The safety and efficacy of this agent(s), or use in this setting, has not been established or is subject to confirmation. For an agent(s) whose safety and efficacy has not been established or confirmed, future regulatory approval or commercial availability is not guaranteed.

Clinical Trial Details

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Thoracic Cancer

Sasanlimab

Sasanlimab is an investigational compound. Its safety and efficacy have not been established.

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)
Phase 1 /2
NCT04585815

Active Not-enrolling

Globe
Locations

United States, Australia, Belgium, Taiwan, United Kingdom

Study design

Participant Group/Arm

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.

Intervention/Treatment

DRUG: Sasanlimab Prefilled syringe

prefilled syringe

DRUG: Encorafenib

capsules

DRUG: Binimetinib

tablets

Participant Group/Arm

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.

Intervention/Treatment

DRUG: Sasanlimab

solution supplied in vials

DRUG: Axitinib

tablets

DRUG: SEA-TGT

solution in vials

Key eligibility criteria

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%

 

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.

Key dates

Study start date
  • November 2020
Estimated primary completion date
  • June 2024

Key endpoints

Primary Outcome Measures
Outcome Measure

Phase 1b of Sub-Study A: Percentage of Participants With Dose-Limiting Toxicities (DLT)

Measure Description

DLT=AEs in DLT observation period (OP) related to any study intervention:Grade (G)4 neutropenia;thrombocytopenia or anemia;febrile neutropenia;neutropenic infection;G3 thrombocytopenia with bleeding. Any G\>=3 toxicity (except transient G3 fatigue, local reactions/headache that resolved to G\2\*ULN;or ALT/AST\>5\*ULN; or TB\>3\*ULN. Missing 75% of planned doses during DLT OP due to treatment-related toxicities. AE not listed/DLT criteria outside DLT OP was DLT at discretion of sponsor and investigator.

Time Frame

Day 1 up to Day 28 of Cycle 1

Outcome Measure

Phase 2 of Sub-Study A: Durable Objective Response Rate (ORR)

Measure Description

Durable ORR was defined as percentage of participants with confirmed complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1 based on investigator assessment, lasting for at least 10 months from the date of first CR or PR until the date of the first documentation of disease progression (PD), death, or start of new anticancer therapy. CR was defined as complete disappearance of all target lesions with exception of nodal disease. All target nodes must decrease to normal size (short axis \

Time Frame

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 Measures:
Outcome Measure

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

Measure Description

An AE is any untoward medical occurrence in a participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. AEs will be graded by the investigator according to NCI CTCAE version 5.0; where Grade 1=mild, Grade 2=moderate, Grade 3=severe, Grade 4=life-threatening and Grade 5=death.

Time Frame

From the start of study treatment (Cycle1 Day1) up to 30 days after last dose of study treatment (approximately 44 months)

Outcome Measure

Phase 2 of Sub-Study A: Number of Participants With Adverse Events Graded According to NCI-CTCAE Version 5.0

Measure Description

An AE is any untoward medical occurrence in a participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. AEs were planned to be graded by the investigator according to NCI CTCAE version 5.0; where Grade 1=mild, Grade 2=moderate, Grade 3=severe, Grade 4=life-threatening and Grade 5=death.

Time Frame

From the start of study treatment (Cycle1 Day1) up to 30 days after last dose of study treatment

Outcome Measure

Phase 1b of Sub-Study A: Number of Participants With Laboratory Abnormalities

Measure Description

Following assessments will be performed: hematology: hemoglobin, platelet count, white blood cell (WBC) count, absolute neutrophils, absolute lymphocytes, absolute monocytes, absolute eosinophils, absolute basophils. Chemistry: alanine aminotransferase (ALT), aspartate aminotransferase (AST), bicarbonate or carbon dioxide (CO2), C-reactive protein (CRP), alkaline phosphatase, sodium, potassium, magnesium chloride, total calcium, total bilirubin, total protein, blood urea nitrogen (BUN) or urea, creatinine, creatinine clearance, uric acid, glucose (random), lactate dehydrogenase, albumin, phosphorus or phosphate, amylase, lipase.

Time Frame

From the start of study treatment (Cycle1 Day1) up to 30 days after last dose of study treatment (approximately 44 months)

Outcome Measure

Phase 2 of Sub-Study A: Number of Participants With Laboratory Abnormalities

Measure Description

Hematology and clinical chemistry parameters were planned to be assessed.

