NCT02981108

A Study to Evaluate Safety, PK and Efficacy of HS-10296 in Patients With NSCLC

Status unknown Phase 1, PHASE2 Results posted Last updated 23 January 2023

What this trial tests

Phase 1, PHASE2 trial testing HS-10296 in Nonsmall Cell Lung Cancer in 364 participants. Status unknown.

Timeline

8 May 2017

Primary endpoint
5 January 2019

31 March 2023

Quick facts

Lead sponsor	Jiangsu Hansoh Pharmaceutical Co., Ltd.
Phase	Phase 1, PHASE2
Status	Status unknown
Study type	INTERVENTIONAL
Allocation	non randomized
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	364
Start date	8 May 2017
Primary completion	5 January 2019
Estimated completion	31 March 2023
Sites	10 locations across United States

Drugs / interventions tested

• HS-10296 — full drug profile →

Conditions studied

• Nonsmall Cell Lung Cancer — all drugs for Nonsmall Cell Lung Cancer →

Sponsor

Jiangsu Hansoh Pharmaceutical Co., Ltd. — full company profile →

Who can join

18 and older, any sex, with Nonsmall Cell Lung Cancer. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Participants With Dose Limiting Toxicity (DLT) Phase I Part Primary · 21 days

DLT is defined as one of the following HS-10296 related adverse event (AE) ：(1) Hematological toxicity ≥ Grade 4 neutropenia lasting more than 5 days, febrile neutropenia of any duration (absolute neutrophil count \[ANC\]) \< 1.0 × 109/L and fever ≥ 38.5°C), Grade 4 thrombocytopenia, Grade 3 thrombocytopenia with bleeding, any requirement for platelet transfusion, Grade 4 anemia (unexplained by underlying disease); (2)Non-hematological toxicity ≥ CTCAE Grade 3 including Infection (including febrile neutropenia), confirmed prolongation of QT interval corrected with Fridericia's (QTcF) (\> 500 m

Group	Value	95% CI
Escalation Cohort 1	0
Escalation Cohort 2	0
Escalation Cohort 3	1
Escalation Cohort 4	1

Overall Response Rate (ORR) Phase II Part Primary · From the date of first dose until the date of disease progression or withdrawal from study, approximately 15 months

ORR is defined as the percentage of patients with a complete response (CR) or partial response (PR) that was confirmed at a subsequent scan at least 6 weeks later, as assessed according to RECIST (Response Evaluation Criteria In Solid Tumors Criteria) version 1.1 for target lesions and assessed by CT/MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

Group	Value	95% CI
Phase 2 Extension	65.6	59.2 – 71.5

Incidence and Severity of Adverse Events (AEs) Phase I Part Primary · From the screening period to 28 days after treatment completion, approximately 16 months

An AE is the development of an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product. An undesirable medical condition can be symptoms (e.g., nausea, chest pain), signs (e.g., tachycardia, enlarged liver), or the abnormal results of an investigation (e.g., laboratory findings, ECG). Any deterioration of the disease under study and associated symptoms or findings should not be regarded as an AE as far as the deterioration can be anticipated. The AE

At least one adverse event

Group	Value	95% CI
Escalation Cohort 1	6
Escalation Cohort 2	6
Escalation Cohort 3	8
Escalation Cohort 4	6
Expansion Cohort 1	30
Expansion Cohort 2	32
Expansion Cohort 3	31

At least one adverse event of Grade 3 or greater

Group	Value	95% CI
Escalation Cohort 1	1
Escalation Cohort 2	1
Escalation Cohort 3	3
Escalation Cohort 4	3
Expansion Cohort 1	6
Expansion Cohort 2	8
Expansion Cohort 3	11

At least one serious adverse event

Group	Value	95% CI
Escalation Cohort 1	2
Escalation Cohort 2	1
Escalation Cohort 3	2
Escalation Cohort 4	3
Expansion Cohort 1	5
Expansion Cohort 2	6
Expansion Cohort 3	3

Area Under the Plasma Concentration Versus Time Curve (AUC) of HS-10296 and HAS-719 From Zero to the 24-Hour Sampling Time (AUC0-24) After Single Dose of HS-10296 Secondary · From pre-dose to 24 hours after single dose on Day 1 of Cycle 0

Area under the plasma concentration versus time curve from time zero to the 24-hour sampling time at which the concentration was at or above the lower limit of quantification (LLQ). AUC0-24 was to be calculated according to the mixed log-linear trapezoidal rule.

