 Participants |
| Cohort B | Number of Participants With High Grade (Grade 3-4 and Grade 5) Drug-Related Select Adverse Events (AEs) | Skin AEs grade 5 | 0 Participants |
| Cohort B | Number of Participants With High Grade (Grade 3-4 and Grade 5) Drug-Related Select Adverse Events (AEs) | Endocrine AEs grade 3-4 | 11 Participants |
| Cohort B | Number of Participants With High Grade (Grade 3-4 and Grade 5) Drug-Related Select Adverse Events (AEs) | Hypersensitivity/Infusion Reaction grade 3-4 | 3 Participants |
| Cohort B | Number of Participants With High Grade (Grade 3-4 and Grade 5) Drug-Related Select Adverse Events (AEs) | Hypersensitivity/Infusion Reaction grade 5 | 0 Participants |
| Cohort B | Number of Participants With High Grade (Grade 3-4 and Grade 5) Drug-Related Select Adverse Events (AEs) | Endocrine AEs grade 5 | 0 Participants |
| Cohort C | Number of Participants With High Grade (Grade 3-4 and Grade 5) Drug-Related Select Adverse Events (AEs) | Skin AEs grade 5 | 0 Participants |
| Cohort C | Number of Participants With High Grade (Grade 3-4 and Grade 5) Drug-Related Select Adverse Events (AEs) | Hepatic AEs grade 5 | 0 Participants |
| Cohort C | Number of Participants With High Grade (Grade 3-4 and Grade 5) Drug-Related Select Adverse Events (AEs) | Pulmonary AEs grade 5 | 0 Participants |
| Cohort C | Number of Participants With High Grade (Grade 3-4 and Grade 5) Drug-Related Select Adverse Events (AEs) | Endocrine AEs grade 3-4 | 2 Participants |
| Cohort C | Number of Participants With High Grade (Grade 3-4 and Grade 5) Drug-Related Select Adverse Events (AEs) | Hepatic AEs grade 3-4 | 3 Participants |
| Cohort C | Number of Participants With High Grade (Grade 3-4 and Grade 5) Drug-Related Select Adverse Events (AEs) | Endocrine AEs grade 5 | 0 Participants |
| Cohort C | Number of Participants With High Grade (Grade 3-4 and Grade 5) Drug-Related Select Adverse Events (AEs) | Gastrointestinal AEs grade 5 | 0 Participants |
| Cohort C | Number of Participants With High Grade (Grade 3-4 and Grade 5) Drug-Related Select Adverse Events (AEs) | Hypersensitivity/Infusion Reaction grade 5 | 0 Participants |
| Cohort C | Number of Participants With High Grade (Grade 3-4 and Grade 5) Drug-Related Select Adverse Events (AEs) | Renal AEs grade 5 | 0 Participants |
| Cohort C | Number of Participants With High Grade (Grade 3-4 and Grade 5) Drug-Related Select Adverse Events (AEs) | Renal AEs grade 3-4 | 1 Participants |
| Cohort C | Number of Participants With High Grade (Grade 3-4 and Grade 5) Drug-Related Select Adverse Events (AEs) | Hypersensitivity/Infusion Reaction grade 3-4 | 0 Participants |
| Cohort C | Number of Participants With High Grade (Grade 3-4 and Grade 5) Drug-Related Select Adverse Events (AEs) | Skin AEs grade 3-4 | 2 Participants |
| Cohort C | Number of Participants With High Grade (Grade 3-4 and Grade 5) Drug-Related Select Adverse Events (AEs) | Pulmonary AEs grade 3-4 | 2 Participants |
| Cohort C | Number of Participants With High Grade (Grade 3-4 and Grade 5) Drug-Related Select Adverse Events (AEs) | Gastrointestinal AEs grade 3-4 | 4 Participants |
Primary
Number of Participants With High Grade (Grade 3-4 and Grade 5) Immune-Mediated Adverse Events (imAEs)
imAEs are specific events that include pneumonitis, diarrhea/colitis, hepatitis, nephritis/renal dysfunction, rash, and endocrine (adrenal insufficiency, hypothyroidism/thyroiditis, hyperthyroidism, diabetes mellitus, and hypophysitis). AEs are reported using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4. Grade 3= Prolonged severe reaction Grade 4= Life threatening Grade 5= Death
