QUILT-3.049: NANT Triple Negative Breast Cancer (TNBC) Vaccine: Combination Immunotherapy in Subjects With TNBC Who Have Progressed on or After Anthracycline-based Chemotherapy

Phase 1

Withdrawn

• Conditions: Triple Negative Breast Cancer
• Interventions: Biological: avelumab; Biological: bevacizumab; Drug: capecitabine; Drug: cisplatin; Drug: cyclophosphamide; Drug: 5-Fluorouracil; Drug: Leucovorin; Drug: nab-paclitaxel; Drug: Lovaza; Radiation: Stereotactic Body Radiation Therapy; Biological: ALT-803; Biological: ETBX-011; Biological: ETBX-051; Biological: ETBX-061; Biological: GI-4000; Biological: GI-6207; Biological: GI-6301; Biological: haNK

• Registration Number: NCT03175666
• Lead Sponsor: ImmunityBio, Inc.

Brief Summary

This is a phase 1b/2 study to evaluate the safety and efficacy of metronomic combination therapy in subjects with metastatic or unresectable TNBC who have progressed on or after anthracycline-based chemotherapy or who have refused anthracycline-based chemotherapy.

Detailed Description

Treatment will be administered in 2 phases, an induction and a maintenance phase, as described below. Subjects will continue induction treatment for up to 1 year or until they experience progressive disease (PD) or experience unacceptable toxicity (not correctable with dose reduction), withdraw consent, or if the Investigator feels it is no longer in the subject's best interest to continue treatment. Those who have a complete response (CR) in the induction phase will enter the maintenance phase of the study. Subjects may remain on the maintenance phase of the study for up to 1 year. Treatment will continue in the maintenance phase until the subject experiences PD or unacceptable toxicity (not correctable with dose reduction), withdraws consent, or if the Investigator feels it is no longer in the subject's best interest to continue treatment.

Study Timeline

• Study First Submitted: 2017-05-31
• Study First Submitted QC: 2017-06-01
• Study First Posted: 2017-06-05
• Status Verified: 2017-10
• Study Start: 2017-12
• Primary Completion: 2019-01
• Study Completion: 2021-12-28
• Last Update Submitted: 2025-02-20
• Last Update Posted: 2025-02-21

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

1. Age ≥ 18 years.
2. Able to understand and provide a signed informed consent that fulfills the relevant Institutional Review Board (IRB) or Independent Ethics Committee (IEC) guidelines.
3. Histologically confirmed metastatic or unresectable TNBC that has either progressed on or after anthracycline-based chemotherapy or subject has refused anthracycline-based chemotherapy.
4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
5. Have at least 1 measurable lesion of ≥ 1.5 cm.
6. Must have a recent tumor biopsy specimen obtained following the conclusion of the most recent anticancer treatment. If a historic specimen is not available, the subject must be willing to undergo a biopsy during the screening period.
7. Must be willing to provide blood samples, and, if considered safe by the Investigator, a tumor biopsy specimen at 8 weeks after the start of treatment.
8. Ability to attend required study visits and return for adequate follow-up, as required by this protocol.
9. Agreement to practice effective contraception for female subjects of child-bearing potential and non-sterile males. Female subjects of child-bearing potential must agree to use effective contraception for up to 1 year after completion of therapy, and non-sterile male subjects must agree to use a condom for up to 4 months after treatment.

Exclusion Criteria

1. History of persistent grade 2 or higher (CTCAE Version 4.03) hematologic toxicity resulting from previous therapy.

2. Within 5 years prior to first dose of study treatment, any evidence of other active malignancies or brain metastasis except controlled basal cell carcinoma; prior history of prostate cancer that is not under active systemic treatment (except hormonal therapy) and with undetectable prostate-specific antigen (PSA) (< 0.2 ng/mL); and bulky (≥ 1.5 cm) disease with metastasis in the central hilar area of the chest and involving the pulmonary vasculature.