Time Frame

From the start of study treatment (Cycle1 Day1) up to 30 days after last dose of study treatment

Outcome Measure

Phase 1b of Sub-Study A: Durable Objective Response Rate

Measure Description

Durable ORR was defined as percentage of participants with confirmed CR or PR according to RECIST v1.1 based on investigator assessment, lasting for at least 10 months from the date of first CR or PR until the date of the first documentation of PD, death, or start of new anticancer therapy. CR was defined as complete disappearance of all target lesions with exception of nodal disease. All target nodes must decrease to normal size (short axis \

Time Frame

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)

Outcome Measure

Phase 1b of Sub-Study A: Objective Response Rate

Measure Description

Objective response rate is defined as percentage of participants with confirmed best overall response of CR or PR according to RECIST v1.1 from the date of first dose of study treatment until the date of the first documentation of PD. CR was defined as complete disappearance of all target lesions with the exception of nodal disease. All target nodes must decrease to normal size (short axis \

Time Frame

From the date of first dose of study treatment until the date of the first documentation of PD (approximately 44 months)

Outcome Measure

Phase 2 of Sub-Study A: Objective Response Rate

Measure Description

Objective response rate is defined as percentage of participants with confirmed best overall response of CR or PR according to RECIST v1.1 from the date of first dose of study treatment until the date of the first documentation of PD. CR was defined as complete disappearance of all target lesions with the exception of nodal disease. All target nodes must decrease to normal size (short axis \

Time Frame

From the date of first dose of study treatment until the date of the first documentation of PD

Outcome Measure

Phase 2 of Sub-Study A: Duration of Response (DR)

Measure Description

DR was defined for participants with confirmed objective response (OR) as time from date of first documentation of OR to the date of first documentation of PD or death (any cause), whichever occurred first. OR=CR or PR according to RECIST v1.1 based on investigator assessment. CR and PR must be confirmed by repeat assessments performed no \

Time Frame

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

Outcome Measure

Phase 2 of Sub-Study A: Time to Tumor Response (TTR)

Measure Description

TTR is defined for participants with confirmed objective response as the time from the date of first dose of study treatment to the date of first documentation of objective response (CR or PR) which was subsequently confirmed. CR=complete disappearance of all target lesions with exception of nodal disease. All target nodes must decrease to normal size (short axis \

Time Frame

From the date of first dose of study treatment to the date of first documentation of objective response

Outcome Measure

Phase 2 of Sub-Study A: Progression-Free Survival (PFS)

Measure Description

PFS is defined as the time 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. PD=20% increase in sum of diameters of target measurable lesions above smallest sum observed (over baseline if no decrease in sum was observed during therapy), with a minimum absolute increase of 5 mm.

Time Frame

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

Outcome Measure

Phase 2 of Sub-Study A: Overall Survival (OS)

Measure Description

OS is defined as the time from the date of first dose of study treatment to the date of death due to any cause. Participants last known to be alive were planned to be censored at the date of last contact.

Time Frame

From the date of first dose of study treatment to the date of death due to any cause or censoring date

Outcome Measure

Phase 1b of Sub-Study A: Area Under the Concentration Verses Time Curve Over the Dosing Interval (AUCtau) After Single Dose of Sasanlimab

Measure Description

AUCtau was defined as area under the plasma concentration time curve from time zero to the next dose.

Time Frame

Cycle 1 (pre-dose on Day 1, 168 hours [Day 8] and 336 hours [Day 15] and Day 28 post-dose)

Outcome Measure

Phase 2 of Sub-Study A: Area Under the Concentration Verses Time Curve Over the Dosing Interval (AUCtau) After Single Dose of Sasanlimab

Time Frame

Cycle 1 (pre-dose on Day 1, 336 hours [Day 15] and Day 28 post-dose)

Outcome Measure

Phase 1b of Sub-Study A: Maximum Observed Plasma Concentration (Cmax) of Sasanlimab

Time Frame

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)

Outcome Measure

Phase 2 of Sub-Study A: Maximum Observed Plasma Concentration (Cmax) of Sasanlimab

Time Frame

Cycle 1 (pre-dose on Day 1, 336 hours [Day 15] and Day 28 post-dose) and Cycle 5 Day 1 (pre-dose)

Outcome Measure

Phase 1b of Sub-Study A: Time for Cmax (Tmax) of Sasanlimab

Time Frame

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)

