Advanced/Metastatic Head and Neck, Oesophageal and Cervical Cancers
Conditions
Brief summary
This is an open-label, multicenter, basket trial Phase II study to evaluate the antitumor activity of simlukafusp alfa in combination with atezolizumab in participants with advanced and/or metastatic solid tumors. Currently the focus is on participants with Head and Neck, oesophageal and cervical cancers with confirmed squamous cell carcinoma histology type.
Interventions
DRUGsimlukafusp alfa
simlukafusp alfa will be administered as per the dosage regimen mentioned in arm descriptions.
Atezolizumab will be administered as per the dosage regimen mentioned in arm descriptions.
DRUGGemcitabine
Single-agent treatment administered as per approved protocol.
DRUGVinorelbine
Single-agent treatment administered as per approved protocol.
Sponsors
Hoffmann-La Roche
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
* Participants who have progressed on at least one previous regimen of anticancer therapy (chemotherapy, mutation targeted therapy, and/or CPI therapy) * Measurable disease, as defined by RECIST Version 1.1 * Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1 or Karnofsky Performance Score greater than or equal to (\>=) 70 * Life expectancy of \>=12 weeks * Confirmed at least one tumor lesion with location accessible to safely biopsy per clinical judgment of the treating physician. Biopsies are not applicable to participants in Cohorts G, H, K, and L presenting with a single target lesion and absence of any non-target lesion. * Consent to provide an archival tumor tissue sample (if available, applicable to all participants) * Willingness to undergo baseline and on-treatment tumor biopsies for pharmacodynamics (PD) biomarker analysis (biopsies are optional for Cohort A) * Adequate cardiovascular function as defined in the study protocol * AEs related to any previous radiotherapy, chemotherapy, or surgical procedure must have resolved to Grade less than or equal to (\<=) 1, except alopecia (any grade) and Grade 2 peripheral neuropathy * Adequate haematological, liver, and renal functions. * Participants with unilateral pleural effusion (indications other than NSCLC) are eligible if they fulfill both of the following: 1. NYHA Class 1 2. Forced expiratory volume 1 (FEV1) and forced vital capacity (FVC) \>70% of predicted value; participants with lung metastases should present with DLCO \>60% of predicted value. * Participants with Gilbert's syndrome will be eligible for the study * Participants must have had confirmed diagnosis of recurrent or metastatic squamous cell carcinoma head and neck, or esophageal cancer or metastatic, persistent or recurrent squamous cervical cancer.
Exclusion criteria
* Symptomatic or untreated central nervous system (CNS) metastases * History of treated asymptomatic CNS metastases as described in the protocol * Spinal cord compression not definitively treated with surgery and/or radiation or previously diagnosed and treated spinal cord compression without evidence that disease has been clinically stable for \>=2 weeks before enrollment * Leptomeningeal disease * An active second malignancy * Penetrating tumor infiltration * Evidence of significant, uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of results * Episode of significant cardiovascular/cerebrovascular acute disease within 6 months before study treatment administration * History of significant vascular disease (for example, aortic aneurysm, aortic dissection) * Active or uncontrolled infections * Human immunodeficiency virus (HIV) or Active Hepatitis A, B, C, D or E infection (HAV/HBV/HCV/HDV/HEV). * Severe infection within 4 weeks before study treatment administration including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia. * History of chronic liver disease or evidence of hepatic cirrhosis * Dementia or altered mental status that would prohibit informed consent * History of, active or suspicion of autoimmune disease * History of idiopathic pulmonary fibrosis, pneumonitis (including drug-induced), organizing pneumonia (bronchiolitis obliterans, cryptogenic organizing pneumonia, etc.), or evidence of active pneumonitis on screening chest computed tomography (CT) scan. History of radiation pneumonitis in the radiation field (fibrosis) is permitted * Bilateral pleural effusion confirmed by X-ray * Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding that give reasonable suspicion of a disease or condition that would contraindicate the use of an investigational drug * Concurrent therapy with any other investigational drug * Immunomodulating agents as described in study protocol * Chronic use of steroids * Last dose with any cytostatic treatments \< 28 days before study treatment administration * Radiotherapy within the last 4 weeks before start of study treatment administration, with the exception of limited field palliative radiotherapy * Administration of a live, attenuated vaccine within 4 weeks before Cycle 1 Day 1 or at any time during the study and 5 months after the last dose of atezolizumab * Major surgery or significant traumatic injury \<28 days before study treatment administration (excluding fine needle biopsies) or if wound healing has not completed after surgery or anticipation of the need for major surgery during study treatment * Known hypersensitivity to any of the components of the simlukafusp alfa drug product or atezolizumab drug product * Severe dyspnea at rest or requiring supplementary oxygen therapy Locally curative options are available for participant's disease.