3. Serious uncontrolled concomitant disease that would contraindicate the use of the investigational drug used in this study or that would put the subject at high risk for treatment-related complications.

4. Systemic autoimmune disease (eg, lupus erythematosus, rheumatoid arthritis, Addison's disease, autoimmune disease associated with lymphoma).

5. History of organ transplant requiring immunosuppression.

6. History of or active inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis).

7. Requires whole blood transfusion to meet eligibility criteria.

8. Inadequate organ function, evidenced by the following laboratory results:

   1. White blood cell (WBC) count < 3,500 cells/mm3.
   2. Absolute neutrophil count < 1,500 cells/mm3.
   3. Platelet count < 100,000 cells/mm3.
   4. Hemoglobin < 9 g/dL.
   5. Total bilirubin greater than the upper limit of normal (ULN; unless the subject has documented Gilbert's syndrome).
   6. Aspartate aminotransferase (AST [SGOT]) or alanine aminotransferase (ALT [SGPT]) > 2.5 × ULN (> 5 × ULN in subjects with liver metastases).
   7. Alkaline phosphatase levels > 2.5 × ULN (> 5 × ULN in subjects with liver metastases, or > 10 × ULN in subjects with bone metastases).
   8. Serum creatinine > 2.0 mg/dL or 177 μmol/L.
   9. International normalized ratio (INR) or activated partial thromboplastin time (aPTT) or partial thromboplastin time (PTT) >1.5 × ULN (unless on therapeutic anti-coagulation).

9. Uncontrolled hypertension (systolic > 150 mm Hg and/or diastolic > 100 mm Hg) or clinically significant (ie, active) cardiovascular disease, cerebrovascular accident/stroke, or myocardial infarction within 6 months prior to first study medication; unstable angina; congestive heart failure of New York Heart Association grade 2 or higher; or serious cardiac arrhythmia requiring medication.

10. Dyspnea at rest due to complications of advanced malignancy or other disease requiring continuous oxygen therapy.

11. Positive results of screening test for human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV).

12. Current chronic daily treatment (continuous for > 3 months) with systemic corticosteroids (dose equivalent to or greater than 10 mg/day methylprednisolone), excluding inhaled steroids. Short-term steroid use to prevent IV contrast allergic reaction or anaphylaxis in subjects who have known contrast allergies is allowed.

13. Known hypersensitivity to any component of the study medication(s).

14. Subjects taking any medication(s) (herbal or prescribed) known to have an adverse drug reaction with any of the study medications.

15. Concurrent or prior use of a strong CYP3A4 inhibitor (including ketoconazole, itraconazole, posaconazole, clarithromycin, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, voriconazole, and grapefruit products) or strong CYP3A4 inducers (including phenytoin, carbamazepine, rifampin, rifabutin, rifapentin, phenobarbital, and St John's Wort) within 14 days before study day 1.

16. Concurrent or prior use of a strong CYP2C8 inhibitor (gemfibrozil) or moderate CYP2C8 inducer (rifampin) within 14 days before study day 1.

17. Participation in an investigational drug study or history of receiving any investigational treatment within 14 days prior to screening for this study, except for testosterone-lowering therapy in men with prostate cancer.

