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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT04585815




Registration number
NCT04585815
Ethics application status
Date submitted
30/09/2020
Date registered
14/10/2020
Date last updated
5/04/2024

Titles & IDs
Public title
Study of Immunotherapy (Sasanlimab) in Combination With Targeted Therapies in People With Advanced Non-small Cell Lung Cancer (NSCLC) (Landscape 1011 Study)
Scientific title
A Phase 1b/2 Open Label Umbrella Study of Sasanlimab Combined With Anti-Cancer Therapies Targeting Multiple Molecular Mechanisms in Participants With Non-Small Cell Lung Cancer (NSCLC)
Secondary ID [1] 0 0
2020-002829-28
Secondary ID [2] 0 0
B8011011
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Carcinoma, Non-Small-Cell Lung 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lung - Mesothelioma
Cancer 0 0 0 0
Lung - Non small cell
Cancer 0 0 0 0
Lung - Small cell

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Sasanlimab Prefilled syringe
Treatment: Drugs - Encorafenib
Treatment: Drugs - Binimetinib
Treatment: Drugs - Sasanlimab
Treatment: Drugs - Axitinib
Treatment: Drugs - SEA-TGT

Experimental: Sub-Study A - Sasanlimab will be administered subcutaneously. Encorafenib & binimetinib will be administered orally. Treatments will be administered until progressive disease, unacceptable AE, participant withdraws, or study is terminated.

Experimental: Sub-Study B - Sasanlimab will be administered subcutaneously. Axitinib will be administered orally. SEA-TGT will be administered intravenously. Treatments will be administered until progressive disease, unacceptable AE, patient withdraws, or study is terminated.


