Trial Title:
A Study of TAVO412 in Patients with Cancer
NCT ID:
NCT05548634
Condition:
Cancer
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Active, not recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
TAVO412
Description:
Biologic
Arm group label:
Part 1 Cohort 0
Arm group label:
Part 1 Cohort 1
Arm group label:
Part 1 Cohort 2
Arm group label:
Part 1 Cohort 3
Arm group label:
Part 1 Cohort 4
Arm group label:
Part 1 Cohort 5
Arm group label:
Part 2 Cohorts
Summary:
TAVO412 Phase 1 is an open-label, non-randomized, 2-part Phase I study to examine the
safety, tolerability, pharmacokinetics/pharmacodynamics, and preliminary efficacy of
TAVO412. Part 1 will utilize a standard 3 + 3 design to determine the MTD/RP2D of TAVO412
in subjects with advanced or metastatic solid tumors who progressed on prior approved
standard of care therapy. Part 2 will further evaluate the safety, tolerability,
preliminary efficacy, pharmacokinetics (PK), and pharmacologic activity of TAVO412 in a
new set of subjects with advanced or metastatic gastric cancer, non-small cell lung
cancer (NSCLC), or subjects of other solid tumor types with best clinical responses
(e.g., CR > PR > SD) from Part 1 that progressed on prior approved standard of care
therapy.
Detailed description:
This is an open-label, non-randomized, Phase I study to determine the safety and
tolerability, define the MTD/RP2D, and assess the preliminary efficacy of TAVO412 in
subjects with advanced or metastatic solid tumors who progressed on prior approved
standard of care therapy. Subjects will receive TAVO412 at the tested dose intravenously
on Day 1 and 15 in Cycle 1 and will continue this bi-weekly treatment schedule for all
future cycles.
The study will be conducted in 2 parts:
- Part 1 - Dose Escalation will determine the MTD and/or RP2D of TAVO412, which
includes defining the optimal dose administration schedule.
- Part 2 - Cohort Expansion will evaluate the recommended dose and administration
schedule (MTD/RP2D) determined in Part 1 in a new set of subjects with advanced or
metastatic gastric cancer, non-small cell lung cancer (NSCLC), or subjects of other
solid tumor types with best clinical responses (e.g., CR > PR > SD) from Part 1 that
progressed on prior approved standard of care therapy.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Male/Female aged 18 (at the time of screening) or older.
2. Willingness to provide written informed consent for the study.
3. Locally relapsed or refractory disease; locally advanced disease must not be
amenable to resection with curative intent.
4. Subjects who have disease progression after treatment with available therapies that
are known to confer clinical benefit, or who are intolerant to treatment, or who
refuse standard treatment. There is no limit to the number of prior treatment
regimens.
5. Presence of measurable disease based on RECIST v1.1. Tumor lesions situated in a
previously irradiated area, or in an area subjected to other locoregional therapy,
are not considered measurable unless there has been demonstrated progression in the
lesion.
6. Part 1: Subjects with advanced or metastatic solid tumors who progressed, or
refused, or are considered not eligible, on prior approved standard of care therapy.
The following will also apply for Part 2 of the study.
1. Patients with NSCLC who have sensitizing EGFR mutations must have experienced
disease progression on prior EGFR TKIs while those with tumor cMET genomic
alterations or over-expression must have received prior anti-PD1 agents and
platinum-based chemotherapy either in combination or sequentially.
2. Patients with gastric cancer or gastroesophageal cancer must have received
prior cytotoxic chemotherapy and immune checkpoint inhibitor therapy, and where
indicated, also received prior HER2-drected therapy or other FDA-approved
targeted therapy.