18. Assessed by the Investigator to be unable or unwilling to comply with the requirements of the protocol.

19. Concurrent participation in any interventional clinical trial.

20. Pregnant and nursing women.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Nant TNBC	cyclophosphamide	avelumab, bevacizumab, capecitabine, cisplatin, cyclophosphamide, 5-fluorouracil, leucovorin, nab-paclitaxel, lovaza, stereotactic body radiation therapy, ALT-803, ETBX-011, ETBX-051, ETBX-061, GI-4000, GI-6207, GI-6301, and haNK.
Nant TNBC	Lovaza	avelumab, bevacizumab, capecitabine, cisplatin, cyclophosphamide, 5-fluorouracil, leucovorin, nab-paclitaxel, lovaza, stereotactic body radiation therapy, ALT-803, ETBX-011, ETBX-051, ETBX-061, GI-4000, GI-6207, GI-6301, and haNK.
Nant TNBC	cisplatin	avelumab, bevacizumab, capecitabine, cisplatin, cyclophosphamide, 5-fluorouracil, leucovorin, nab-paclitaxel, lovaza, stereotactic body radiation therapy, ALT-803, ETBX-011, ETBX-051, ETBX-061, GI-4000, GI-6207, GI-6301, and haNK.
Nant TNBC	ALT-803	avelumab, bevacizumab, capecitabine, cisplatin, cyclophosphamide, 5-fluorouracil, leucovorin, nab-paclitaxel, lovaza, stereotactic body radiation therapy, ALT-803, ETBX-011, ETBX-051, ETBX-061, GI-4000, GI-6207, GI-6301, and haNK.
Nant TNBC	Stereotactic Body Radiation Therapy	avelumab, bevacizumab, capecitabine, cisplatin, cyclophosphamide, 5-fluorouracil, leucovorin, nab-paclitaxel, lovaza, stereotactic body radiation therapy, ALT-803, ETBX-011, ETBX-051, ETBX-061, GI-4000, GI-6207, GI-6301, and haNK.
Nant TNBC	capecitabine	avelumab, bevacizumab, capecitabine, cisplatin, cyclophosphamide, 5-fluorouracil, leucovorin, nab-paclitaxel, lovaza, stereotactic body radiation therapy, ALT-803, ETBX-011, ETBX-051, ETBX-061, GI-4000, GI-6207, GI-6301, and haNK.
Nant TNBC	GI-6207	avelumab, bevacizumab, capecitabine, cisplatin, cyclophosphamide, 5-fluorouracil, leucovorin, nab-paclitaxel, lovaza, stereotactic body radiation therapy, ALT-803, ETBX-011, ETBX-051, ETBX-061, GI-4000, GI-6207, GI-6301, and haNK.
Nant TNBC	GI-4000	avelumab, bevacizumab, capecitabine, cisplatin, cyclophosphamide, 5-fluorouracil, leucovorin, nab-paclitaxel, lovaza, stereotactic body radiation therapy, ALT-803, ETBX-011, ETBX-051, ETBX-061, GI-4000, GI-6207, GI-6301, and haNK.
Nant TNBC	5-Fluorouracil	avelumab, bevacizumab, capecitabine, cisplatin, cyclophosphamide, 5-fluorouracil, leucovorin, nab-paclitaxel, lovaza, stereotactic body radiation therapy, ALT-803, ETBX-011, ETBX-051, ETBX-061, GI-4000, GI-6207, GI-6301, and haNK.
Nant TNBC	nab-paclitaxel	avelumab, bevacizumab, capecitabine, cisplatin, cyclophosphamide, 5-fluorouracil, leucovorin, nab-paclitaxel, lovaza, stereotactic body radiation therapy, ALT-803, ETBX-011, ETBX-051, ETBX-061, GI-4000, GI-6207, GI-6301, and haNK.
Nant TNBC	ETBX-051	avelumab, bevacizumab, capecitabine, cisplatin, cyclophosphamide, 5-fluorouracil, leucovorin, nab-paclitaxel, lovaza, stereotactic body radiation therapy, ALT-803, ETBX-011, ETBX-051, ETBX-061, GI-4000, GI-6207, GI-6301, and haNK.
Nant TNBC	GI-6301	avelumab, bevacizumab, capecitabine, cisplatin, cyclophosphamide, 5-fluorouracil, leucovorin, nab-paclitaxel, lovaza, stereotactic body radiation therapy, ALT-803, ETBX-011, ETBX-051, ETBX-061, GI-4000, GI-6207, GI-6301, and haNK.
Nant TNBC	ETBX-061	avelumab, bevacizumab, capecitabine, cisplatin, cyclophosphamide, 5-fluorouracil, leucovorin, nab-paclitaxel, lovaza, stereotactic body radiation therapy, ALT-803, ETBX-011, ETBX-051, ETBX-061, GI-4000, GI-6207, GI-6301, and haNK.
Nant TNBC	avelumab	avelumab, bevacizumab, capecitabine, cisplatin, cyclophosphamide, 5-fluorouracil, leucovorin, nab-paclitaxel, lovaza, stereotactic body radiation therapy, ALT-803, ETBX-011, ETBX-051, ETBX-061, GI-4000, GI-6207, GI-6301, and haNK.
Nant TNBC	bevacizumab	avelumab, bevacizumab, capecitabine, cisplatin, cyclophosphamide, 5-fluorouracil, leucovorin, nab-paclitaxel, lovaza, stereotactic body radiation therapy, ALT-803, ETBX-011, ETBX-051, ETBX-061, GI-4000, GI-6207, GI-6301, and haNK.
Nant TNBC	ETBX-011	avelumab, bevacizumab, capecitabine, cisplatin, cyclophosphamide, 5-fluorouracil, leucovorin, nab-paclitaxel, lovaza, stereotactic body radiation therapy, ALT-803, ETBX-011, ETBX-051, ETBX-061, GI-4000, GI-6207, GI-6301, and haNK.
Nant TNBC	haNK	avelumab, bevacizumab, capecitabine, cisplatin, cyclophosphamide, 5-fluorouracil, leucovorin, nab-paclitaxel, lovaza, stereotactic body radiation therapy, ALT-803, ETBX-011, ETBX-051, ETBX-061, GI-4000, GI-6207, GI-6301, and haNK.
Nant TNBC	Leucovorin	avelumab, bevacizumab, capecitabine, cisplatin, cyclophosphamide, 5-fluorouracil, leucovorin, nab-paclitaxel, lovaza, stereotactic body radiation therapy, ALT-803, ETBX-011, ETBX-051, ETBX-061, GI-4000, GI-6207, GI-6301, and haNK.