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Objective Response Rate (ORR) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 | Baseline up to disease progression or study treatment discontinuation (up to 38 months) | ORR was defined as the percentage of participants with observed tumor response of complete response (CR), or partial response (PR) determined according to RECIST version 1.1. CR was defined as the disappearance of all target lesions with reduction in target/non-target pathological lymph nodes to \<10 millimeters (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. The percentages of participants are rounded off to the nearest single decimal point. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Response (DoR) According to RECIST Version 1.1 | From first occurrence of documented CR or PR up to disease progression or study treatment discontinuation (assessed every 8 weeks after study treatment start for the first year, and every 12 weeks thereafter, up to 38 months) | DoR was determined for participants who had a best overall response of CR or PR. CR was defined as the disappearance of all target lesions with a reduction in target/non-target pathological lymph nodes 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. DoR was defined as the time from first occurrence of a documented objective response until the time of documented disease progression or death from any cause during treatment, whichever occurs first. Participants that did not have documented progressive disease or death during the study were censored at the day of the last tumor assessment. |
| Progression-Free Survival (PFS) According to RECIST Version 1.1 | Study treatment initiation up to disease progression or study treatment discontinuation (up to 38 months) | PFS was defined as the time from study treatment initiation (Cycle 1 Day 1 \[1 cycle=14 days for QW/Q2W cohorts; 1 cycle=21 days for Q3W cohorts\]) to the first occurrence of documented disease progression (based on Investigator's assessment) or death from any cause during treatment, whichever occurs first. Participants that did not have documented progressive disease or death during the study were censored at the day of the last tumor assessment. |
| Overall Survival (OS) | From first dose of study treatment up to death due to any cause (up to approximately 47 months) | OS was defined as the time from the first dose of study treatment to the time of death from any cause on study. Participants who were still alive at the time of analysis were censored at the last date known alive. |
| Percentage of Participants With Adverse Events (AEs) | Baseline up to end of the study (up to approximately 47 months) | An AE is any untoward medical occurrence in a participant or clinical investigation subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. |
| Percentage of Participants With Disease Control Rate (DCR) Determined According to RECIST Version 1.1 | Baseline up to disease progression or study treatment discontinuation (up to 38 months) | DCR was defined as the percentage of participants with observed tumor response of CR, PR or stable disease (SD) determined according to RECIST version 1.1. CR was defined as the disappearance of all target lesions with reduction in target/non-target pathological lymph nodes 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 to qualify for PR nor sufficient increase to qualify for progressive disease (PD). PD is at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study including baseline (nadir). The percentages of participants are rounded off to the nearest single decimal point. |
| Change From Baseline in Density of Cluster of Differentiation (CD) 8 Positive (CD8+) Cells According to Immunohistochemical Methods | Baseline up 2 months | — |
| Change From Baseline in Density of Cluster of Differentiation 3 Negative (CD3-) Perforin Positive Cells According to Immunohistochemical Methods | Baseline up to 2 months | — |
| Change From Baseline in Density of PD-L1 According to Immunohistochemical Methods | Baseline up to 2 months | — |
| Percentage of Participants by Programmed Death-Ligand 1 (PD-L1) Status According to Immunohistochemical Methods | Baseline | — |
Countries
Belgium, France, Germany, Israel, New Zealand, Poland, Russia, Singapore, South Korea, Spain, Switzerland, Taiwan, Turkey (Türkiye), United Kingdom, United States
Participant flow
Recruitment details
Participants took part in the study at 42 investigative sites in Belgium, France, Germany, Israel, Korea, New Zealand, Poland, Russia, Singapore, Spain, Switzerland, Taiwan, Turkey, United Kingdom, USA from 19 February 2018 to 30 December 2021
Pre-assignment details
A total of 256 participants were enrolled. 95 participants in non-small cell lung cancer (NCSLC) cohorts \[Part I: A, B, D, F & Part II: E\] & 161 participants in squamous cell carcinoma (SCC) cohort (78 with head and neck SCC (HNSCC) \[Part III: G, H, K\], 35 in esophageal SCC (ESCC) \[Part 3: I and M\], & 48 in cervical SCC (CSCC) \[Part 3 J & N\] received simlukafusp alfa & atezolizumab. No participants were enrolled in Cohorts C & L as emerging data did not lead to the need to open these cohorts.