HS-10296

Group	Value	95% CI
Escalation Cohort 1	1740.1175	± 917.7303
Escalation Cohort 2	5250.2364	± 3345.8348
Escalation Cohort 3	8174.4312	± 8126.7012
Escalation Cohort 4	8038.9348	± 1648.4566

HAS-719

Group	Value	95% CI
Escalation Cohort 1	298.4934	± 131.6189
Escalation Cohort 2	696.4536	± 293.4756
Escalation Cohort 3	1152.1150	± 475.5067
Escalation Cohort 4	1564.3829	± 488.6330

Elimination Half-life(T1/2) of HS-10296 and HAS-719 Secondary · From pre-dose to 120 hours after single dose on Day 1 of Cycle 0

Elimination half-life is the time measured for the concentration to decrease by one half. Half-life calculated by natural log 2 divided by λz.

HS-10296

Group	Value	95% CI
Escalation Cohort 1	31.29	± 9.57
Escalation Cohort 2	30.62	± 9.34
Escalation Cohort 3	35.19	± 13.89
Escalation Cohort 4	34.81	± 9.76

HAS-719

Group	Value	95% CI
Escalation Cohort 1	49.75	± 10.70
Escalation Cohort 2	55.36	± 19.95
Escalation Cohort 3	63.75	± 29.83
Escalation Cohort 4	57.79	± 13.95

Css Max of HS-10296 and HAS-719 After Multiple Dose Secondary · From pre-dose to 21 days after multiple dose on Day 1 of Cycle 2

Observed maximum plasma concentration (Css max) after multiple dose of HS-10296 and HAS-719

HS-10296

Group	Value	95% CI
Escalation Cohort 1	164.5000	± 70.6222
Escalation Cohort 2	352.8333	± 102.7062
Escalation Cohort 3	762.0000	± 231.8888
Escalation Cohort 4	765.4000	± 285.2802
Expansion Cohort 1	197.9308	± 78.6513
Expansion Cohort 2	413.2751	± 194.0200
Expansion Cohort 3	552.0635	± 257.9572
Phase 2 Extension	352.5111	± 185.3279

HAS-719

Group	Value	95% CI
Escalation Cohort 1	55.3500	± 18.1391
Escalation Cohort 2	118.1333	± 26.9018
Escalation Cohort 3	276.1667	± 42.9391
Escalation Cohort 4	338.2000	± 119.3302
Expansion Cohort 1	62.9535	± 21.4094
Expansion Cohort 2	142.1545	± 49.4867
Expansion Cohort 3	221.9404	± 83.6900
Phase 2 Extension	118.3758	± 43.3468

AUCss of HS-10296 and HAS-719 After Multiple Dose of HS-10296 Secondary · From pre-dose to 21 days after multiple dose on Day 1 of Cycle 2

Area Under the Plasma Concentration Versus Time Curve at steady state (AUCss) of HS-10296 and HAS-719 after multiple dose of HS-10296

HS-10296

Group	Value	95% CI
Escalation Cohort 1	2488.0953	± 439.3443
Escalation Cohort 2	7000.2498	± 2832.8180
Escalation Cohort 3	11994.8801	± 3839.4164
Escalation Cohort 4	14101.8608	± 5294.1409
Expansion Cohort 1	3550.8674	± 1451.0173
Expansion Cohort 2	7098.0738	± 2826.1228
Expansion Cohort 3	10185.6761	± 4862.0070
Phase 2 Extension	6602.2491	± 3482.0499

HAS-719

Group	Value	95% CI
Escalation Cohort 1	983.7103	± 201.9267
Escalation Cohort 2	2691.7220	± 677.2407
Escalation Cohort 3	5458.2304	± 659.3078
Escalation Cohort 4	8154.0849	± 1144.0617
Expansion Cohort 1	1304.4143	± 429.1216
Expansion Cohort 2	2852.8083	± 820.1842
Expansion Cohort 3	4692.6023	± 1771.6881
Phase 2 Extension	2467.8527	± 892.5071

Overall Response Rate (Phase I Part) Secondary · From the date of first dose until the date of disease progression or withdrawal from study, approximately 15 months