Time frame: From first dose to 100 days post last dose (Up to approximately 29 months)
Population: All treated participants as pre-specified in Cohort A, B, and C
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort A | Number of Participants With High Grade (Grade 3-4 and Grade 5) Immune-Mediated Adverse Events (imAEs) | Hypersensitivity grade 3-4 | 4 Participants |
| Cohort A | Number of Participants With High Grade (Grade 3-4 and Grade 5) Immune-Mediated Adverse Events (imAEs) | Hypothyroidism grade 3-4 | 1 Participants |
| Cohort A | Number of Participants With High Grade (Grade 3-4 and Grade 5) Immune-Mediated Adverse Events (imAEs) | Hepatitis grade 3-4 | 18 Participants |
| Cohort A | Number of Participants With High Grade (Grade 3-4 and Grade 5) Immune-Mediated Adverse Events (imAEs) | Rash grade 3-4 | 14 Participants |
| Cohort A | Number of Participants With High Grade (Grade 3-4 and Grade 5) Immune-Mediated Adverse Events (imAEs) | Thyroiditis grade 3-4 | 1 Participants |
| Cohort A | Number of Participants With High Grade (Grade 3-4 and Grade 5) Immune-Mediated Adverse Events (imAEs) | Diarrhea/Colitis grade 3-4 | 19 Participants |
| Cohort A | Number of Participants With High Grade (Grade 3-4 and Grade 5) Immune-Mediated Adverse Events (imAEs) | Nephritis and Renal Dysfunction grade 3-4 | 2 Participants |
| Cohort A | Number of Participants With High Grade (Grade 3-4 and Grade 5) Immune-Mediated Adverse Events (imAEs) | Diabetes Mellitus grade 3-4 | 1 Participants |
| Cohort A | Number of Participants With High Grade (Grade 3-4 and Grade 5) Immune-Mediated Adverse Events (imAEs) | Hyperthyroidism grade 3-4 | 0 Participants |
| Cohort A | Number of Participants With High Grade (Grade 3-4 and Grade 5) Immune-Mediated Adverse Events (imAEs) | Adrenal Insufficiency grade 3-4 | 5 Participants |
| Cohort A | Number of Participants With High Grade (Grade 3-4 and Grade 5) Immune-Mediated Adverse Events (imAEs) | Any category imAEs grade 5 | 0 Participants |
| Cohort A | Number of Participants With High Grade (Grade 3-4 and Grade 5) Immune-Mediated Adverse Events (imAEs) | Pneumonitis grade 3-4 | 20 Participants |
| Cohort A | Number of Participants With High Grade (Grade 3-4 and Grade 5) Immune-Mediated Adverse Events (imAEs) | Hypothyroidism/Thyroiditis grade 3-4 | 2 Participants |
| Cohort A | Number of Participants With High Grade (Grade 3-4 and Grade 5) Immune-Mediated Adverse Events (imAEs) | Hypophysitis grade 3-4 | 3 Participants |
| Cohort B | Number of Participants With High Grade (Grade 3-4 and Grade 5) Immune-Mediated Adverse Events (imAEs) | Hypersensitivity grade 3-4 | 2 Participants |
| Cohort B | Number of Participants With High Grade (Grade 3-4 and Grade 5) Immune-Mediated Adverse Events (imAEs) | Pneumonitis grade 3-4 | 14 Participants |
| Cohort B | Number of Participants With High Grade (Grade 3-4 and Grade 5) Immune-Mediated Adverse Events (imAEs) | Diarrhea/Colitis grade 3-4 | 15 Participants |
| Cohort B | Number of Participants With High Grade (Grade 3-4 and Grade 5) Immune-Mediated Adverse Events (imAEs) | Hepatitis grade 3-4 | 13 Participants |
| Cohort B | Number of Participants With High Grade (Grade 3-4 and Grade 5) Immune-Mediated Adverse Events (imAEs) | Adrenal Insufficiency grade 3-4 | 4 Participants |
| Cohort B | Number of Participants With High Grade (Grade 3-4 and Grade 5) Immune-Mediated Adverse Events (imAEs) | Hypothyroidism/Thyroiditis grade 3-4 | 2 Participants |