Participants by arm
| Arm | Count |
|---|---|
| NSCLC: Part I Cohort A (QW/Q2W) CPI-naïve participants with NSCLC, received simlukafusp alfa, 10 mg, IV infusion, QW for the first 4 weeks, and Q2W until disease progression, unacceptable toxicity, or withdrawal of consent, or for a maximum of 38 months. Participants also received atezolizumab, 840 mg, IV infusion, Q2W in combination with simlukafusp alfa until disease progression, unacceptable toxicity, or withdrawal of consent, or for a maximum of 38 months. | 26 |
| NSCLC: Part I Cohort B (QW/Q2W) CPI-experienced participants with NSCLC, received simlukafusp alfa, 10 mg, IV infusion, QW for the first 4 weeks, and Q2W until disease progression, unacceptable toxicity, or withdrawal of consent, or for a maximum of 15.6 months. Participants also received atezolizumab, 840 mg, IV infusion, Q2W in combination with simlukafusp alfa until disease progression, unacceptable toxicity, or withdrawal of consent, or for a maximum of 15.6 months. | 32 |
| NSCLC: Part I Cohort D, Arm 1 (QW/Q2W) CPI-experienced participants with NSCLC previously treated with platinum-containing regimen and docetaxel, received simlukafusp alfa, 10 mg, IV infusion, QW for the first 4 weeks, and Q2W until disease progression, unacceptable toxicity, or withdrawal of consent, or for a maximum of 2.7 months. Participants also received atezolizumab, 840 mg, IV infusion, Q2W in combination with simlukafusp alfa until disease progression, unacceptable toxicity, or withdrawal of consent, or for a maximum of 2.7 months. | 3 |
| NSCLC: Part I Cohort D, Arm 2 (Q3W) CPI-experienced participants with NSCLC previously treated with platinum-containing regimen and docetaxel received simlukafusp alfa, 10 mg, IV infusion Q3W in combination with atezolizumab, 1200 mg, IV infusion, Q3W until disease progression, unacceptable toxicity, or withdrawal of consent, or for a maximum of 5.4 months. | 5 |
| NSCLC: Part I Cohort D, Arm 3 (Q3W) CPI-experienced participants with NSCLC who were previously treated with platinum-containing regimen and docetaxel received a gemcitabine, IV infusion as per approved protocol. Participants who had documented radiographic disease progression during or after treatment with gemcitabine received simlukafusp alfa, 10 mg, IV infusion Q3W in combination with atezolizumab, 1200 mg, IV infusion, Q3W until disease progression, unacceptable toxicity, or withdrawal of consent, or for a maximum of 1.3 months. | 2 |
| NSCLC: Part I Cohort F (Q3W) CPI-experienced, docetaxel naive participants with NSCLC who experienced disease progression during or after treatment with a platinum-containing regimen received, simlukafusp alfa, 10 mg, IV infusion, Q3W in combination with atezolizumab, 1200 mg, IV infusion, Q3W until disease progression, unacceptable toxicity, or withdrawal of consent, or for a maximum of 26 months. | 22 |
| NSCLC: Part II Cohort E, Arm 1 (QW/Q2W) NSCLC participants without prior treatment for metastatic disease and with high PD-L1 expression levels, received simlukafusp alfa, 10 mg, IV infusion, QW for the first 4 weeks, and Q2W until disease progression, unacceptable toxicity, or withdrawal of consent, or for a maximum of 31.3 months. Participants also received atezolizumab, 840 mg, IV infusion, Q2W in combination with simlukafusp alfa until disease progression, unacceptable toxicity, or withdrawal of consent, or for a maximum of 31.3 months. | 3 |
| NSCLC: Part II Cohort E, Arm 2 (Q3W) NSCLC participants without prior treatment for metastatic disease and with high PD-L1 expression levels, received simlukafusp alfa, 10 mg, IV infusion Q3W in combination with atezolizumab, 1200 mg, IV infusion, Q3W until disease progression, unacceptable toxicity, or withdrawal of consent, or for a maximum of 18.6 months. | 2 |
| SCCHN: Part III Cohort G (Q3W) CPI-naïve participants with SCCHN, received simlukafusp alfa, 10 mg, IV infusion, Q3W in combination with atezolizumab, 1200 mg, IV infusion, Q3W until disease progression, unacceptable toxicity, or withdrawal of consent, or for a maximum of 24.6 months. | 23 |
