Study of Seribantumab in Adult Patients With NRG1 Gene Fusion Positive Advanced Solid Tumors

Sponsor

Elevation Oncology (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04383210

Collaborator

(none)

Enrollment

Locations

Arms

Anticipated Duration (Months)

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study is an open-label, international, multi-center, Phase 2 study in adult patients with recurrent, locally-advanced or metastatic solid tumors, which harbor the NRG1 gene fusion.

Condition or Disease	Intervention/Treatment	Phase
Locally Advanced Solid Tumor Metastatic Solid Tumor Pancreatic Cancer Lung Cancer Head and Neck Cancer Breast Cancer Kidney Cancer Colorectal Cancer Bladder Cancer Ovarian Cancer Sarcoma Gallbladder Cancer Bile Duct Cancer Esophageal Cancer Uterine Cancer Cholangiocarcinoma Prostate Cancer	Drug: Seribantumab	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

75 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

CRESTONE: A Phase 2 Study of Seribantumab in Adult Patients With Neuregulin-1 (NRG1) Fusion Positive Locally Advanced or Metastatic Solid Tumors

Actual Study Start Date :

Sep 29, 2020

Anticipated Primary Completion Date :

Aug 1, 2022

Anticipated Study Completion Date :

Jun 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cohort 1 A minimum of 55 adult advanced solid tumor patients harboring NRG1 gene fusions, who have received prior standard treatment, excluding prior ERBB-directed therapy. Seribantumab 1-h IV infusion at various doses once weekly, every 2 weeks and every 3 weeks, during the induction, consolidation and maintenance dosing phases, respectively.	Drug: Seribantumab Anti-HER3 monoclonal antibody
Experimental: Cohort 2 Up to 10 adult advanced solid tumor patients harboring NRG1 gene fusions, who have received prior standard treatment, including prior ERBB-directed therapy. Seribantumab 1-h IV infusion at various doses once weekly, every 2 weeks and every 3 weeks, during the induction, consolidation and maintenance dosing phases, respectively.	Drug: Seribantumab Anti-HER3 monoclonal antibody
Experimental: Cohort 3 Up to 10 adult advanced solid tumor patients harboring NRG1 gene fusions lacking an EGF-like domain, who have received prior standard treatment, which may have included prior ERBB-directed therapy. Seribantumab 1-h IV infusion at various doses once weekly, every 2 weeks and every 3 weeks, during the induction, consolidation and maintenance dosing phases, respectively.	Drug: Seribantumab Anti-HER3 monoclonal antibody

Arm

Intervention/Treatment

Experimental: Cohort 1

A minimum of 55 adult advanced solid tumor patients harboring NRG1 gene fusions, who have received prior standard treatment, excluding prior ERBB-directed therapy. Seribantumab 1-h IV infusion at various doses once weekly, every 2 weeks and every 3 weeks, during the induction, consolidation and maintenance dosing phases, respectively.

Drug: Seribantumab

Anti-HER3 monoclonal antibody

Experimental: Cohort 2

Up to 10 adult advanced solid tumor patients harboring NRG1 gene fusions, who have received prior standard treatment, including prior ERBB-directed therapy. Seribantumab 1-h IV infusion at various doses once weekly, every 2 weeks and every 3 weeks, during the induction, consolidation and maintenance dosing phases, respectively.

Drug: Seribantumab

Anti-HER3 monoclonal antibody

Experimental: Cohort 3

Up to 10 adult advanced solid tumor patients harboring NRG1 gene fusions lacking an EGF-like domain, who have received prior standard treatment, which may have included prior ERBB-directed therapy. Seribantumab 1-h IV infusion at various doses once weekly, every 2 weeks and every 3 weeks, during the induction, consolidation and maintenance dosing phases, respectively.

Drug: Seribantumab

Anti-HER3 monoclonal antibody

Outcome Measures

Primary Outcome Measures

Objective Response Rate [Up to 12 months]
The primary objective of this study is to determine the overall objective response rate (ORR) by independent radiologic review to single agent seribantumab in patients with NRG1 gene fusion positive advanced cancer according to RECIST 1.1

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

To be eligible for participation in the study, patients must meet the following inclusion criteria:

Locally-advanced or metastatic solid tumor with an NRG1 gene fusion identified through molecular assays, such as PCR, NGS (RNA or DNA) or FISH, by a CLIA-certified or similarly accredited laboratory
Availability of fresh or archived FFPE tumor sample to be submitted to a central laboratory for confirmation of NRG1 gene fusion status
Patients should have received a minimum of one prior standard therapy appropriate for their tumor type and stage of disease, progressed or been nonresponsive to these available therapies, with no further available curative therapy options
≥ 18 years of age
ECOG performance status (PS) 0, 1 or 2
Patients must have at least one measurable extra-cranial lesion as defined by RECIST v1.1
Adequate hepatic function defined as:
Serum AST and serum ALT < 2.5 × upper limit of normal (ULN), or AST and ALT < 5 × ULN if liver function abnormalities due to underlying malignancy
Total bilirubin < 2.0 ULN. Subjects with a known history of Gilberts Disease and an isolated elevation of indirect bilirubin are eligible
Adequate hematologic status, defined as:
Absolute neutrophil count (ANC) ≥1.5 × 109/L not requiring growth factor support for at least 7 days prior to Screening, and
Platelet count ≥100.0×109/L not requiring transfusion support for at least 7 days prior to Screening
Able to provide informed consent or have a legal representative able and willing to do so
Ability to comply with outpatient treatment, laboratory monitoring, and required clinic visits for the duration of study participation
Willingness of men and women of reproductive potential to observe conventional and effective birth control for the duration of treatment and for 3 months following study completion; this may include barrier methods such as condom or diaphragm with spermicidal gel.

