Trial Title:
Neoadjuvant INBRX-106 (Hexavalent OX40 Agonist) in Combination With Pembrolizumab as a Chemotherapy-sparing Regimen for Stage II TNBC (Triple Negative Breast Cancer) Patients
NCT ID:
NCT06353997
Condition:
Triple Negative Breast Cancer
Conditions: Official terms:
Breast Neoplasms
Triple Negative Breast Neoplasms
Pembrolizumab
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Pembrolizumab
Description:
Drug will be delivered per standard-of-care as established by trial Keynote-522.
Arm group label:
Pembrolizumab + INBRX-106
Other name:
KEYTRUDA
Intervention type:
Drug
Intervention name:
INBRX-106
Description:
INBRX-106 is a hexavalent, recombinant humanized IgG1, OX40 agonist antibody that targets
the human OX40 receptor (TNFRSF4, UniProtKB: P43489). INBRX-106 is based on a sdAb
platform and, in detail, 3 identical humanized camelid heavy chain-only antibody binding
domains (VHHs) targeting OX40 are joined end-to-end and with an Fc based on human IgG1 to
create a molecule that homo-dimerizes into an antibody targeting a total of 6 OX40
receptors.
Arm group label:
Pembrolizumab + INBRX-106
Summary:
This is a Phase II trial to assess feasibility of pembrolizumab + INBRX-106 as a
chemotherapy-sparing neoadjuvant therapy. One therapeutic arm is being evaluated to
provide an informal comparison of pharmacodynamic and clinical effects of concurrent
dosing schedule.
Detailed description:
A Simon 2-stage design is implemented to minimize exposure if the treatment regimen is
futile. If feasibility is established with responses exceeding futility parameters, study
will expand to stage 2. Additional arms may be introduced in a protocol amendment.
Below shows the sample size required using Simon's 2-stage design, 80% power and 5%
one-sided significance level:
- Null hypothesis: <5% pCR
- Alternative hypothesis: >35% pCR
- Stage I n (r*): 6 (0)
- Stage I + II total n (r): 12 (2)
- Criteria: Minimax
- Minimum responses to proceed to stage II: 1
Note: r* and r represents the threshold for declaring futility, i.e. greater than r* or r
responses would be required to consider ongoing investigation.
The null hypothesis of 5% is based upon the assumption that virtually no subjects would
experience pCR if the therapy was not effective. The alternative hypothesis of 35% is
based upon the assumption that complete responses in the absence of chemotherapy in
approximately one-third of subjects would be clinically meaningful, encouraging further
development of the treatment paradigm.
If no responses are observed, a second feasibility run-in may be considered using a
biomarker enrichment strategy (such as with the 27-gene IO score).
The arm will be terminated from further development if an unacceptable proportion of
patients experience rapid clinical/radiographic progression (defined as progression of
disease, or clinical evidence of progression), or other toxicities that interfere with
curative-intent therapy, defined as >1/6 evaluable subjects in stage I or >2/12 in stage
II, evaluated for each arm. This is a Pocock-type stopping boundary that yields the
probability of cross the boundary at most 23% when the rate of dose-limiting toxicity is
equal to 10%.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Age ≥ 18 years, inclusive of all genders.
2. Have an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1.
3. Patients must have histologically confirmed TNBC (ER/PR ≤ 10% allowed, HER2- as
defined by ASCO guidelines). HER2 negative permitted to enroll as IHC 0, 1, or 2+
with negative ISH.
4. Primary breast tumor at least 2cm (at least clinical T2 based on pathology, imaging,
or clinical exam) and measurable by ultrasound.
5. No clinical evidence of regional nodal involvement (N0).
6. Multifocal/multicentric disease is allowed if all suspicious sites have been
biopsied and are consistent with TNBC OR, if in the opinion of the investigator, all
suspicious sites represent the same disease process and biopsy is not clinically
indicated.
7. No prior therapy of any kind for TNBC.
8. Willingness to undergo serial ultrasounds, serial biopsies, and blood draws.
9. Patients must have adequate organ function as defined below. Specimens must be
collected within 28 days prior to the start of study treatment.
- Absolute neutrophil count (ANC) ≥1500/µL
- Platelets ≥100 000/µL
- Hemoglobin ≥8.0 g/dL or ≥5.0 mmol/L
- Creatinine OR measured or calculated creatinine clearance (GFR can also be used
in place of creatinine or CrCl) ≤1.5 × ULN OR ≥30 mL/min for participant with
creatinine levels >1.5 × institutional ULN
- Total bilirubin ≤1.5 × ULN OR direct bilirubin ≤ULN for participants with total
bilirubin levels >1.5 × ULN. Patients with elevated LFTs that are suggestive of
Gilbert's disease (a benign process) are eligible.