| SCCHN: Part III Cohort H (Q3W) CPI-experienced participants with SCCHN, received simlukafusp alfa, 10 mg, IV infusion, Q3W in combination with atezolizumab, 1200 mg, IV infusion, Q3W until disease progression, unacceptable toxicity, or withdrawal of consent, or for a maximum of 10.3 months. | 30 |
| ESCC: Part III Cohort I (Q3W) CPI-naïve participants with ESCC who were previously treated with standard therapy received simlukafusp alfa, 10 mg, IV infusion, Q3W in combination with atezolizumab, 1200 mg, IV infusion, Q3W until disease progression, unacceptable toxicity, or withdrawal of consent, or for a maximum of 30.5 months. | 33 |
| CSCC: Part III Cohort J (Q3W) CPI-naïve participants with CSCC who were previously treated with standard therapy, received simlukafusp alfa, 10 mg, IV infusion, Q3W in combination with atezolizumab, 1200 mg, IV infusion, Q3W until disease progression, unacceptable toxicity, or withdrawal of consent, or for a maximum of 28.8 months. | 47 |
| SCCHN: Part III Cohort K (QW/Q2W) CPI-naïve participants with SCCHN, received simlukafusp alfa, 10 mg, IV infusion, QW for the first 4 weeks, and Q2W until disease progression, unacceptable toxicity, or withdrawal of consent, or for a maximum of 24.3 months. Participants also received atezolizumab, 840 mg, IV infusion, Q2W in combination with simlukafusp alfa until disease progression, unacceptable toxicity, or withdrawal of consent, or for a maximum of 24.3 months. | 25 |
| ESCC: Part III Cohort M (QW/Q2W) Participants with ESCC, received simlukafusp alfa, 10 mg, IV infusion, QW for the first 4 weeks, and Q2W until disease progression, unacceptable toxicity, or withdrawal of consent, or for a maximum of 4.1 months. Participants also received atezolizumab, 840 mg, IV infusion, Q2W in combination with simlukafusp alfa until disease progression, unacceptable toxicity, or withdrawal of consent, or for a maximum of 4.1 months. | 2 |
| CSCC: Part III Cohort N (QW/Q2W) Participants with CSCC, received simlukafusp alfa, 10 mg, IV infusion, QW for the first 4 weeks, and Q2W until disease progression, unacceptable toxicity, or withdrawal of consent, or for a maximum of 0.68 months. Participants also received atezolizumab, 840 mg, IV infusion, Q2W in combination with simlukafusp alfa until disease progression, unacceptable toxicity, or withdrawal of consent, or for a maximum of 0.68 months. | 1 |
| Total | 256 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 | FG011 | FG012 | FG013 | FG014 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Death | 12 | 21 | 2 | 5 | 1 | 12 | 1 | 1 | 12 | 20 | 21 | 21 | 14 | 2 | 1 |
| Overall Study | Lost to Follow-up | 1 | 3 | 0 | 0 | 0 | 2 | 1 | 0 | 1 | 2 | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Progressive Disease | 0 | 0 | 1 | 0 | 0 | 1 | 0 | 0 | 2 | 1 | 1 | 0 | 1 | 0 | 0 |
| Overall Study | Reason not specified | 3 | 0 | 0 | 0 | 0 | 3 | 1 | 0 | 0 | 1 | 2 | 6 | 1 | 0 | 0 |
| Overall Study | Site Terminated by Sponsor | 5 | 5 | 0 | 0 | 1 | 3 | 0 | 1 | 4 | 5 | 3 | 11 | 6 | 0 | 0 |
| Overall Study | Symptomatic Deterioration | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 1 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 1 | 3 | 2 | 3 | 0 | 0 |
Baseline characteristics
| Characteristic | NSCLC: Part I Cohort B (QW/Q2W) | Total | CSCC: Part III Cohort N (QW/Q2W) | ESCC: Part III Cohort M (QW/Q2W) | SCCHN: Part III Cohort K (QW/Q2W) | CSCC: Part III Cohort J (Q3W) | ESCC: Part III Cohort I (Q3W) | SCCHN: Part III Cohort H (Q3W) | NSCLC: Part I Cohort A (QW/Q2W) | SCCHN: Part III Cohort G (Q3W) | NSCLC: Part II Cohort E, Arm 2 (Q3W) | NSCLC: Part II Cohort E, Arm 1 (QW/Q2W) | NSCLC: Part I Cohort F (Q3W) | NSCLC: Part I Cohort D, Arm 3 (Q3W) | NSCLC: Part I Cohort D, Arm 2 (Q3W) | NSCLC: Part I Cohort D, Arm 1 (QW/Q2W) |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 59.8 years STANDARD_DEVIATION 9.9 | 57.6 years STANDARD_DEVIATION 10.8 | 49.0 years | 67.0 years STANDARD_DEVIATION 15.6 | 55.8 years STANDARD_DEVIATION 11.7 | 51.3 years STANDARD_DEVIATION 11.2 | 63.1 years STANDARD_DEVIATION 9.6 | 58.8 years STANDARD_DEVIATION 8.2 | 58.0 years STANDARD_DEVIATION 10.5 | 55.7 years STANDARD_DEVIATION 12.8 | 68.0 years STANDARD_DEVIATION 2.8 | 56.7 years STANDARD_DEVIATION 0.6 | 57.4 years STANDARD_DEVIATION 8.9 | 63.5 years STANDARD_DEVIATION 4.9 | 65.6 years STANDARD_DEVIATION 4.3 | 63.7 years STANDARD_DEVIATION 3.8 |