Treatment: Drugs: Sasanlimab Prefilled syringe
prefilled syringe

Treatment: Drugs: Encorafenib
capsules

Treatment: Drugs: Binimetinib
tablets

Treatment: Drugs: Sasanlimab
solution supplied in vials

Treatment: Drugs: Axitinib
tablets

Treatment: Drugs: SEA-TGT
solution in vials
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Phase 1b of Sub-Study A: Percentage of Participants With Dose-Limiting Toxicities (DLT)
Timepoint [1] 0 0
Day 1 up to Day 28 of Cycle 1
Primary outcome [2] 0 0
Phase 2 of Sub-Study A: Durable Objective Response Rate (ORR)
Timepoint [2] 0 0
From the date of first CR or PR until the date of the first documentation of PD, death, or start of new anticancer therapy
Secondary outcome [1] 0 0
Phase 1b of Sub-Study A: Number of Participants With Adverse Events (AEs) Graded According to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0
Timepoint [1] 0 0
From the start of study treatment (Cycle1 Day1) up to 30 days after last dose of study treatment (approximately 44 months)
Secondary outcome [2] 0 0
Phase 2 of Sub-Study A: Number of Participants With Adverse Events Graded According to NCI-CTCAE Version 5.0
Timepoint [2] 0 0
From the start of study treatment (Cycle1 Day1) up to 30 days after last dose of study treatment
Secondary outcome [3] 0 0
Phase 1b of Sub-Study A: Number of Participants With Laboratory Abnormalities
Timepoint [3] 0 0
From the start of study treatment (Cycle1 Day1) up to 30 days after last dose of study treatment (approximately 44 months)
Secondary outcome [4] 0 0
Phase 2 of Sub-Study A: Number of Participants With Laboratory Abnormalities
Timepoint [4] 0 0
From the start of study treatment (Cycle1 Day1) up to 30 days after last dose of study treatment
Secondary outcome [5] 0 0
Phase 1b of Sub-Study A: Durable Objective Response Rate
Timepoint [5] 0 0
From the date of first CR or PR until the date of the first documentation of PD, death, or start of new anticancer therapy (approximately 44 months)
Secondary outcome [6] 0 0
Phase 1b of Sub-Study A: Objective Response Rate
Timepoint [6] 0 0
From the date of first dose of study treatment until the date of the first documentation of PD (approximately 44 months)
Secondary outcome [7] 0 0
Phase 2 of Sub-Study A: Objective Response Rate
Timepoint [7] 0 0
From the date of first dose of study treatment until the date of the first documentation of PD
Secondary outcome [8] 0 0
Phase 2 of Sub-Study A: Duration of Response (DR)
Timepoint [8] 0 0
From the date of first documentation of OR to the date of the first documentation of PD or death due to any cause, whichever occurred first
Secondary outcome [9] 0 0
Phase 2 of Sub-Study A: Time to Tumor Response (TTR)
Timepoint [9] 0 0
From the date of first dose of study treatment to the date of first documentation of objective response
Secondary outcome [10] 0 0
Phase 2 of Sub-Study A: Progression-Free Survival (PFS)
Timepoint [10] 0 0
From the date of first dose of study treatment to the date of first documentation of PD or death due to any cause, whichever occurred first
Secondary outcome [11] 0 0
Phase 2 of Sub-Study A: Overall Survival (OS)
Timepoint [11] 0 0
From the date of first dose of study treatment to the date of death due to any cause or censoring date
Secondary outcome [12] 0 0
Phase 1b of Sub-Study A: Area Under the Concentration Verses Time Curve Over the Dosing Interval (AUCtau) After Single Dose of Sasanlimab
Timepoint [12] 0 0
Cycle 1 (pre-dose on Day 1, 168 hours [Day 8] and 336 hours [Day 15] and Day 28 post-dose)
Secondary outcome [13] 0 0
Phase 2 of Sub-Study A: Area Under the Concentration Verses Time Curve Over the Dosing Interval (AUCtau) After Single Dose of Sasanlimab
Timepoint [13] 0 0
Cycle 1 (pre-dose on Day 1, 336 hours [Day 15] and Day 28 post-dose)
Secondary outcome [14] 0 0
Phase 1b of Sub-Study A: Maximum Observed Plasma Concentration (Cmax) of Sasanlimab
Timepoint [14] 0 0
Cycle 1 (pre-dose on Day 1, 168 hours [Day 8],336 hours [Day 15] and Day 28 post-dose) and Cycle 5 (pre-dose on Day 1 and 168 hours [Day 8] post dose)
Secondary outcome [15] 0 0
Phase 2 of Sub-Study A: Maximum Observed Plasma Concentration (Cmax) of Sasanlimab
Timepoint [15] 0 0
Cycle 1 (pre-dose on Day 1, 336 hours [Day 15] and Day 28 post-dose) and Cycle 5 Day 1 (pre-dose)
Secondary outcome [16] 0 0
Phase 1b of Sub-Study A: Time for Cmax (Tmax) of Sasanlimab
Timepoint [16] 0 0
Cycle 1 (pre-dose on Day 1, 168 hours [Day 8], 336 hours [Day 15] and Day 28 post-dose) and Cycle 5 (pre-dose on Day 1 and 168 hours [Day 8] post dose)
Secondary outcome [17] 0 0
Phase 2 of Sub-Study A: Time for Cmax (Tmax) of Sasanlimab
Timepoint [17] 0 0
Cycle 1 (pre-dose on Day 1, 336 hours [Day 15] and Day 28 post-dose) and Cycle 5 Day 1 (pre-dose)
Secondary outcome [18] 0 0
Phase 1b of Sub-Study A: Pre-dose Concentration During Multiple Dosing (Ctrough) of Sasanlimab
Timepoint [18] 0 0
Cycle 5 Day 1 (pre-dose)
Secondary outcome [19] 0 0
Phase 2 of Sub-Study A: Pre-dose Concentration During Multiple Dosing (Ctrough) of Sasanlimab
Timepoint [19] 0 0
Cycle 5 Day 1 (pre-dose)
Secondary outcome [20] 0 0
Phase 1b of Sub-Study A: Ctrough of Encorafenib
Timepoint [20] 0 0
Cycle 5 Day 1 (pre-dose)
Secondary outcome [21] 0 0
Phase 2 of Sub-Study A: Ctrough of Encorafenib
Timepoint [21] 0 0
Cycle 5 Day 1 (pre-dose)
Secondary outcome [22] 0 0
Phase 1b of Sub-Study A: Ctrough of Binimetinib
Timepoint [22] 0 0
Cycle 5 Day 1 (pre-dose)
Secondary outcome [23] 0 0
Phase 2 of Sub-Study A: Ctrough of Binimetinib
Timepoint [23] 0 0
Cycle 5 Day 1 (pre-dose)
Secondary outcome [24] 0 0
Phase 1b of Sub-Study A: Number of Participants With Positive Anti-Drug Antibody (ADA) and Neutralizing Antibody (NAb) Against Sasanlimab
Timepoint [24] 0 0
Pre-dose on Cycle 1 Day 1 until end of treatment (up to approximately 255 days); each cycle is about 28 days
Secondary outcome [25] 0 0
Phase 2 of Sub-Study A: Number of Participants With Positive Anti-Drug Antibody (ADA) and Neutralizing Antibody (NAb) Against Sasanlimab
Timepoint [25] 0 0
Pre-dose on Cycle 1 Day 1 until end of treatment; each cycle is about 28 days
Secondary outcome [26] 0 0
Phase 2 of Sub-Study A: Objective Response (OR) Rate by Programmed Death Ligand-1 (PD-L1) Expression at Baseline
Timepoint [26] 0 0
From the date of first dose of study treatment until the date of the first documentation of PD
Secondary outcome [27] 0 0
Phase 2 of Sub-Study A: Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (EORTC QLQ-C30) Score
Timepoint [27] 0 0
Baseline up to end of treatment
Secondary outcome [28] 0 0
Phase 2 of Sub-Study A: Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC), Quality of Life Questionnaire-Lung Cancer 13 (QLQ- LC13) Score
Timepoint [28] 0 0
Baseline up to end of treatment

Eligibility
Key inclusion criteria
Inclusion Criteria Umbrella Phase 1b & 2:

- Histologically or cytologically confirmed locally advanced/metastatic (Stage IIIB-IV)
NSCLC.

- At least one measurable lesion per RECIST v1.1 at Screening.