- AST (SGOT) and ALT (SGPT) ≤2.5 × ULN
- International normalized ratio (INR) OR prothrombin time (PT) Activated partial
thromboplastin time (aPTT) ≤1.5 × ULN unless participant is receiving
anticoagulant therapy as long as PT or aPTT is within therapeutic range of
intended use of anticoagulants
- TSH and free T4 levels should be drawn within 14 days prior to start of
treatment. Patients must have adequate thyroid function as demonstrated by free
T4 values, regardless of TSH.
10. Fertile male patients and female patients of childbearing potential must agree to
avoid impregnating a partner or becoming pregnant, respectively. They must be
willing to employ highly effective contraception methods (with a failure rate of
less than 1% when used consistently and correctly) at least 28 days before the first
dose of study treatment until 4 months after the last dose of study treatment.
A woman is considered of childbearing potential following menarche and until
becoming post-menopausal unless permanently sterile. Permanent sterilization methods
include hysterectomy, bilateral salpingectomy, and bilateral oophorectomy.
Postmenopausal state is defined as no menses for 12 months without an alternative
medical cause.
Acceptable methods of contraception presented below are in compliance with the
Clinical Trial Facilitation and Coordination Group (CTFG) recommendations related to
contraception and pregnancy testing in clinical trials, Version 1.1 (September,
2020). However, if a contraception method listed below is restricted by local
regulations/guidelines, then it does not qualify as an acceptable method of
contraception in that country/region. Local guidelines should be followed.
- Combined (estrogen and progestogen containing) hormonal contraception
associated with inhibition of ovulation: Oral. Intravaginal. Transdermal.
- Progestogen-only hormonal contraception associated with inhibition of
ovulation: Oral. Injectable. Implantable.
- Intrauterine device (IUD).
- Intrauterine hormone-releasing system (IUS).
- Bilateral tubal occlusion.
- Vasectomized partner. (Only considered to be highly effective contraception if
he is the sole sexual partner of the female patient of childbearing potential
and if the vasectomized partner has received medical assessment of the surgical
success.)
- Sexual abstinence. (Only considered to be highly effective contraception if
defined as refraining from heterosexual intercourse during the entire period of
risk associated with the study treatments. The reliability of sexual abstinence
needs to be evaluated in relation to the duration of the clinical study and the
preferred and usual lifestyle of the patient and if considered acceptable by
local regulatory agencies and IRBs/IECs.
11. Pre-menopausal women must have a negative urinary or serum pregnancy test within 72
hours prior to start of treatment. If screening serum pregnancy test collected
outside of 72 hours prior to start of treatment, this may be accepted for
determination of eligibility, but must be re-checked prior to treatment C1D1. If the
urine test is positive or cannot be confirmed as negative, a serum pregnancy test
will be required. The following age-specific requirements apply:
- Women < 50 years of age are considered post-menopausal if they have been
amenorrhoeic for 12 months or more following cessation of exogenous hormonal
treatments and if they have luteinizing hormone and follicle-stimulating
hormone levels in the post-menopausal range for the institution or underwent
surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or
hysterectomy).
- Women ≥ 50 years of age are considered post-menopausal if they have been
amenorrhoeic for 12 months or more following cessation of all exogenous
hormonal treatments, had radiation-induced menopause with last menses >1 year
ago, had chemotherapy-induced menopause with last menses >1 year ago, or
underwent surgical sterilization (bilateral oophorectomy, bilateral
salpingectomy or hysterectomy).
12. TIL score > 1%.
Exclusion Criteria:
1. Bilateral breast cancer.
2. Prior malignancies that require ongoing active therapy or are at clinically
significant risk of systemic recurrence in the opinion of the investigator.
3. Suspicion for, or histologically confirmed metastatic disease.
4. Symptomatic primary tumor.
5. Primary tumor with potential for skin ulceration or invasion of the chest wall, or
with pain that would suggest rapid progression or imminent muscle/skin involvement
in the opinion of the enrolling investigator.
6. Prior therapy with an anti-PD-1, anti-PD-L1, or antiPDL2 agent or with an agent
directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA-4,
OX40, CD137). Patients who have received these agents more than 3 years prior for
other malignancies may be considered if they are not still at clinically significant
risk of systemic recurrence in the opinion of the investigator.
7. Known allergy or hypersensitivity to any of the study drugs or any of the study drug
excipients.
8. Diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in
dosing exceeding 10 mg daily of prednisone equivalent) or any other form of
immunosuppressive therapy within 7 days prior to the first dose of study drug.
9. Active autoimmune disease that has required systemic treatment in excess of
prednisone 10mg daily or equivalent in the past 2 years (i.e., with use of disease
modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy
(e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for
adrenal or pituitary insufficiency, etc.) is not considered a form of systemic
treatment and is allowed.
10. Received a live vaccine within 30 days prior to the first dose of study drug.
Examples of live vaccines include, but are not limited to, the following: measles,
mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus
Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for
injection are generally killed virus vaccines and are allowed; however, intranasal
influenza vaccines (e.g., FluMist®) are live attenuated vaccines and are not
allowed.