| Race/Ethnicity, Customized Hispanic or Latino | 1 Participants | 3 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 28 Participants | 213 Participants | 1 Participants | 1 Participants | 23 Participants | 33 Participants | 27 Participants | 21 Participants | 23 Participants | 22 Participants | 2 Participants | 3 Participants | 20 Participants | 2 Participants | 4 Participants | 3 Participants |
| Race/Ethnicity, Customized Not Stated | 2 Participants | 29 Participants | 0 Participants | 1 Participants | 2 Participants | 9 Participants | 4 Participants | 7 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Unknown | 1 Participants | 11 Participants | 0 Participants | 0 Participants | 0 Participants | 5 Participants | 2 Participants | 1 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 5 Participants | 40 Participants | 0 Participants | 1 Participants | 5 Participants | 0 Participants | 6 Participants | 5 Participants | 9 Participants | 3 Participants | 0 Participants | 1 Participants | 5 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 4 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 2 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 29 Participants | 0 Participants | 1 Participants | 2 Participants | 13 Participants | 5 Participants | 8 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 26 Participants | 181 Participants | 1 Participants | 0 Participants | 18 Participants | 33 Participants | 22 Participants | 16 Participants | 15 Participants | 19 Participants | 2 Participants | 2 Participants | 17 Participants | 2 Participants | 5 Participants | 3 Participants |
| Sex: Female, Male Female | 10 Participants | 110 Participants | 1 Participants | 0 Participants | 6 Participants | 47 Participants | 10 Participants | 7 Participants | 10 Participants | 5 Participants | 0 Participants | 1 Participants | 11 Participants | 1 Participants | 0 Participants | 1 Participants |
| Sex: Female, Male Male | 22 Participants | 146 Participants | 0 Participants | 2 Participants | 19 Participants | 0 Participants | 23 Participants | 23 Participants | 16 Participants | 18 Participants | 2 Participants | 2 Participants | 11 Participants | 1 Participants | 5 Participants | 2 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 | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk | EG012 affected / at risk | EG013 affected / at risk | EG014 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 12 / 26 | 21 / 32 | 3 / 3 | 5 / 5 | 1 / 2 | 12 / 22 | 1 / 3 | 1 / 2 | 14 / 23 | 20 / 30 | 21 / 33 | 21 / 47 | 14 / 25 | 2 / 2 | 1 / 1 |
| other Total, other adverse events | 25 / 26 | 32 / 32 | 3 / 3 | 5 / 5 | 2 / 2 | 21 / 22 | 3 / 3 | 2 / 2 | 23 / 23 | 29 / 30 | 33 / 33 | 47 / 47 | 24 / 25 | 2 / 2 | 1 / 1 |
| serious Total, serious adverse events | 13 / 26 | 25 / 32 | 0 / 3 | 3 / 5 | 2 / 2 | 14 / 22 | 1 / 3 | 1 / 2 | 15 / 23 | 22 / 30 | 20 / 33 | 32 / 47 | 14 / 25 | 1 / 2 | 1 / 1 |
Outcome results
Primary
Percentage of Participants With Objective Response Rate (ORR) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
ORR was defined as the percentage of participants with observed tumor response of complete response (CR), or partial response (PR) determined according to RECIST version 1.1. CR was defined as the disappearance of all target lesions with reduction in target/non-target pathological lymph nodes to \<10 millimeters (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. The percentages of participants are rounded off to the nearest single decimal point.