Exclusion Criteria:

Known, actionable oncogenic driver mutation other than NRG1 fusion where available standard therapy is indicated
Life expectancy < 3 months
Pregnant or lactating
Prior treatment with ERBB3/HER3 directed therapy (Cohort 1 only)
Prior treatment with pan-ERBB or any ERBB/HER2/HER3 directed therapy (Cohort 1 only)
Symptomatic or untreated brain metastases (Note: Patients with asymptomatic brain metastases treated with radiation or surgery and without evidence of progression by imaging at screening are eligible to participate in the study. Patients requiring ongoing corticosteroids to treat brain metastases will not be eligible).
Received other investigational agent or anticancer therapy within 28 days prior to planned start of seribantumab or 5 half-lives, whichever is shorter
Prior to initiation of seribantumab treatment, patients must have recovered from clinically significant toxicities from prior anticancer or investigational therapy
Any other active malignancy requiring systemic therapy
Known hypersensitivity to any of the components of seribantumab or previous CTCAE grade 3 or higher hypersensitivity reactions to fully human monoclonal antibodies
Clinically significant cardiac disease, including symptomatic congestive heart failure, unstable angina, acute myocardial infarction within 12 months of planned first dose, or unstable cardiac arrhythmia requiring therapy (including torsades de pointes)
Active uncontrolled systemic bacterial, viral, or fungal infection
Patients who are not appropriate candidates for participation in this clinical study for any other reason as deemed by the investigator

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham	Birmingham	Alabama	United States	35294
2	HonorHealth	Scottsdale	Arizona	United States	85258
3	Compassionate Care Research Group Inc.	Fountain Valley	California	United States	92708
4	Pacific Shores Medical Group	Huntington Beach	California	United States	92648
5	Cedars-Sinai Medical Center	Los Angeles	California	United States	90048
6	University of California - Irvine Medical Center	Orange	California	United States	92868
7	University of Colorado Denver	Denver	Colorado	United States	80220
8	Medical Oncology Hematology Consultants	Newark	Delaware	United States	19713
9	Georgetown University	Washington	District of Columbia	United States	20007
10	AdventHealth Orlando	Orlando	Florida	United States	32806
11	Moffitt Cancer Center	Tampa	Florida	United States	33612
12	University Cancer And Blood Center	Athens	Georgia	United States	30607
13	Hawaii Cancer Care	Honolulu	Hawaii	United States	96813
14	Northwestern University	Chicago	Illinois	United States	60611
15	Massachusetts General Hospital Cancer Center	Boston	Massachusetts	United States	02114
16	Henry Ford	Detroit	Michigan	United States	48202
17	Metro Minnesota CCOP	Saint Louis Park	Minnesota	United States	55416
18	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
19	Nebraska Methodist Hospital	Omaha	Nebraska	United States	68114
20	Montefiore Medical Center	Bronx	New York	United States	10467
21	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
22	Levine Cancer Institute	Charlotte	North Carolina	United States	28204
23	The Ohio State University	Columbus	Ohio	United States	43210
24	Oregon Health and Science University	Portland	Oregon	United States	97239
25	Penn State Health Hershey Medical Center Cancer Institute	Hershey	Pennsylvania	United States	17033
26	Fox Chase Cancer Center	Philadelphia	Pennsylvania	United States	19111
27	Sanford Oncology Clinic	Sioux Falls	South Dakota	United States	57104
28	Sarah Cannon Research Institute	Nashville	Tennessee	United States	37203
29	Texas Oncology-Baylor Charles A. Sammons Cancer Center	Dallas	Texas	United States	75246
30	The University of Texas M.D. Anderson Cancer Center	Houston	Texas	United States	77030
31	Utah Cancer Specialists	Salt Lake City	Utah	United States	84106
32	Virginia Cancer Specialists	Fairfax	Virginia	United States	22031
33	Northwest Medical Specialties, PLLC	Tacoma	Washington	United States	98405
34	University of Wisconsin	Madison	Wisconsin	United States	53792
35	St. Vincent's Hospital	Sydney	New South Wales	Australia	2010
36	Peter MacCallum Cancer Centre	Melbourne	Victoria	Australia	3000
37	BC Cancer	Vancouver	British Columbia	Canada	V5Z 4E6
38	William Osler Health System	Brampton	Ontario	Canada	L6R 3J7