Primary Outcome Measures

Name	Time	Method
Incidence of treatment-emergent adverse events (AEs) and serious AEs (SAEs), graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03.	1 year	Phase 1b primary endpoint (safety)
ORR by Immune-related response criteria (irRC )	1 year	Phase 2 primary endpoint (ORR by irRC)
Objective response rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1	1 year	Phase 2 primary endpoint (ORR by RECIST)

Secondary Outcome Measures

Name	Time	Method
ORR by RECIST Version 1.1	1 year	Phase 1b secondary endpoint (ORR by RECIST)
PFS by irRC	2 years	Phase 1b and 2 secondary endpoint (PFS by irRC)
ORR by irRC	1 year	Phase 1b secondary endpoint (ORR by irRC)
Patient-reported outcomes (PRO) using the Functional Assessment of Cancer Therapy (FACT) Breast Symptom Index (FBSI) questionnaire	2 years	Phase 1b and 2 secondary endpoint (PRO)
Disease control rate (DCR): confirmed complete response, partial response, or stable disease lasting for at least 2 months	2 months	Phase 1b and 2 secondary endpoint (DCR)
Progression-free survival (PFS) by RECIST Version 1.1	2 years	Phase 1b and 2 secondary endpoint (PFS by RECIST)
Overall survival (OS): time from the date of first treatment to the date of death (any cause)	2 years	Phase 1b and 2 secondary endpoint (OS)
Duration of response (DR): time from the date of first response (partial response (PR) or complete response (CR)) to the date of disease progression or death (any cause) whichever occurs first	2 years	Phase 1b and 2 secondary endpoint (DR)
Incidence of treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs), graded using the NCI CTCAE Version 4.03	1 year	Phase 2 secondary endpoint (AEs)