Time frame: Baseline up to disease progression or study treatment discontinuation (up to 38 months)
Population: Response evaluable population included all participants in the safety population who received at least one dose of simlukafusp alfa/atezolizumab and who had at least one baseline and one on-study tumor assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| NSCLC: Part I Cohort A (QW/Q2W) | Percentage of Participants With Objective Response Rate (ORR) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 | 19.2 percentage of participants |
| NSCLC: Part I Cohort B (QW/Q2W) | Percentage of Participants With Objective Response Rate (ORR) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 | 6.3 percentage of participants |
| NSCLC: Part I Cohort D, Arm 1 (QW/Q2W) | Percentage of Participants With Objective Response Rate (ORR) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 | 0 percentage of participants |
| NSCLC: Part I Cohort D, Arm 2 (Q3W) | Percentage of Participants With Objective Response Rate (ORR) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 | 0 percentage of participants |
| NSCLC: Part I Cohort F (Q3W) | Percentage of Participants With Objective Response Rate (ORR) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 | 4.8 percentage of participants |
| NSCLC: Part II Cohort E, Arm 1 (QW/Q2W) | Percentage of Participants With Objective Response Rate (ORR) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 | 66.7 percentage of participants |
| NSCLC: Part II Cohort E, Arm 2 (Q3W) | Percentage of Participants With Objective Response Rate (ORR) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 | 50.0 percentage of participants |
| SCCHN: Part III Cohort G (Q3W) | Percentage of Participants With Objective Response Rate (ORR) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 | 18.2 percentage of participants |
| SCCHN: Part III Cohort H (Q3W) | Percentage of Participants With Objective Response Rate (ORR) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 | 3.6 percentage of participants |
| ESCC: Part III Cohort I (Q3W) | Percentage of Participants With Objective Response Rate (ORR) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 | 21.9 percentage of participants |
| CSCC: Part III Cohort J (Q3W) | Percentage of Participants With Objective Response Rate (ORR) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 | 27.3 percentage of participants |
| SCCHN: Part III Cohort K (QW/Q2W) | Percentage of Participants With Objective Response Rate (ORR) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 | 4.0 percentage of participants |
| ESCC: Part III Cohort M (QW/Q2W) | Percentage of Participants With Objective Response Rate (ORR) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 | 0 percentage of participants |
| CSCC: Part III Cohort N (QW/Q2W) | Percentage of Participants With Objective Response Rate (ORR) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 | 0 percentage of participants |
Secondary
Change From Baseline in Density of Cluster of Differentiation 3 Negative (CD3-) Perforin Positive Cells According to Immunohistochemical Methods
Time frame: Baseline up to 2 months
Population: Data was not collected for this outcome measure post-baseline as baseline data was not matured and sufficient to be analyzed during analysis.
Secondary
Change From Baseline in Density of Cluster of Differentiation (CD) 8 Positive (CD8+) Cells According to Immunohistochemical Methods
Time frame: Baseline up 2 months
Population: Data was not collected for this outcome measure post-baseline as baseline data was not matured and sufficient to be analyzed during analysis.
Secondary
Change From Baseline in Density of PD-L1 According to Immunohistochemical Methods
Time frame: Baseline up to 2 months
Population: Data was not collected for this outcome measure post-baseline as baseline data was not matured and sufficient to analyze PD-L1 impact.
Secondary
Duration of Response (DoR) According to RECIST Version 1.1
DoR was determined for participants who had a best overall response of CR or PR. CR was defined as the disappearance of all target lesions with a reduction in target/non-target pathological lymph nodes 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. DoR was defined as the time from first occurrence of a documented objective response until the time of documented disease progression or death from any cause during treatment, whichever occurs first. Participants that did not have documented progressive disease or death during the study were censored at the day of the last tumor assessment.
Time frame: From first occurrence of documented CR or PR up to disease progression or study treatment discontinuation (assessed every 8 weeks after study treatment start for the first year, and every 12 weeks thereafter, up to 38 months)
Population: Data was not collected for this outcome measure due to premature termination of the study by the sponsor.
Secondary
Overall Survival (OS)
OS was defined as the time from the first dose of study treatment to the time of death from any cause on study. Participants who were still alive at the time of analysis were censored at the last date known alive.
Time frame: From first dose of study treatment up to death due to any cause (up to approximately 47 months)
Population: Response evaluable population included all participants in the safety population who received at least one dose of simlukafusp alfa/atezolizumab and who had at least one baseline and one on-study tumor assessment. Due to early termination of the study, matured median for OS could not be achieved, hence as planned and pre-specified in the protocol, the data for OS was not analyzed and not reported.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| NSCLC: Part I Cohort A (QW/Q2W) | Overall Survival (OS) | NA months |
| NSCLC: Part I Cohort B (QW/Q2W) | Overall Survival (OS) | NA months |
| NSCLC: Part I Cohort D, Arm 1 (QW/Q2W) | Overall Survival (OS) | NA months |
| NSCLC: Part I Cohort D, Arm 2 (Q3W) | Overall Survival (OS) | NA months |
| NSCLC: Part I Cohort F (Q3W) | Overall Survival (OS) | NA months |
| NSCLC: Part II Cohort E, Arm 1 (QW/Q2W) | Overall Survival (OS) | NA months |
| NSCLC: Part II Cohort E, Arm 2 (Q3W) | Overall Survival (OS) | NA months |
| SCCHN: Part III Cohort G (Q3W) | Overall Survival (OS) | NA months |
| SCCHN: Part III Cohort H (Q3W) | Overall Survival (OS) | NA months |
| ESCC: Part III Cohort I (Q3W) | Overall Survival (OS) | NA months |
| CSCC: Part III Cohort J (Q3W) | Overall Survival (OS) | NA months |
| SCCHN: Part III Cohort K (QW/Q2W) | Overall Survival (OS) | NA months |
| ESCC: Part III Cohort M (QW/Q2W) | Overall Survival (OS) | NA months |
| CSCC: Part III Cohort N (QW/Q2W) | Overall Survival (OS) | NA months |
Secondary
Percentage of Participants by Programmed Death-Ligand 1 (PD-L1) Status According to Immunohistochemical Methods
Time frame: Baseline
Population: Data was not collected for this outcome measure post-baseline as baseline data was not matured and sufficient to analyze PD-L1 impact.