| Cohort B | Number of Participants With High Grade (Grade 3-4 and Grade 5) Immune-Mediated Adverse Events (imAEs) | Hypothyroidism grade 3-4 | 1 Participants |
| Cohort B | Number of Participants With High Grade (Grade 3-4 and Grade 5) Immune-Mediated Adverse Events (imAEs) | Thyroiditis grade 3-4 | 1 Participants |
| Cohort B | Number of Participants With High Grade (Grade 3-4 and Grade 5) Immune-Mediated Adverse Events (imAEs) | Diabetes Mellitus grade 3-4 | 0 Participants |
| Cohort B | Number of Participants With High Grade (Grade 3-4 and Grade 5) Immune-Mediated Adverse Events (imAEs) | Nephritis and Renal Dysfunction grade 3-4 | 1 Participants |
| Cohort B | Number of Participants With High Grade (Grade 3-4 and Grade 5) Immune-Mediated Adverse Events (imAEs) | Rash grade 3-4 | 8 Participants |
| Cohort B | Number of Participants With High Grade (Grade 3-4 and Grade 5) Immune-Mediated Adverse Events (imAEs) | Hyperthyroidism grade 3-4 | 2 Participants |
| Cohort B | Number of Participants With High Grade (Grade 3-4 and Grade 5) Immune-Mediated Adverse Events (imAEs) | Hypophysitis grade 3-4 | 1 Participants |
| Cohort B | Number of Participants With High Grade (Grade 3-4 and Grade 5) Immune-Mediated Adverse Events (imAEs) | Any category imAEs grade 5 | 0 Participants |
| Cohort C | Number of Participants With High Grade (Grade 3-4 and Grade 5) Immune-Mediated Adverse Events (imAEs) | Hypophysitis grade 3-4 | 1 Participants |
| Cohort C | Number of Participants With High Grade (Grade 3-4 and Grade 5) Immune-Mediated Adverse Events (imAEs) | Rash grade 3-4 | 1 Participants |
| Cohort C | Number of Participants With High Grade (Grade 3-4 and Grade 5) Immune-Mediated Adverse Events (imAEs) | Hypothyroidism/Thyroiditis grade 3-4 | 0 Participants |
| Cohort C | Number of Participants With High Grade (Grade 3-4 and Grade 5) Immune-Mediated Adverse Events (imAEs) | Adrenal Insufficiency grade 3-4 | 1 Participants |
| Cohort C | Number of Participants With High Grade (Grade 3-4 and Grade 5) Immune-Mediated Adverse Events (imAEs) | Hypersensitivity grade 3-4 | 0 Participants |
| Cohort C | Number of Participants With High Grade (Grade 3-4 and Grade 5) Immune-Mediated Adverse Events (imAEs) | Hepatitis grade 3-4 | 1 Participants |
| Cohort C | Number of Participants With High Grade (Grade 3-4 and Grade 5) Immune-Mediated Adverse Events (imAEs) | Pneumonitis grade 3-4 | 3 Participants |
| Cohort C | Number of Participants With High Grade (Grade 3-4 and Grade 5) Immune-Mediated Adverse Events (imAEs) | Hyperthyroidism grade 3-4 | 0 Participants |
| Cohort C | Number of Participants With High Grade (Grade 3-4 and Grade 5) Immune-Mediated Adverse Events (imAEs) | Diarrhea/Colitis grade 3-4 | 3 Participants |
| Cohort C | Number of Participants With High Grade (Grade 3-4 and Grade 5) Immune-Mediated Adverse Events (imAEs) | Diabetes Mellitus grade 3-4 | 0 Participants |
| Cohort C | Number of Participants With High Grade (Grade 3-4 and Grade 5) Immune-Mediated Adverse Events (imAEs) | Thyroiditis grade 3-4 | 0 Participants |
| Cohort C | Number of Participants With High Grade (Grade 3-4 and Grade 5) Immune-Mediated Adverse Events (imAEs) | Any category imAEs grade 5 | 0 Participants |
| Cohort C | Number of Participants With High Grade (Grade 3-4 and Grade 5) Immune-Mediated Adverse Events (imAEs) | Nephritis and Renal Dysfunction grade 3-4 | 0 Participants |
| Cohort C | Number of Participants With High Grade (Grade 3-4 and Grade 5) Immune-Mediated Adverse Events (imAEs) | Hypothyroidism grade 3-4 | 0 Participants |
Secondary