Additionally, COVID-19 vaccinations (including boosters) should not be scheduled
within 72 hours (before or after) of dosing days for INBRX-106 and pembrolizumab.
11. Participants with a condition requiring systemic treatment with either
corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive
medications within 14 days of study drug administration. Inhaled or topical steroids
and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in
the absence of active autoimmune disease.
12. Known psychiatric or substance abuse disorders that would interfere with cooperation
with the requirements of the trial.
13. Pregnant or breastfeeding.
14. History of (non-infectious) pneumonitis that required steroids or has current
pneumonitis.
15. History of allogenic tissue/solid organ transplantation.
16. Has active autoimmune disease that has required systemic treatment in the past 2
years (i.e., with use of disease modifying agents, corticosteroids, or
immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or
physiologic corticosteroid replacement therapy for adrenal or pituitary
insufficiency, etc.) is not considered a form of systemic treatment. Has a known
additional malignancy (other than their current breast cancer diagnosis) that is
progressing or has required active systemic treatment within the past 3 years.
Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of
the skin, or carcinoma in situ (e.g., breast carcinoma cervical cancer in situ) that
have undergone potentially curative therapy are not excluded. Has a diagnosis of
immunodeficiency or is receiving chronic systemic steroid therapy (in dosing
exceeding 10 mg daily of prednisone equivalent) or any other form of
immunosuppressive therapy within 7 days prior to the first dose of study drug.
17. History or current evidence of any condition, therapy, or clinically significant
laboratory abnormality that might confound the results of the study, interfere with
the subject's participation for the full duration of the study, or is not in the
best interest of the subject to participate, in the opinion of the treating
investigator.
18. Active infection requiring systemic therapy with the exception of UTI requiring oral
antibiotic therapy and prophylactic anti-viral therapy (e.g. Acyclovir).
19. Known history of Human Immunodeficiency Virus (HIV) infection.
20. Known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg]
reactive) or known active Hepatitis C virus (defined as HCV RNA [qualitative] is
detected) infection. Patients with naturally acquired immunity are allowed (i.e.
HBsAg(-); HBcAb(+); HBsAb(+/-). Note: no testing for Hepatitis B and Hepatitis C is
required unless mandated by local health authority.
21. Any known history of active TB (Bacillus Tuberculosis).
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Ellison Institute of Technology (EITM)
Address:
City:
Los Angeles
Zip:
90064
Country:
United States
Status:
Not yet recruiting
Contact:
Last name:
Reva Basho, MD
Phone:
310-272-7640
Facility:
Name:
Providence Portland Cancer Institute - Franz Clinic
Address:
City:
Portland
Zip:
97213
Country:
United States
Status:
Recruiting
Contact:
Last name:
Nicole Moxon, RN
Phone:
503-215-1979
Email:
canrsrchstudies@providence.org
Investigator:
Last name:
Alison Conlin, MD
Email:
Sub-Investigator
Investigator:
Last name:
Evelyn Brosnan, MD
Email:
Sub-Investigator
Investigator:
Last name:
Evie Hobbs, MD
Email:
Sub-Investigator
Investigator:
Last name:
Rui Li, MD, PhD
Email:
Sub-Investigator
Investigator:
Last name:
Sasha Stanton, MD, PhD
Email:
Sub-Investigator
Investigator:
Last name:
Zheng Topp, MD
Email:
Sub-Investigator
Investigator:
Last name:
Amy Hartman, NP
Email:
Sub-Investigator
Investigator:
Last name:
Kathleen Dronkowski, NP
Email:
Sub-Investigator
Investigator:
Last name:
Kimberlie Dame, NP
Email:
Sub-Investigator
Investigator:
Last name:
Molly Davis, NP
Email:
Sub-Investigator
Investigator:
Last name:
RaYoung Chung, NP
Email:
Sub-Investigator
Investigator:
Last name:
Roxanne Griswold, NP
Email:
Sub-Investigator
Facility:
Name:
Providence St. Vincent Medical Center
Address:
City:
Portland
Zip:
97225
Country:
United States
Status:
Recruiting
Contact:
Last name:
Nicole Moxon, RN
Phone:
503-215-1979
Email:
canrsrchstudies@providence.org
Investigator:
Last name:
David Page, MD
Email:
Principal Investigator
Facility:
Name:
Swedish Cancer Institute
Address:
City:
Seattle
Zip:
98104
Country:
United States
Status:
Not yet recruiting
Contact:
Last name:
Danielle File, MD
Phone:
206-386-3900
Start date:
September 5, 2024
Completion date:
June 2029
Lead sponsor:
Agency:
Providence Health & Services
Agency class:
Other
Collaborator:
Agency:
Inhibrx Biosciences, Inc
Agency class:
Industry
Source:
Providence Health & Services
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06353997