Secondary
Percentage of Participants With Adverse Events (AEs)
An AE is any untoward medical occurrence in a participant or clinical investigation subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
Time frame: Baseline up to end of the study (up to approximately 47 months)
Population: Safety Population included all participants who received at least one dose of study treatment, whether prematurely withdrawn from the study or not.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| NSCLC: Part I Cohort A (QW/Q2W) | Percentage of Participants With Adverse Events (AEs) | 100 percentage of participants |
| NSCLC: Part I Cohort B (QW/Q2W) | Percentage of Participants With Adverse Events (AEs) | 100 percentage of participants |
| NSCLC: Part I Cohort D, Arm 1 (QW/Q2W) | Percentage of Participants With Adverse Events (AEs) | 100 percentage of participants |
| NSCLC: Part I Cohort D, Arm 2 (Q3W) | Percentage of Participants With Adverse Events (AEs) | 100 percentage of participants |
| NSCLC: Part I Cohort D, Arm 3 (Q3W) | Percentage of Participants With Adverse Events (AEs) | 100 percentage of participants |
| NSCLC: Part I Cohort F (Q3W) | Percentage of Participants With Adverse Events (AEs) | 100 percentage of participants |
| NSCLC: Part II Cohort E, Arm 1 (QW/Q2W) | Percentage of Participants With Adverse Events (AEs) | 100 percentage of participants |
| NSCLC: Part II Cohort E, Arm 2 (Q3W) | Percentage of Participants With Adverse Events (AEs) | 100 percentage of participants |
| SCCHN: Part III Cohort G (Q3W) | Percentage of Participants With Adverse Events (AEs) | 100 percentage of participants |
| SCCHN: Part III Cohort H (Q3W) | Percentage of Participants With Adverse Events (AEs) | 100 percentage of participants |
| ESCC: Part III Cohort I (Q3W) | Percentage of Participants With Adverse Events (AEs) | 100 percentage of participants |
| CSCC: Part III Cohort J (Q3W) | Percentage of Participants With Adverse Events (AEs) | 100 percentage of participants |
| SCCHN: Part III Cohort K (QW/Q2W) | Percentage of Participants With Adverse Events (AEs) | 100 percentage of participants |
| ESCC: Part III Cohort M (QW/Q2W) | Percentage of Participants With Adverse Events (AEs) | 100 percentage of participants |
| CSCC: Part III Cohort N (QW/Q2W) | Percentage of Participants With Adverse Events (AEs) | 100 percentage of participants |
Secondary
Percentage of Participants With Disease Control Rate (DCR) Determined According to RECIST Version 1.1
DCR was defined as the percentage of participants with observed tumor response of CR, PR or stable disease (SD) determined according to RECIST version 1.1. CR was defined as the disappearance of all target lesions with reduction in target/non-target pathological lymph nodes 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 to qualify for PR nor sufficient increase to qualify for progressive disease (PD). PD is at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study including baseline (nadir). The percentages of participants are rounded off to the nearest single decimal point.