Change From Baseline in Health-Related Quality of Life (HRQoL) Using Functional Assessment of Cancer Therapy-Lung (FACT-L)
FACT-L is a quality-of-life questionnaire which includes Lung Cancer Subscale (LCS) that assesses the treatment impact on lung cancer related symptoms in 5 domains: Physical, social/family, emotional, and functional well-being using a 5-point scale (0=not at all; 1=a little bit, 2=somewhat; 3=quite a bit; 4=very much) added to obtain total score. The ranges of possible total scores are 0-136 for the FACT-L with a higher score representing better quality of life, improved symptomatology and enhanced physical/functional outcomes. According to Functional Assessment of Chronic Illness Therapy scoring guidelines, in the event of missing responses for some of the questions, scores will be prorated using the average of the other answers in that scale. Baseline is defined as events that occur before the date/time of first dose. Post treatment visits include follow-up (FU) visit 1, FU visit 2, and subsequent survival FU visits to occur every 3 months up until survival FU visit 18.
Time frame: From baseline and up to subsequent survival follow-up visit 18 (Up to approximately 67 months)
Population: All treated participants who have an assessment at baseline and at least 1 follow-up assessment as pre-specified in Cohort A, B, and C
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort A | Change From Baseline in Health-Related Quality of Life (HRQoL) Using Functional Assessment of Cancer Therapy-Lung (FACT-L) | Survival Follow-up visit 18 | -43.33 Units on a Scale | — |
| Cohort A | Change From Baseline in Health-Related Quality of Life (HRQoL) Using Functional Assessment of Cancer Therapy-Lung (FACT-L) | Treatment Week 6 | -0.84 Units on a Scale | Standard Deviation 13.82 |
| Cohort A | Change From Baseline in Health-Related Quality of Life (HRQoL) Using Functional Assessment of Cancer Therapy-Lung (FACT-L) | Survival Follow-up visit 6 | 14.68 Units on a Scale | Standard Deviation 13.58 |
| Cohort A | Change From Baseline in Health-Related Quality of Life (HRQoL) Using Functional Assessment of Cancer Therapy-Lung (FACT-L) | Survival Follow-up visit 16 | 5.28 Units on a Scale | Standard Deviation 28.19 |
| Cohort A | Change From Baseline in Health-Related Quality of Life (HRQoL) Using Functional Assessment of Cancer Therapy-Lung (FACT-L) | Baseline | 94.89 Units on a Scale | Standard Deviation 19.33 |
| Cohort B | Change From Baseline in Health-Related Quality of Life (HRQoL) Using Functional Assessment of Cancer Therapy-Lung (FACT-L) | Baseline | 91.20 Units on a Scale | Standard Deviation 18.45 |
| Cohort B | Change From Baseline in Health-Related Quality of Life (HRQoL) Using Functional Assessment of Cancer Therapy-Lung (FACT-L) | Survival Follow-up visit 16 | -18.00 Units on a Scale | — |
| Cohort B | Change From Baseline in Health-Related Quality of Life (HRQoL) Using Functional Assessment of Cancer Therapy-Lung (FACT-L) | Survival Follow-up visit 6 | 3.81 Units on a Scale | Standard Deviation 18.59 |
| Cohort B | Change From Baseline in Health-Related Quality of Life (HRQoL) Using Functional Assessment of Cancer Therapy-Lung (FACT-L) | Treatment Week 6 | -0.30 Units on a Scale | Standard Deviation 14.87 |
| Cohort C | Change From Baseline in Health-Related Quality of Life (HRQoL) Using Functional Assessment of Cancer Therapy-Lung (FACT-L) | Baseline | 93.96 Units on a Scale | Standard Deviation 17.28 |
| Cohort C | Change From Baseline in Health-Related Quality of Life (HRQoL) Using Functional Assessment of Cancer Therapy-Lung (FACT-L) | Survival Follow-up visit 6 | 12.42 Units on a Scale | Standard Deviation 24.87 |