ORR is defined as the percentage of patients with a complete response (CR) or partial response (PR) that was confirmed at a subsequent scan at least 6 weeks later, as assessed according to RECIST (Response Evaluation Criteria In Solid Tumors Criteria) version 1.1 for target lesions and assessed by CT/MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

Group	Value	95% CI
Escalation Cohort 1	50.0	11.8 – 88.2
Escalation Cohort 2	66.7	22.3 – 95.7
Escalation Cohort 3	37.5	8.5 – 75.5
Escalation Cohort 4	16.7	0.4 – 64.1
Expansion Cohort 1	60.0	40.6 – 77.3
Expansion Cohort 2	54.5	36.4 – 71.9
Expansion Cohort 3	41.9	24.5 – 60.9

Progression-free Survival (PFS) Secondary · From the date of enrollment until the date of disease progression or death from any cause, approximately 15 months

The PFS is defined as the time from date of first dosing until the date of objective disease progression as defined by Response Evaluation Criteria in Solid Tumors （RECIST） v1.1 or death (by any cause in the absence of progression) regardless of whether the patients withdraws from HS-10296 therapy or receives another anti-cancer therapy prior to progression. Progression is defined as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

Group	Value	95% CI
Escalation Cohort 1	11.2	3.0 – NA
Escalation Cohort 2	7.0	5.8 – 12.5
Escalation Cohort 3	5.5	1.1 – 8.4
Escalation Cohort 4	3.7	0.8 – 11.0
Expansion Cohort 1	9.6	6.7 – 15.1
Expansion Cohort 2	13.6	6.9 – 19.2
Expansion Cohort 3	11.1	8.3 – 24.8
Phase 2 Extension	12.4	9.7 – 15.0

Disease Control Rate (DCR) Secondary · From the date of first dose until the date of disease progression or withdrawal from study, approximately 15 months

Objective response is assessed by RECIST 1.1 thereby to evaluate disease control rate. The DCR is defined as the proportion of patients with a best overall response of CR, PR, or SD (stable disease).

Group	Value	95% CI
Escalation Cohort 1	100.0	54.1 – 100.0
Escalation Cohort 2	100.0	54.1 – 100.0
Escalation Cohort 3	75.0	34.9 – 96.8
Escalation Cohort 4	50.0	11.8 – 88.2
Expansion Cohort 1	83.3	65.3 – 94.4
Expansion Cohort 2	97.0	84.2 – 99.9
Expansion Cohort 3	93.5	78.6 – 99.2
Phase 2 Extension	93.4	89.6 – 96.2

Overall Survival (OS) Phase II Part Secondary · From the date of enrollment until the date of death from any cause, approximately 48 months

Overall survival will be assessed based on the date of first dose and survival status at the time of analysis. Overall survival is defined as the time from date of first dose until the documentation of death from any cause.

Group	Value	95% CI
Phase 2 Extension	31.5	25.9 – 35.7

Depth of Response (DepOR) Secondary · From the date of enrollment until the date of disease progression or death, approximately 15 months

Depth of Response (DepOR) Only in part II dose-extention phase. DepOR is defined as the percentage change in tumor size, based on longest diameter or reconstructed volume, observed at the lowest point compared with baseline.

Group	Value	95% CI
Phase 2 Extension	-47.89	± 22.333

Adverse events — posted to ClinicalTrials.gov

Time frame: Throughout the study, from informed consent until the end of the follow-up period. The follow-up period is defined as 28 ± 3 days after study treatment is discontinued, assessed up to 16 months. Deaths were assessed up to 48 months. Serious and Other (Non-Serious) Adverse Events were assessed up to 16 months.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Escalation Cohort 1

Serious: 2/6 (33%)

Deaths: 0/6

Escalation Cohort 2

Serious: 1/6 (17%)

Deaths: 0/6

Escalation Cohort 3

Serious: 2/8 (25%)

Deaths: 0/8

Escalation Cohort 4

Serious: 3/6 (50%)

Deaths: 0/6

Expansion Cohort 1

Serious: 5/30 (17%)

Deaths: 0/30

Expansion Cohort 2

Serious: 6/33 (18%)

Deaths: 0/33

Expansion Cohort 3

Serious: 3/31 (10%)

Deaths: 0/31

Phase 2 Extension

Serious: 30/244 (12%)

Deaths: 11/244

Serious adverse events (72 terms)