Outcome Measure

Phase 2 of Sub-Study A: Time for Cmax (Tmax) of Sasanlimab

Time Frame

Cycle 1 (pre-dose on Day 1, 336 hours [Day 15] and Day 28 post-dose) and Cycle 5 Day 1 (pre-dose)

Outcome Measure

Phase 1b of Sub-Study A: Pre-dose Concentration During Multiple Dosing (Ctrough) of Sasanlimab

Time Frame

Cycle 5 Day 1 (pre-dose)

Outcome Measure

Phase 2 of Sub-Study A: Pre-dose Concentration During Multiple Dosing (Ctrough) of Sasanlimab

Time Frame

Cycle 5 Day 1 (pre-dose)

Outcome Measure

Phase 1b of Sub-Study A: Ctrough of Encorafenib

Time Frame

Cycle 5 Day 1 (pre-dose)

Outcome Measure

Phase 2 of Sub-Study A: Ctrough of Encorafenib

Time Frame

Cycle 5 Day 1 (pre-dose)

Outcome Measure

Phase 1b of Sub-Study A: Ctrough of Binimetinib

Time Frame

Cycle 5 Day 1 (pre-dose)

Outcome Measure

Phase 2 of Sub-Study A: Ctrough of Binimetinib

Time Frame

Cycle 5 Day 1 (pre-dose)

Outcome Measure

Phase 1b of Sub-Study A: Number of Participants With Positive Anti-Drug Antibody (ADA) and Neutralizing Antibody (NAb) Against Sasanlimab

Measure Description

In this outcome measure, number of ADA-positive and NAb-positive participants has been presented. A participant was considered ADA (or NAb) positive if (1) baseline titer was missing or negative and participant had \>= 1 post-treatment positive titer (treatment-induced), or (2) positive titer at baseline and had a \>= \[4-fold dilution increase\] in titer (equivalent to 0.602 unit increase in logarithm to base 10 (log10) titer from baseline in \>= 1 post-treatment sample (treatment-boosted).

Time Frame

Pre-dose on Cycle 1 Day 1 until end of treatment (up to approximately 255 days); each cycle is about 28 days

Outcome Measure

Phase 2 of Sub-Study A: Number of Participants With Positive Anti-Drug Antibody (ADA) and Neutralizing Antibody (NAb) Against Sasanlimab

Time Frame

Pre-dose on Cycle 1 Day 1 until end of treatment; each cycle is about 28 days

Outcome Measure

Phase 2 of Sub-Study A: Objective Response (OR) Rate by Programmed Death Ligand-1 (PD-L1) Expression at Baseline

Measure Description

OR rate is defined as percentage of participants with CR or PR according to RECIST v1.1 based on investigator assessment. CR=complete disappearance of all target lesions with exception of nodal disease. All target nodes must decrease to normal size (short axis \

Time Frame

From the date of first dose of study treatment until the date of the first documentation of PD

Outcome Measure

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

Measure Description

EORTC QLQ-C30: consisted of 30 questions grouped into 5 functional scales (physical, role, cognitive, emotional, and social); a global health status/global quality of life scale; 3 symptom scales (fatigue, pain, nausea and vomiting); and 6 single items that assessed additional symptoms (dyspnea, appetite loss, sleep disturbance, constipation, and diarrhea), and financial impact. All scales and single item measures ranged in score from 0 to 100. Higher scores on the global health status/quality of life scale represent higher health status/quality of life. Higher scores on the functional scales represent higher levels of functioning. Higher scores on the symptom scales and single items represent a greater presence of symptoms or financial impact.

Time Frame

Baseline up to end of treatment

Outcome Measure

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

Measure Description

The EORTC QLQ-LC13 is the lung cancer specific module of the EORTC Quality of Life Questionnaire. The EORTC QLQ-LC13 consisted of 13 questions which included 1 multi-item scale and 9 single items assessing symptoms (dyspnea, cough, hemoptysis, and site specific pain), side effects (sore mouth, dysphagia, peripheral neuropathy, and alopecia), and pain medication use. The item scale ranged from 1 to 4 (1 = Not at all; 4 = Very Much) where the EORTC-QLQ-LC13 scoring algorithm was applied to convert to a 0 to 100 point scale where 100 is best quality of life (QOL), for comparability. Higher scores are reflective of a greater presence of symptoms.

Time Frame

Baseline up to end of treatment

Number of participants

34

Collaborators and investigators

Sponsor: Pfizer

Collaborator: None

This information is current as of April 5th 2024.