3. Patients with colorectal cancer must have received fluoropyrimidine,
oxaliplatin, and irinotecan ± VEGF-targeting monoclonal antibodies as prior
therapy. Patients with RAS-wild type tumors should have received approved
anti-EGFR monoclonal antibody. Patients with MSI-high/dMMR colorectal cancer
must have received prior immune checkpoint inhibitor therapy
4. Patients with TNBC must have experienced disease progression on the following
as prior therapies:
5. Pembrolizumab plus chemotherapy (CPS ≥ 10%)
6. Sacituzumab
7. Trastuzumab-deruxtecan (HER2-low)
7. Part 2: A new set of subjects with advanced or metastatic gastric cancer, non-small
cell lung cancer (NSCLC), or subjects of other solid tumor types with best clinical
responses (e.g., CR > PR > SD) from Part 1 that progressed on prior approved
standard of care therapy.
1. For subjects with Gastric Cancer: histologically confirmed Gastric or
Gastro-Esophageal Junction Carcinoma (including adenocarcinoma arising from the
lower esophagus). If multiple eligible patients exist, preference will be given
to enroll subjects with cMet or EGFR mutations, over-expression, or gene
amplification.
2. For subjects with NSCLC: histologically or cytologically confirmed tumor must
be NSCLC with EGFR and/or cMet mutations, over-expression, or gene
amplification.
8. Part 2: Willingness to undergo pretreatment and on-treatment tumor biopsies (core or
excisional).
Note: A baseline biopsy obtained for other purposes (i.e., not a protocol-defined
procedure) before signing consent may be utilized if the subject has not had any
intervening systemic therapy from the time of the biopsy to the start of treatment
(i.e., Cycle 1 Day 1), and if a minimum of 20 slides or preferably 1 tissue block
can be submitted.
Note: If a subject is scheduled to have a tumor biopsy for the purposes of this
study and it is subsequently determined that tumor tissue cannot safely be obtained,
then the subject may still enroll in the study. The subject may be replaced within
the cohort.
9. For both Part 1 & Part 2, subjects willing to consent to collection of additional
blood or tissue samples for exploratory biomarker or genomic analysis purposes.
10. ECOG performance status 0 or 1.
11. Female subjects of child-bearing potential (defined as women who have not undergone
surgical sterilization with a hysterectomy and/or bilateral oophorectomy and are not
postmenopausal, defined as ≥ 12 months of amenorrhea) must have a negative serum
pregnancy test at screening.
1. All female subjects of child-bearing potential must agree to take appropriate
precautions to avoid pregnancy (with at least 99% certainty) from screening
through 60 days after the last dose of study drug.
2. All male subjects must agree to take appropriate precautions to avoid pregnancy
with a partner (with at least 99% certainty) from screening through 90 days
after the last dose of study drug. Permitted methods that are at least 99%
effective in preventing pregnancy (see Appendix A) should be communicated to
the subjects and their understanding confirmed.
12. Patients with prior malignancies of the same or different tumor type and patients
with concurrent malignancies of the same or different tumor type will be included
13. Patients with mild and moderate hepatic impairment (defined as the equivalent of
National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE)
grade 1 toxicity), as well as those with aspartate transaminase (AST) and alanine
transaminase (ALT) elevations defined as grade 3 by the NCI CTCAE (> 5 to 20 x ULN
(upper limit of normal)), may be asymptomatic and able to tolerate doses equivalent
to patients with normal hepatic function
14. Patients with compromised renal function must meet creatinine clearance ≥ 30
mL/minute (estimated by the Cockcroft-Gault formula, [140 - age] × body
weight/plasma creatinine × 72 [× 0.85 if female])
15. Patients with Human Immunodeficiency Virus (HIV)/Hepatitis B (HBV)/Hepatitis C (HBC)
will be allowed to enter into the study provided the following criteria are met:
a) Patients with HIV infection must have CD4+ T-cell (CD4+) counts ≥ 350 cells/µL.
16. The following eligibility criteria are for patients with evidence of chronic HBV
infection or patients with history of chronic hepatitis C virus (HCV) or who are
virologically suppressed on HCV treatment:
1. Liver-related laboratory eligibility criteria should be the same as that for
the general population.