Reaction	System	Escalation Cohort 1	Escalation Cohort 2	Escalation Cohort 3	Escalation Cohort 4	Expansion Cohort 1	Expansion Cohort 2	Expansion Cohort 3	Phase 2 Extension
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—	—	—
Pneumonitis	Infections and infestations	—	—	—	—	—	—	—	—
Death	General disorders	—	—	—	—	—	—	—	—
Lung infection	Infections and infestations	—	—	—	—	—	—	—	—
Deep vein thrombosis	Vascular disorders	—	—	—	—	—	—	—	—
Pyrexia	General disorders	—	—	—	—	—	—	—	—
Haemoptysis	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—	—	—
Venous thrombosis limb	Vascular disorders	—	—	—	—	—	—	—	—
Blood creatine phosphokinase increased	Investigations	—	—	—	—	—	—	—	—
Platelet count decreased	Investigations	—	—	—	—	—	—	—	—
Fall	Injury, poisoning and procedural complications	—	—	—	—	—	—	—	—
Sepsis	Infections and infestations	—	—	—	—	—	—	—	—
Urinary tract infection	Infections and infestations	—	—	—	—	—	—	—	—
Dizziness	Nervous system disorders	—	—	—	—	—	—	—	—
Presyncope	Nervous system disorders	—	—	—	—	—	—	—	—
Anemia	Blood and lymphatic system disorders	—	—	—	—	—	—	—	—
Bowel obstruction	Gastrointestinal disorders	—	—	—	—	—	—	—	—
Peripheral swelling	General disorders	—	—	—	—	—	—	—	—
Interstitial lung disease	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—	—	—
Appendicitis	Infections and infestations	—	—	—	—	—	—	—	—
Biliary tract infection	Infections and infestations	—	—	—	—	—	—	—	—
Intervertebral discitis	Infections and infestations	—	—	—	—	—	—	—	—
Pyelonephritis acute	Infections and infestations	—	—	—	—	—	—	—	—
Atypical pneumonia	Infections and infestations	—	—	—	—	—	—	—	—
Bacteraemia	Infections and infestations	—	—	—	—	—	—	—	—

Other adverse events (115 terms — click to expand)

Reaction	System	Escalation Cohort 1	Escalation Cohort 2	Escalation Cohort 3	Escalation Cohort 4	Expansion Cohort 1	Expansion Cohort 2	Expansion Cohort 3	Phase 2 Extension
Aspartate aminotransferase increased	Investigations	—	—	—	—	—	—	—	—
Upper respiratory tract infection	Infections and infestations	—	—	—	—	—	—	—	—
Rash	Skin and subcutaneous tissue disorders	—	—	—	—	—	—	—	—
Alanine aminotransferase increased	Investigations	—	—	—	—	—	—	—	—
Pruritus	Skin and subcutaneous tissue disorders	—	—	—	—	—	—	—	—
Cough	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—	—	—
White blood cell count decreased	Investigations	—	—	—	—	—	—	—	—
Constipation	Gastrointestinal disorders	—	—	—	—	—	—	—	—
Proteinuria	Renal and urinary disorders	—	—	—	—	—	—	—	—
Nausea	Gastrointestinal disorders	—	—	—	—	—	—	—	—
Neutrophil count decreased	Investigations	—	—	—	—	—	—	—	—
Blood creatinine increased	Investigations	—	—	—	—	—	—	—	—
Leukopenia	Blood and lymphatic system disorders	—	—	—	—	—	—	—	—
Diarrhoea	Gastrointestinal disorders	—	—	—	—	—	—	—	—
Electrocardiogram QT prolonged	Investigations	—	—	—	—	—	—	—	—
Hyperuricaemia	Metabolism and nutrition disorders	—	—	—	—	—	—	—	—
Mouth ulceration	Gastrointestinal disorders	—	—	—	—	—	—	—	—
Weight increased	Investigations	—	—	—	—	—	—	—	—
Arthralgia	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—	—	—
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—	—	—
Stomatitis	Gastrointestinal disorders	—	—	—	—	—	—	—	—
Pain in extremity	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—	—	—
Dry eye	Eye disorders	—	—	—	—	—	—	—	—
Oedema peripheral	General disorders	—	—	—	—	—	—	—	—
Myalgia	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—	—	—
Urticaria	Skin and subcutaneous tissue disorders	—	—	—	—	—	—	—	—
Vision blurred	Eye disorders	—	—	—	—	—	—	—	—
Chest pain	General disorders	—	—	—	—	—	—	—	—
Liver injury	Hepatobiliary disorders	—	—	—	—	—	—	—	—
Paronychia	Infections and infestations	—	—	—	—	—	—	—	—
Weight decreased	Investigations	—	—	—	—	—	—	—	—
Rhinorrhoea	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—	—	—
Ventricular extrasystoles	Cardiac disorders	—	—	—	—	—	—	—	—
Xerosis	General disorders	—	—	—	—	—	—	—	—
Conjunctivitis	Infections and infestations	—	—	—	—	—	—	—	—
Blood lactate dehydrogenase increased	Investigations	—	—	—	—	—	—	—	—
Hypoproteinaemia	Metabolism and nutrition disorders	—	—	—	—	—	—	—	—
Eczema	Skin and subcutaneous tissue disorders	—	—	—	—	—	—	—	—
Sinus bradycardia	Cardiac disorders	—	—	—	—	—	—	—	—
Tachycardia	Cardiac disorders	—	—	—	—	—	—	—	—