| Cohort C | Change From Baseline in Health-Related Quality of Life (HRQoL) Using Functional Assessment of Cancer Therapy-Lung (FACT-L) | Treatment Week 6 | 2.72 Units on a Scale | Standard Deviation 12.95 |
Secondary
Duration of Response (DoR)
DoR is defined as the time between the date of first confirmed complete response (CR) or partial response (PR) to the date of the first documented tumor progression per RECIST 1.1, or death due to any cause, whichever occurs first. CR= Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. PR= ≥ 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive Disease (PD)= ≥ 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study. The sum must also demonstrate an absolute increase of ≥ 5 mm. The appearance of one or more new lesions is also considered progression.
Time frame: From first dosing date to the date of first documented tumor progression or, death due to any cause, whichever occurs first (Up to approximately 67 months)
Population: All treated participants with confirmed CR or PR as pre-specified in Cohort A, B, and C
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort A | Duration of Response (DoR) | 27.56 Months |
| Cohort B | Duration of Response (DoR) | 13.01 Months |
| Cohort C | Duration of Response (DoR) | 26.05 Months |
Secondary
Objective Response Rate (ORR)
ORR is defined as the percentage of participants with a best overall response of confirmed complete response (CR) or partial response (PR). CR= Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. PR= ≥ 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Time frame: From first dosing date up to approximately 67 months
Population: All treated participants as pre-specified in Cohort A, B, and C
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort A | Objective Response Rate (ORR) | 37.3 Percentage of participants |
| Cohort B | Objective Response Rate (ORR) | 22.8 Percentage of participants |
| Cohort C | Objective Response Rate (ORR) | 45.6 Percentage of participants |
Secondary
Overall Survival (OS)
OS is defined as the time from first dosing date to the date of death. A participant who has not died will be censored at last known date alive.
Time frame: From first dosing date to the date of death (Up to approximately 67 months)
Population: All treated participants as pre-specified in Cohort A, B, and C
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort A | Overall Survival (OS) | 16.76 Months |
| Cohort B | Overall Survival (OS) | 10.45 Months |
| Cohort C | Overall Survival (OS) | 26.09 Months |
Secondary
Progression Free Survival (PFS)
PFS is defined as the time from first dosing date to the date of the first documented tumor progression, as determined by investigators (per RECIST v1.1), or death due to any cause, whichever occurs first. Progressive Disease (PD)= ≥ 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study. The sum must also demonstrate an absolute increase of ≥ 5 mm. The appearance of one or more new lesions is also considered progression.
Time frame: From first dosing date to the date of first documented tumor progression or, death due to any cause, whichever occurs first (Up to approximately 67 months)
Population: All treated participants as pre-specified in Cohort A, B, and C
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort A | Progression Free Survival (PFS) | 5.75 Months |
| Cohort B | Progression Free Survival (PFS) | 3.91 Months |
| Cohort C | Progression Free Survival (PFS) | 11.10 Months |