2. Exceptions: Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) and
bilirubin criteria may be less stringent in patients with cancers such as
hepatocellular carcinoma and cholangiocarcinoma in whom hepatic function based
on Child-Pugh score should be used.
3. Patients with chronic HBV infection with active disease who meet the criteria
for anti-HBV therapy should be on a suppressive antiviral therapy prior to
initiation of cancer therapy.
Note: Subjects with no prior history of hepatitis B infection who have been
vaccinated against hepatitis B and who have a positive antibody against
hepatitis B surface antigen test as the only evidence of prior exposure may
participate in the study.
4. Patients on concurrent HCV treatments must have HCV below the limit of
quantification.
5. Patients with untreated HCV may be enrolled if the HCV is stable, the patient
is not at risk for hepatic decompensation, and the investigational cancer
treatment is not expected to exacerbate the HCV infection.
17. Patients without a history of AIDS-defining opportunistic infections or no
opportunistic infection within the past 12 months. With the exception of:
1. Patients with a history of AIDS-defining cancers (e.g., Kaposi's sarcoma,
aggressive B-cell lymphoma, and invasive cervical cancer).
2. Patients on prophylactic antimicrobials where there may be drug-drug
interactions or overlapping toxicities should if appropriate, be changed to an
alternative antimicrobial, or if not, be excluded.
18. To ensure that effective antiretroviral therapy is tolerated and that toxicities are
not confused with investigational drug toxicities, trial participants should be on
established ART for at least four weeks and have an HIV viral load less than 400
copies/mL prior to enrollment. However, exclusion may be based on specific ART drugs
with overlapping toxicity.
Exclusion Criteria:
1. Laboratory and medical history parameters not within the protocol-defined range. If
the screening laboratory tests below were conducted > 7 days before treatment
initiation, they will need to be repeated on Day 1 before initiation of treatment.
1. Absolute neutrophil count < 1.5 × 109/L.
2. Platelets < 100 × 109/L.
3. Hemoglobin < 9 g/dL or < 5.6 mmol/L.
4. Creatinine clearance < 30 mL/minute (estimated by the Cockcroft-Gault formula,
[140 - age] × body weight/plasma creatinine × 72 (× 0.85 if female)
5. Aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase
≥ 2.5 × ULN.
Note: Subjects with 1) bone metastases and 2) no hepatic parenchymal metastases
on screening radiographic examinations may enroll if the alkaline phosphatase ≤
5 × ULN. Subjects with 1) bone metastases and/or 2) hepatic parenchymal
metastases on screening radiographic examinations may enroll if the alkaline
phosphatase is ≤ 5 × ULN only with medical monitor approval.
6. Total bilirubin ≥ 1.5 × ULN unless conjugated bilirubin ≤ ULN (note: conjugated
bilirubin only needs to be tested if total bilirubin exceeds ULN). If there is
no institutional ULN, then direct bilirubin must be < 40% of total bilirubin.
7. International normalized ratio, prothrombin time, or activated partial
thromboplastin time > 1.5 × ULN.
2. Transfusion of blood products (including platelets or red blood cells) or
administration of colony stimulating factors (including granulocyte
colony-stimulating factor, granulocyte macrophage colony- stimulating factor, or
recombinant erythropoietin) within 14 days before study Day 1.
3. Receipt of anti-cancer medications or investigational drugs within the following
intervals before the first administration of study drug:
1. ≤ 14 days for chemotherapy, targeted small molecule therapy, or radiation
therapy. Subjects must also not require chronic use of corticosteroids and must
not have had radiation pneumonitis as a result of treatment. A 1-week washout
is permitted for palliative radiation to non-central nervous system (CNS)
disease with sponsor approval.
Note: Bisphosphonates and denosumab are permitted concomitant medications.
2. ≤ 28 days for prior immunotherapy or persistence of active cellular therapy
(i.e., chimeric antigen receptor T-cell therapy; other cellular therapies must
be discussed with medical monitor to determine eligibility).