Most-reported serious reactions: Pulmonary embolism, Pneumonitis, Death, Lung infection, Deep vein thrombosis, Pyrexia, Haemoptysis, Venous thrombosis limb.

Data from ClinicalTrials.gov NCT02981108 adverse events section.

Sponsor's own description

This is a Phase 1/2, open-label, multicenter study of HS-10296 with dose escalation, dose expansion and extension cohorts in locally advanced or metastatic non-small-cell lung cancer (NSCLC) patients who have progressed following prior therapy with an epidermal growth factor receptor(EGFR) tyrosine kinase inhibitor (TKI) agent. The study is designed to evaluate safety, tolerability, pharmacokinetics (PK), and anti-tumor activity of once-daily and orally (PO) administered HS-10296. The overall study design is shown in the flow chart below, which consists of 3 phases: dose escalation, dose expansion and extension cohort.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Management of acquired resistance to EGFR TKI-targeted therapy in advanced non-small cell lung cancer.
   Wu SG, Shih JY. · · 2018 · cited 577× · PMID 29455650 · DOI 10.1186/s12943-018-0777-1
2. Emerging therapeutic agents for advanced non-small cell lung cancer.
   Chen R, Manochakian R, James L, Azzouqa AG, et al · · 2020 · cited 244× · PMID 32448366 · DOI 10.1186/s13045-020-00881-7
3. Efficacy of Aumolertinib (HS-10296) in Patients With Advanced EGFR T790M+ NSCLC: Updated Post-National Medical Products Administration Approval Results From the APOLLO Registrational Trial.
   Lu S, Wang Q, Zhang G, Dong X, et al · · 2022 · cited 110× · PMID 34801749 · DOI 10.1016/j.jtho.2021.10.024
4. Therapeutic advances in non-small cell lung cancer: Focus on clinical development of targeted therapy and immunotherapy.
   Cheng Y, Zhang T, Xu Q. · · 2021 · cited 81× · PMID 34977873 · DOI 10.1002/mco2.105
5. Mechanisms of Acquired Resistance and Tolerance to EGFR Targeted Therapy in Non-Small Cell Lung Cancer.
   Chhouri H, Alexandre D, Grumolato L. · · 2023 · cited 67× · PMID 36672453 · DOI 10.3390/cancers15020504
6. Next-Generation <i>EGFR</i> Tyrosine Kinase Inhibitors for Treating <i>EGFR</i>-Mutant Lung Cancer beyond First Line.
   Sullivan I, Planchard D. · · 2016 · cited 67× · PMID 28149837 · DOI 10.3389/fmed.2016.00076
7. Emerging Targeted Therapies in Advanced Non-Small-Cell Lung Cancer.
   Li S, de Camargo Correia GS, Wang J, Manochakian R, et al · · 2023 · cited 47× · PMID 37296863 · DOI 10.3390/cancers15112899
8. The advance of the third‑generation EGFR‑TKI in the treatment of non‑small cell lung cancer (Review).
   Cheng Z, Cui H, Wang Y, Yang J, et al · · 2024 · cited 37× · PMID 38063215 · DOI 10.3892/or.2023.8675