Time frame: Baseline up to disease progression or study treatment discontinuation (up to 38 months)
Population: Response evaluable population included all participants in the safety population who received at least one dose of simlukafusp alfa/atezolizumab and who had at least one baseline and one on-study tumor assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| NSCLC: Part I Cohort A (QW/Q2W) | Percentage of Participants With Disease Control Rate (DCR) Determined According to RECIST Version 1.1 | 53.8 percentage of participants |
| NSCLC: Part I Cohort B (QW/Q2W) | Percentage of Participants With Disease Control Rate (DCR) Determined According to RECIST Version 1.1 | 62.5 percentage of participants |
| NSCLC: Part I Cohort D, Arm 1 (QW/Q2W) | Percentage of Participants With Disease Control Rate (DCR) Determined According to RECIST Version 1.1 | 0 percentage of participants |
| NSCLC: Part I Cohort D, Arm 2 (Q3W) | Percentage of Participants With Disease Control Rate (DCR) Determined According to RECIST Version 1.1 | 20.0 percentage of participants |
| NSCLC: Part I Cohort F (Q3W) | Percentage of Participants With Disease Control Rate (DCR) Determined According to RECIST Version 1.1 | 57.1 percentage of participants |
| NSCLC: Part II Cohort E, Arm 1 (QW/Q2W) | Percentage of Participants With Disease Control Rate (DCR) Determined According to RECIST Version 1.1 | 66.7 percentage of participants |
| NSCLC: Part II Cohort E, Arm 2 (Q3W) | Percentage of Participants With Disease Control Rate (DCR) Determined According to RECIST Version 1.1 | 50.0 percentage of participants |
| SCCHN: Part III Cohort G (Q3W) | Percentage of Participants With Disease Control Rate (DCR) Determined According to RECIST Version 1.1 | 50.0 percentage of participants |
| SCCHN: Part III Cohort H (Q3W) | Percentage of Participants With Disease Control Rate (DCR) Determined According to RECIST Version 1.1 | 14.3 percentage of participants |
| ESCC: Part III Cohort I (Q3W) | Percentage of Participants With Disease Control Rate (DCR) Determined According to RECIST Version 1.1 | 43.8 percentage of participants |
| CSCC: Part III Cohort J (Q3W) | Percentage of Participants With Disease Control Rate (DCR) Determined According to RECIST Version 1.1 | 68.2 percentage of participants |
| SCCHN: Part III Cohort K (QW/Q2W) | Percentage of Participants With Disease Control Rate (DCR) Determined According to RECIST Version 1.1 | 36.0 percentage of participants |
| ESCC: Part III Cohort M (QW/Q2W) | Percentage of Participants With Disease Control Rate (DCR) Determined According to RECIST Version 1.1 | 50.0 percentage of participants |
| CSCC: Part III Cohort N (QW/Q2W) | Percentage of Participants With Disease Control Rate (DCR) Determined According to RECIST Version 1.1 | 0 percentage of participants |
Secondary
Progression-Free Survival (PFS) According to RECIST Version 1.1
PFS was defined as the time from study treatment initiation (Cycle 1 Day 1 \[1 cycle=14 days for QW/Q2W cohorts; 1 cycle=21 days for Q3W cohorts\]) to the first occurrence of documented disease progression (based on Investigator's assessment) or death from any cause during treatment, whichever occurs first. Participants that did not have documented progressive disease or death during the study were censored at the day of the last tumor assessment.
Time frame: Study treatment initiation up to disease progression or study treatment discontinuation (up to 38 months)
Population: Response evaluable population included all participants in the safety population who received at least one dose of simlukafusp alfa/atezolizumab and who had at least one baseline and one on-study tumor assessment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| NSCLC: Part I Cohort A (QW/Q2W) | Progression-Free Survival (PFS) According to RECIST Version 1.1 | 3.5 months |
| NSCLC: Part I Cohort B (QW/Q2W) | Progression-Free Survival (PFS) According to RECIST Version 1.1 | 3.7 months |
| NSCLC: Part I Cohort D, Arm 1 (QW/Q2W) | Progression-Free Survival (PFS) According to RECIST Version 1.1 | 2.0 months |
| NSCLC: Part I Cohort D, Arm 2 (Q3W) | Progression-Free Survival (PFS) According to RECIST Version 1.1 | 2.0 months |
| NSCLC: Part I Cohort F (Q3W) | Progression-Free Survival (PFS) According to RECIST Version 1.1 | 3.5 months |
| NSCLC: Part II Cohort E, Arm 1 (QW/Q2W) | Progression-Free Survival (PFS) According to RECIST Version 1.1 | NA months |
| NSCLC: Part II Cohort E, Arm 2 (Q3W) | Progression-Free Survival (PFS) According to RECIST Version 1.1 | 10.5 months |
| SCCHN: Part III Cohort G (Q3W) | Progression-Free Survival (PFS) According to RECIST Version 1.1 | 2.5 months |
| SCCHN: Part III Cohort H (Q3W) | Progression-Free Survival (PFS) According to RECIST Version 1.1 | 1.9 months |
| ESCC: Part III Cohort I (Q3W) | Progression-Free Survival (PFS) According to RECIST Version 1.1 | 1.9 months |
| CSCC: Part III Cohort J (Q3W) | Progression-Free Survival (PFS) According to RECIST Version 1.1 | 3.7 months |
| SCCHN: Part III Cohort K (QW/Q2W) | Progression-Free Survival (PFS) According to RECIST Version 1.1 | 1.9 months |
| ESCC: Part III Cohort M (QW/Q2W) | Progression-Free Survival (PFS) According to RECIST Version 1.1 | 2.6 months |
| CSCC: Part III Cohort N (QW/Q2W) | Progression-Free Survival (PFS) According to RECIST Version 1.1 | 1.9 months |