3. ≤ 28 days for a prior monoclonal antibody used for anticancer therapy with the
exception of denosumab.
4. ≤ 7 days for immune-suppressive-based treatment for any reason. Note: Use of
inhaled or topical steroids or corticosteroid use for radiographic procedures
is permitted.
Note: The use of physiologic corticosteroid replacement therapy may be approved
after consultation with the medical monitor.
5. ≤ 28 days or 5 half-lives (whichever is longer) before the first dose for all
other investigational agents or devices. For investigational agents with long
half-lives (e.g., > 5 days), enrollment before the fifth half-life requires
medical monitor approval.
4. Has not recovered to ≤ Grade 1 from toxic effects of prior therapy (including prior
immunotherapy) and/or complications from prior surgical intervention before starting
therapy.
Note: Subjects with stable chronic AEs (≤ Grade 2) not expected to resolve (such as
neuropathy and alopecia) are exceptions and may enroll with medical monitor
approval.
Note: Subjects with a history of any grade immune-related ocular AEs will be
excluded.
Note: Subjects with a history of a Grade 3 or higher immune-related AE from prior
immunotherapies are excluded from the dose escalation portion of the study.
5. Receipt of a live vaccine within 30 days of planned start of study drug. Note:
Examples of live vaccines include, but are not limited to, the following: measles,
mumps, rubella, chicken pox/zoster, yellow fever, rabies, Bacillus Calmette-Guérin,
and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed
virus vaccines and are allowed; COVID booster vaccines are permitted ≥ 4 weeks post;
however, intranasal influenza vaccines are live attenuated vaccines and are not
allowed.
6. Active autoimmune disease that required systemic treatment in the past (i.e., with
use of disease-modifying agents, corticosteroids, or immunosuppressive drugs).
Note: Subjects who have not required systemic treatment in the past 2 years should
discuss their case with medical monitor to determine eligibility.
Note: Subjects with hyper/hypothyroidism are eligible to participate. Note:
Replacement and symptomatic therapies (e.g., levothyroxine, insulin, or physiologic
corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) are
not considered a form of systemic treatment and are allowed.
7. Known active CNS metastases and/or carcinomatous meningitis. Note: Subjects with
previously treated brain metastases may participate provided that they are stable
(without evidence of progression by imaging for at least 28 days before the first
dose of study drug and any neurologic symptoms have returned to baseline), have no
evidence of new or enlarging brain metastases or CNS edema, and have not required
steroids for at least 14 days before the first dose of study drug.
8. Evidence of active, noninfectious pneumonitis or history of interstitial lung
disease.
9. Active infection requiring systemic therapy, including COVID-19.
10. Known allergy or reaction to any component of study drug or formulation components.
11. Is a female who is pregnant or breast feeding, or expecting to conceive children
within the projected duration of the study, starting with the screening visit
through 60 days after the last dose of study drug OR;
12. Is a male who is expected to father children within the duration of the study,
starting with the screening visit through 90 days after the last dose of study drug.
13. Any condition that would, in the investigator's judgment, interfere with full
participation in the study, including administration of study drug and attending
required study visits; pose a significant risk to the subject; or interfere with
interpretation of study.
14. Inability to comprehend or unwillingness to sign the informed consent form (ICF).
15. Subject has a history of class III or IV congestive heart failure or severe
nonischemic cardiomyopathy, unstable or poorly controlled angina, myocardial
infarction, ventricular arrhythmia, or coronary/peripheral artery bypass graft
within the previous 6 months of starting study treatment. Furthermore, subject
should have no history of cerebrovascular accident, transient ischemic attack, or
symptomatic pulmonary embolism, or uncontrolled hypertension.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Tisch Cancer Center
Address:
City:
NYC
Zip:
10029
Country:
United States
Start date:
May 8, 2023
Completion date:
June 1, 2026
Lead sponsor:
Agency:
Tavotek Biotherapeutics
Agency class:
Industry
Source:
Tavotek Biotherapeutics
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05548634