- ECOG Performance Status 0 or 1.

- Resolved acute effects of any prior therapy to baseline severity or CTCAE Grade =1.

- Adequate hepatic, renal, and bone marrow function.

Additional Inclusion Criteria for Sub-Study A Phase 1b &2:

-BRAFV600E mutation in tumor tissue or plasma as determined by a local laboratory PCR or
NGS assay and documented in a local pathology report.

Additional Inclusion Criteria for Sub-Study A Phase 1b only:

-Any line of therapy for locally advanced/metastatic NSCLC.

Additional Inclusion Criteria for Sub-Study A Phase 2 only:

-Previously untreated for locally advanced/metastatic NSCLC

Additional Inclusion Criteria for Sub-Study B Phase 1b only::

-Any line of therapy for locally advanced/metastatic NSCLC.

Additional Inclusion Criteria for Sub-Study B Phase 2 only:

- Previously untreated for locally advanced/metastatic NSCLC (Arms B1 & B2), or

- One or 2 prior lines of therapy for advanced/metastatic NSCLC (Arm B3), including
immune checkpoint inhibitor treatment + chemotherapy, and have progressed during or
after that therapy.

- PD-L1 TPS =1%
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion Criteria Umbrella Phase 1b &2:

- Active or prior autoimmune disease that might deteriorate when receiving an
immunostimulatory agent.

- Active non-infectious pneumonitis, pulmonary fibrosis, or known history of
immune-mediated pneumonitis.

- Active infection requiring systemic therapy.

- Clinically significant cardiovascular disease.

- Other malignancy within 2 years of first dose, with exceptions.

- Symptomatic brain metastasis, with exceptions.

Additional Exclusion Criteria for Sub-Study A Phase 1b&2:

- EGFR mutation, ALK fusion oncogene, or ROS1 rearrangement.

- Prior treatment with any BRAF inhibitor or MEK inhibitor.

Additional Exclusion Criteria for Sub-Study A Phase 2 only:

-Prior therapy with anti-PD-1, anti-PD-L1, or anti-PD-L2 agents.

Additional Exclusion Criteria for Sub-Study B Phase 1b&2:

-Documentation of any tumor-driving molecular alteration (eg, BRAF, EGFR, ALK)

Additional Exclusion Criteria for Sub-Study B Phase 2 only:

- Prior therapy with anti-PD-1, anti-PD-L1, or anti-PD-L2 agents.(Arms B1 & B2)

- Confirmed progressive disease on 1st or 2nd imaging tumor assessment after initiation
of therapy for advanced/metastatic NSCLC.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1/Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
10/11/2020
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
17/06/2024
Actual
Sample size
Target
Accrual to date
Final
34
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
Chris O'Brien Lifehouse - Camperdown
Recruitment hospital [2] 0 0
Concord Hospital - Concord
Recruitment hospital [3] 0 0
GenesisCare North Shore - St Leonards
Recruitment hospital [4] 0 0
North Shore Radiology and Nuclear Medicine - St Leonards
Recruitment hospital [5] 0 0
Austin Health - Heidelberg
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
2139 - Concord
Recruitment postcode(s) [3] 0 0
2065 - St Leonards
Recruitment postcode(s) [4] 0 0
3084 - Heidelberg
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Maryland
Country [5] 0 0
United States of America
State/province [5] 0 0
Massachusetts
Country [6] 0 0
United States of America
State/province [6] 0 0
Michigan
Country [7] 0 0
United States of America
State/province [7] 0 0
New Jersey
Country [8] 0 0
United States of America
State/province [8] 0 0
New York
Country [9] 0 0
United States of America
State/province [9] 0 0
Tennessee
Country [10] 0 0
Belgium
State/province [10] 0 0
Antwerpen
Country [11] 0 0
Belgium
State/province [11] 0 0
Gent
Country [12] 0 0
Belgium
State/province [12] 0 0
Leuven
Country [13] 0 0
Taiwan
State/province [13] 0 0
Taichung
Country [14] 0 0
Taiwan
State/province [14] 0 0
Taipei City
Country [15] 0 0
Taiwan
State/province [15] 0 0
Taipei
Country [16] 0 0
United Kingdom
State/province [16] 0 0
London
Country [17] 0 0
United Kingdom
State/province [17] 0 0
Newcastle upon Tyne

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Pfizer
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Phase 1b/Phase 2 Umbrella Study; open-label, multi-center, parallel group study.

Sasanlimab (a PD-1 antagonist monoclonal antibody) will be combined with a different targeted
therapy in each sub-study. Phase1b of each sub-study will evaluate the safety of the
combination and select the dose for the Phase 2 portion. Phase 2 of each sub-study will
evaluate the anti-tumor activity of the combination.

Sub-Study A is active, not recruiting, ongoing participants are still receiving treatment in
Phase 1, Phase 2 will not be initiated.

Sub-study B is complete. All participants have discontinued treatment and any additional
follow up required by protocol.
Trial website
https://clinicaltrials.gov/ct2/show/NCT04585815
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Pfizer CT.gov Call Center
Address 0 0
Pfizer
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries