SPARTA: APL-101 Study of Subjects With NSCLC With c-Met EXON 14 Skip Mutations and c-Met Dysregulation Advanced Solid Tumors

Sponsor

Apollomics Inc. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT03175224

Collaborator

(none)

344

Enrollment

Locations

Arm

110.1

Anticipated Duration (Months)

3.6

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The primary Phase 1 purpose of this study was to assess overall safety, tolerability and recommended Phase 2 dose (RP2D) of APL-101.

The Phase 2 portion will assess efficacy of the dose determined in Phase 1 in individuals with Non-Small Cell Lung Cancer with c-Met EXON 14 Skip Mutations; individuals with cancers associated with c-Met amplifications; individuals with cancers associated with c-Met fusion

Condition or Disease	Intervention/Treatment	Phase
Solid Tumor Advanced Cancer Renal Cancer Gastric Cancer Gastroesophageal Junction Adenocarcinoma NSCLC Lung Cancer Brain Tumor Glioblastoma Multiforme	Drug: APL-101 Oral Capsules	Phase 1/Phase 2

Detailed Description

This is a Phase 1/2, multi-center, global, open-label, 2-part study with a Dose Escalation Segment and Dose and Disease Expansion Cohorts study of APL-101, a c-MET inhibitor, to determine the recommended Phase 2 dose (RP2D) and dose limiting toxicities for APL-101, and to obtain preliminary efficacy and target engagement data, in subjects with NSCLC and advanced malignancies with c-Met dysregulation.

c-MET dysregulation will be determined from historical results by molecular pre-screening evaluations to determine eligibility of enrollment for both the Dose Escalation Segment (Phase 1) and Dose and Disease Expansion Cohorts (Phase 2).

Dose escalation will occur until a protocol defined dose limited toxicity (DLT) occurs and a tentative maximum tolerated dose (MTD) is determined.

Once dose is determined, seven cohort groups will be further evaluated:

Cohort A-1: NSCLC EXON 14 skip mutation (c-Met naïve, 1L)
Cohort A-2: NSCLC EXON 14 skip mutation (c-Met naïve, 2/3L),
Cohort B: NSCLC EXON 14 skip mutation (c-Met experienced; progressed on prior c-Met inhibitor),
Cohort C: basket of tumor types except primary CNS tumors with c-Met high-level amplifications (MET inhibitor naive)
Cohort C-1:NSCLC harboring MET amplification and wild-type EGFR (MET inhibitor naive)
Cohort D: basket of tumor types except primary CNS tumors harboring c-Met fusions (MET inhibitor naive)
Cohort E: Primary CNS tumors with MET alterations (MET inhibitor naive)

Study Design

Study Type:

Interventional

Anticipated Enrollment :

344 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Intervention Model Description:

Phase 1: Subjects will be assigned to a dose level in the order of study entry. Treatment includes four planned dose levels (100 mg, 200 mg, 300 mg, and 400 mg). Phase 2: Subjects will receive RP2D at 400mg daily dose (200mg BID). In Cohort E, the dose may be increased up to 300 mg BID starting at C2D1.Subjects with prior IO therapy within 90 days of study drug start will start at 100mg BID.Phase 1: Subjects will be assigned to a dose level in the order of study entry. Treatment includes four planned dose levels (100 mg, 200 mg, 300 mg, and 400 mg). Phase 2: Subjects will receive RP2D at 400mg daily dose (200mg BID). In Cohort E, the dose may be increased up to 300 mg BID starting at C2D1.Subjects with prior IO therapy within 90 days of study drug start will start at 100mg BID.

Masking:

None (Open Label)

Masking Description:

Open Label

Primary Purpose:

Treatment

Official Title:

Phase 1 / 2 Multicenter Study of the Safety, Pharmacokinetics, and Preliminary Efficacy of APL-101 in Subjects With Non-Small Cell Lung Cancer With c-Met EXON 14 Skip Mutations and c-Met Dysregulation Advanced Solid Tumors

Actual Study Start Date :

Sep 27, 2017

Anticipated Primary Completion Date :

Mar 30, 2026

Anticipated Study Completion Date :

Nov 30, 2026

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Single-Arm APL-101 Oral Capsules	Drug: APL-101 Oral Capsules Phase 1 Subjects will be assigned to a dose level of APL-101 in the order of study entry. Treatment includes 28-day cycles at four planned dose levels (100mg, 200mg, 300mg and 400mg). Each treatment cycle is administered by daily oral capsules taken every 12 hours. Phase 2 Subjects will be given 400mg daily dose (200mg BID) of APL-101 capsules. Other Names: PLB-1001 CBI-3103 Bozitinib CBT-101 Vebreltinib

Arm

Intervention/Treatment

Experimental: Single-Arm

APL-101 Oral Capsules

Drug: APL-101 Oral Capsules

Phase 1 Subjects will be assigned to a dose level of APL-101 in the order of study entry. Treatment includes 28-day cycles at four planned dose levels (100mg, 200mg, 300mg and 400mg). Each treatment cycle is administered by daily oral capsules taken every 12 hours. Phase 2 Subjects will be given 400mg daily dose (200mg BID) of APL-101 capsules.

Other Names:

PLB-1001

CBI-3103

Bozitinib

CBT-101

Vebreltinib

Outcome Measures

Primary Outcome Measures

Estimate the maximum tolerated dose (MTD) and the incidence of DLTs in Phase 1 (Completed) [From the time of informed consent signature through Cycle 1 (28 days) completion]
Adverse events, serious adverse events, and dose limiting toxicities
Objective response rate (ORR = CR + PR) per blinded independent review committee (BIRC) based on RECIST v1.1 (or relevant criteria per tumor type) [From time of informed consent signature through completion of treatment (1 cycle = 28 days)]
Anti-tumor activity per RECIST v1.1 or relevant evaluation criteria per tumor type.

Secondary Outcome Measures

Median duration of response (DOR) per BIRC. [Approximately 2 years]
DOR per RECIST v1.1 or relevant evaluation criteria per tumor type.
ORR per investigator assessment based on RECIST v1.1. [Approximately 2 years]
ORR per RECIST v1.1 or relevant evaluation criteria per tumor type.
Median DOR per investigator assessment. [Approximately 2 years]
DOR per RECIST v1.1 or relevant evaluation criteria per tumor type.
Antitumor activity by clinical benefit rate (CR + PR + SD ≥ 4 cycles) based on RECIST v1.1 Median time to progression (TTP). [Approximately 2 years]
Benefit rate per RECIST v1.1 or relevant evaluation criteria per tumor type.
Median time to progression (TTP). [Approximately 2 years]
TTP per RECIST v1.1 or relevant evaluation criteria per tumor type.
Progression Free Survival (PFS) and overall survival (OS) at 6, 12, 18 and 24 months [Approximately 3 years]
PFS and OS per RECIST v1.1 or relevant evaluation criteria per tumor type.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Major Inclusion Criteria:

Able to understand and comply with study procedures, understand the risks involved, and provide written informed consent.
For Phase 1, histologically and / or cytological confirmed unresectable or metastatic solid malignancy, refractory to standard therapies with no more than three prior lines of therapy (Completed).
For Phase 2, seven cohorts will be enrolled:

Cohort A-1: NSCLC EXON 14 skip mutation (c-Met naïve) for first line treatment, Cohort A-2:

NSCLC EXON 14 skip mutation (c-Met naïve) pretreated subjects with no more than 3 lines of prior therapy, Cohort B: NSCLC EXON 14 skip mutation (c-Met experienced; radiographic progression on prior c-Met inhibitor), Cohort C: basket of tumor types with c-Met high level amplification (except Primary CNS tumors), Cohort C-1: NSCLC harboring MET amplification and wild-type epidermal growth factor receptor (EGFR) with no more than 3 lines of prior therapy (MET Naive), Cohort D: basket of tumor types except for primary CNS tumors harboring MET gene fusions (e.g., NSCLC, upper GI, colorectal, hepatobiliary cancer). Previously treated; or previously untreated but refused standard treatment, or if treatment was unavailable or unfeasible (≤ 3 prior lines in unresectable or metastatic setting). Met naive, Cohort E: Primary CNS tumors with MET alterations (single or co-occurred MET fusion including PTPRZ1-MET [ZM] fusion, MET Exon 14 skipping mutation, or MET amplification).Previously treated or previously untreated but refused standard treatment, or if treatment was unavailable or unfeasible (≤ 3 prior lines), Met naive.

Local/archival result (tissue and/or plasma) of a positive c-Met dysregulation is required (except in Cohort A-1 in the US and Cohort C-1).

In Phase 2, provision of either archival or a fresh tumor biopsy sample (if safe and feasible) either from the primary or a metastatic site is required for study entry for Cohorts A-1, A-2, C, C-1, and D.

Measurable disease according to relevant criteria (RECIST v1.1, RANO for CNS tumors, or other relevant criteria per tumor type).
Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 and/or Karnofsky Performance Scale (KPS) score.
For all prior anticancer treatment, including radiotherapy, chemotherapy or targeted agents or hormonal therapy, a duration of more than 30 days or 5 half-lives of the agents used, whichever is shorter, must have elapsed, and any encountered toxicity must have resolved to levels meeting all the other eligibility criteria prior to the first dose of study treatment. Palliative radiotherapy to non-target lesions should be completed within 2 weeks prior to APL-101 administration.
No planned major surgery within 4 weeks of first dose of APL-101
Expected survival (life expectancy) ≥ 3 months from C1D1.

Major Exclusion Criteria:

Hypersensitivity to APL-101, excipients of the drug product, or other components of the study treatment regimen.
Known actionable mutation/gene rearrangement of EGFR (except for Cohort C), ALK, ROS1, RET, NTRK, KRAS, and BRAF.
Unstable angina or myocardial infarction within 1 year prior to first dose of APL-101, symptomatic or unstable arrhythmia requiring medical therapy, history of congenital prolonged QT syndrome, prolonged QT interval corrected by Fridericia formula (QTcF) at screening (> 450 msec based on the average of 3 measurements), or concurrent treatment with a medication that is a known risk for prolonging the QT interval.
Unable to swallow orally administered medication whole.
Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter drug absorption (e.g., Crohn's, ulcerative colitis, active inflammatory bowel disease, uncontrolled nausea, vomiting, diarrhea, or malabsorption syndrome).

Symptomatic and/or neurologically unstable CNS metastases, or who require an increase in steroid dose to control CNS disease. Subjects who have been receiving a stable steroid dose for at least 2 weeks prior to C1D1 may be allowed.

Women who are breastfeeding.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Banner MD Anderson	Gilbert	Arizona	United States	85234
2	Mayo Clinic	Phoenix	Arizona	United States	85054
3	Loma Linda University Medical Center	Loma Linda	California	United States	92354
4	University of Southern California / Norris Comprehensive Cancer Center	Los Angeles	California	United States	90033
5	Cedars-Sinai Medical Center - Samuel Oschin Comprehensive Cancer Institute	Los Angeles	California	United States	90048
6	University of California, Los Angeles (UCLA) Ronald Reagan Medical Center	Los Angeles	California	United States	90095
7	Kaiser Permanente - CA	Riverside	California	United States	92505
8	St. Joseph Health	Santa Rosa	California	United States	95403
9	Kaiser Permanente - Vallejo	Vallejo	California	United States	94589
10	Christiana Hospital	Newark	Delaware	United States	19713
11	Florida Cancer Specialists - South	Fort Myers	Florida	United States	33908
12	Mayo Clinic	Jacksonville	Florida	United States	32224
13	Florida Hospital Cancer Institute	Orlando	Florida	United States	32803
14	Florida Cancer Specialists - North	Saint Petersburg	Florida	United States	33705
15	Florida Cancer Specialists	Tallahassee	Florida	United States	32308
16	Moffitt	Tampa	Florida	United States	33612
17	Florida Cancer Specialists	West Palm Beach	Florida	United States	33401
18	Maryland Oncology Hematology	Silver Spring	Maryland	United States	20904
19	Beth Israel Deaconess Medical Center	Boston	Massachusetts	United States	02215
20	Dana Farber Cancer Institute	Boston	Massachusetts	United States	02215
21	Mayo Clinic	Rochester	Minnesota	United States	55905
22	Park Nicollet Institute - Frauenshuh Cancer Center	Saint Louis Park	Minnesota	United States	55416
23	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
24	University of North Carolina	Chapel Hill	North Carolina	United States	27599
25	Cleveland Clinic	Cleveland	Ohio	United States	44195
26	The Ohio State University (OSU)	Columbus	Ohio	United States	43210
27	Penn State Milton S. Hershey Medical Center	Hershey	Pennsylvania	United States	17033
28	St. Francis Cancer Center	Greenville	South Carolina	United States	29607
29	Sarah Cannon and HCA Research Institute	Nashville	Tennessee	United States	37203
30	The Don & Sybil Harrington Cancer Center	Amarillo	Texas	United States	79106
31	Huntsman Cancer Institute	Salt Lake City	Utah	United States	84112
32	West Virginia University Cancer Institute	Morgantown	West Virginia	United States	26506
33	University of Wisconsin	Madison	Wisconsin	United States	53792
34	Flinders Medical Centre	Bedford Park	South Australia	Australia
35	Border Medical Oncology	Albury		Australia
36	Peninsula and Southeast Oncology	Frankston		Australia
37	St Vincents Hospital Melbourne	Melbourne		Australia
38	Sir Charles Gairdner Hospital	Nedlands		Australia
39	Calvary Central Districts Hospita	North Adelaide		Australia
40	Lady Davis Institute for Medical Research Jewish General Hospital	Montreal	Quebec	Canada
41	Cross Cancer Institute	Edmonton		Canada
42	McGill University Health Center - Research Institute	Montréal		Canada
43	Princess Margaret Hospital	Toronto		Canada
44	Cancer Care Manitoba	Winnipeg		Canada
45	Tampere University Hospital	Tampere		Finland
46	CHRU de Brest - Hôpital Morvan	Brest		France
47	CHRU de Lille	Lille		France
48	Centre Leon Berard	Lyon		France
49	Centre d'Essais Precoces en Cancerologie de Marseille	Marseille		France
50	Hopital Bichat - Claude Bernard - AP-HP	Paris		France
51	CHU Rennes - Hopital Pontchaillou	Rennes		France
52	Gustave Roussy	Villejuif		France
53	Orszagos Koranyi Pulmonologiai Intezet	Budapest		Hungary
54	Szent Borbala Korhaz	Tatabanya		Hungary
55	Torokbalinti Tudogyogyintezet	Torokbalint		Hungary
56	Azienda Ospedaliero Universitaria Policlinico G. Rodolico-San Marco - Presidio Ospedaliero G. Rodolico	Catania		Italy
57	Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori	Meldola		Italy
58	Istituto Europeo di Oncologia	Milano		Italy
59	IRCCS Ospedale San Raffaele	Milan		Italy
60	PanOncology Trials, LLC	Rio Piedras		Puerto Rico
61	Arkhangelsk Clinical Oncological Dispensary	Arkhangelsk		Russian Federation
62	JSC Group of companies Medsi	Otradnoye		Russian Federation
63	Private Medical Institution Euromedservice	Saint Petersburg		Russian Federation
64	Saint-Petersburg Clinical Research Center of Specialized Types of Medical Care (Oncology)	Saint Petersburg		Russian Federation
65	Ogarev Mordovia State University	Saransk		Russian Federation
66	JSC Current Medical Technologies	St. Petersburg		Russian Federation
67	Volgograd Regional Clinical Oncology Dispensary	Volgograd		Russian Federation
68	National Cancer Centre Singapore	Singapore		Singapore
69	Oncocare Cancer Centre	Singapore		Singapore
70	Tan Tock Seng Hospital	Singapore		Singapore
71	Hospital Germans Trias i Pujol	Badalona		Spain
72	Hospital Clinic Barcelona	Barcelona		Spain
73	Hospital del Mar	Barcelona		Spain
74	Institut Catala d'Oncologia - L'Hospitalet	Barcelona		Spain
75	Hospital General Universitario Gregorio Maranon	Madrid		Spain
76	Hospital Universitario 12 de Octubre	Madrid		Spain
77	Hospital Universitario Puerta de Hierro Majadahonda	Madrid		Spain
78	Hospital Universitario Ramon y Cajal	Madrid		Spain
79	Hospital Universitario Central de Asturias	Oviedo		Spain
80	Hospital Universitario Donostia	San Sebastián		Spain
81	Hospital Universitario Virgen del Rocio	Sevilla		Spain
82	Instituto Valenciano de Oncologia	Valencia		Spain
83	Taipei Medical University - Shuang Ho Hospital	New Taipei City		Taiwan
84	Taichung Veterans General Hospital	Taichung		Taiwan
85	Chi-Mei Hospital - Liouying Branch	Tainan		Taiwan
86	National Taiwan University Hospital	Taipei City		Taiwan
87	Taipei Medical University Hospital	Taipei		Taiwan
88	Linkou Chang Gung Memorial Hospital (CGMHLK)	Taoyuan City		Taiwan
89	City Hematology Center of Municipal Non-Profit Enterprise "City Clinical Hospital #4" DCC	Dnipropetrovs'k		Ukraine
90	Communal Non-commercial Enterprise of Kharkiv Regional Council Regional Clinical Specialized Dispensary of Radiation Protection of Population, Department of Surger	Kharkiv		Ukraine
91	State Institution V.T.Zaitsev Institute of General and Urgent Surgery of National Academy of Medical Sciences of Ukraine, Department of Purulent Surgery	Kharkiv		Ukraine
92	Kyiv Municipal Clinical Oncology Center	Kyiv		Ukraine
93	Imperial College Healthcare NHS Trust	London		United Kingdom
94	The Christie NHS Foundation Trust	Manchester		United Kingdom
95	Royal Marsden Hospital - Surrey	Surrey Quays		United Kingdom