| Eligibility |
Inclusion Criteria:
1. Age =18 years at the time of informed consent.
2. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
3. Life expectancy =3 months.
4. Diagnosed with histologically confirmed locally advanced and nonresectable, or
metastatic disease.
Patients diagnosed with one of the following tumor types:
A. Urothelial carcinoma of the bladder B. NSCLC, Squamous or Non-Squamous C. TNBC D.
Cervical cancer E. MSS CRC
5. Have progressed on treatment with an anti-PD-1/PD-L1monoclonal antibody (mAb)
administered either as monotherapy, or in combination with other checkpoint inhibitors
or other therapies (cohort A, B or C) and have failed available standard of care
treatment or deemed inappropriate candidates for additional standard treatments by the
investigator. PD-1 treatment progression is defined by meeting all of the following
criteria:
For cohort A, B and C:
1. Has received at least 2 doses of an approved anti-PD-1/PD-L1 mAb.
2. Has demonstrated disease progression after PD-1/PD-L1 as defined by RECIST v1.1.
The initial evidence of disease progression (PD) is to be confirmed by a second
assessment no less than four weeks from the date of the first documented PD, in
the absence of rapid clinical progression. i,ii
3. Progressive disease has been documented within 12 weeks from the last dose of
anti-PD-1/L1 mAb.
i. Seymour et al; iRECIST: Guidelines for response criteria for use in trials testing
immunotherapeutics. Lancet Oncol 18: e143-52 ii. This determination is made by the
investigator. Once PD is confirmed, the initial date of PD documentation will be
considered the date of disease progression.
For cohort B (NSCLC):
1. Prior treatments must include an anti-PD-1/PD-L1 mAb AND a platinum-based
chemotherapy.
2. Must include anti-PD-1/PD-L1 mAb or platinum-based chemotherapy was used in one
of the following settings:
- Locally advanced and unresectable
- Metastatic disease
- Adjuvant setting with disease progression occurred within 6 months after the
last dose
3. Must include anti-PD-1/PD-L1 mAb or platinum-based chemotherapy was used in one
of the following settings:
- Locally advanced and unresectable
- Metastatic disease
- Adjuvant setting with disease progression occurred within 6 months after the
last dose or with no prior anti-PD-1/PD-L1 therapy and failed standard of
care treatment (cohorts C, D, or E).
6. For cohorts A, C, D and E: Have received no more than 3 prior lines of systemic
therapy for advanced disease. Prior therapy in an adjuvant or neoadjuvant setting is
not considered as a prior line of systemic therapy. For cohort B (NSCLC), there is no
limitation to the number of prior lines of systemic therapy.
7. Have measurable disease per RECIST 1.1 as assessed by the local site investigator
and/or radiologist. Lesions situated in a previously irradiated area are considered
measurable if progression has been demonstrated in such lesions.
8. Have provided signed informed consent for the trial
9. Have provided archival tumor tissue sample obtained after anti-PD-1/PD-L1 or newly
obtained core or excisional biopsy of a tumor lesion not previously irradiated.
Formalin fixed, paraffin embedded (FFPE) tissue blocks are preferred to slides. Newly
obtained biopsies are preferred to archived tissue.
10. Left ventricular ejection fraction (LVEF) greater than 50% on echocardiography or
multiple gated acquisition (MUGA) scan.
11. Have adequate organ function.
12. Willing and able to comply with all aspects of the protocol
13. A female participant is eligible to participate if she is not pregnant, not
breastfeeding, and at least one of the following conditions applies:
1. Not a woman of childbearing potential Women are considered post-menopausal and
not of child-bearing potential if they have had 12 months of natural
(spontaneous) amenorrhea with an appropriate clinical profile (e.g., age
appropriate, history of vasomotor symptoms) or have had surgical bilateral
oophorectomy (with or without hysterectomy) at least six weeks prior to
Screening. In the case of oophorectomy alone, only when the reproductive status
of the woman has been confirmed by follow-up hormone level assessment is she
considered not of child-bearing potential.
2. Woman of childbearing potential who agrees to follow contraceptive guidance
during the treatment period and for at least 120 days after the last dose of
study treatment.
Highly effective contraception is defined as either:
- Total abstinence: When this is in line with the preferred and usual lifestyle of
the patient. (Periodic abstinence [e.g., calendar, ovulation, symptothermal,
post-ovulation methods] and withdrawal are not acceptable methods of
contraception.)
- Female sterilization: When the female study patient has had surgical bilateral
oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks
before taking study treatment. In case of oophorectomy alone, only when the
reproductive status of the woman has been confirmed by follow-up hormone level
assessment.
- Male partner sterilization (with the appropriate post-vasectomy documentation of
the absence of sperm in the ejaculate). For female study patients, the
vasectomized male partner should be the sole partner for that patient.
- Using a combination of any two of the following:
- Placement of an intrauterine device (IUD) or intrauterine system (IUS), and
- Barrier methods of contraception: condom or occlusive cap (diaphragm or
cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal
suppository.
- Hormonal contraception methods (e.g., oral, injected, implanted).
14. A male participant must agree to use contraception during the treatment period and for
at least 120 days after the last dose of study treatment.
Exclusion Criteria:
1. Have been discontinued treatment due to a Grade 3 or higher immune-related (irAE) from
prior anti-PD-1or anti-PD-L1, or with an agent directed to another stimulatory or
co-inhibitory T-cell receptor (eg, CTLA-4, OX 40, CD137)
2. Have received prior systemic anti-cancer therapy including investigational agents
within 4 weeks or 5 half-lives, whichever is shorter prior to treatment.
Note: Participants must have recovered from all AEs due to previous therapies to
=Grade 1 or returned to baseline. Participants with =Grade 2 neuropathy may be
eligible.
3. Have received prior radiotherapy within 2 weeks of start of study treatment.
Participants must have recovered from all radiation-related toxicities, not require
corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted
for palliative radiation (=2 weeks of radiotherapy) to non-CNS disease.
4. Have 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. Non live
COVID vaccinations or boosters should not occur during Cycle 1 or within 30 days prior
to the first dose of study drug.
5. Are currently participating in or have participated in a study of an investigational
agent or have used an investigational device within 4 weeks prior to the first dose of
study treatment.
Note: Participants who have entered the follow-up phase of an investigational study
may participate as long as it has been at least 4 weeks after the last dose of the
previous investigational agent.
6. Have had an allogenic tissue/solid organ transplant.
7. Have 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.
8. With a history of another primary malignancy within the past 2 years, with the
exception of basal or squamous cell skin cancer, or carcinoma in situ of the cervix or
breast that has undergone potentially curative therapy.
9. Have known active CNS metastases and/or carcinomatous meningitis. Participants with
previously treated brain metastases may participate provided they are radiologically
stable, i.e., without evidence of progression for at least 4 weeks by repeat imaging
(note that the repeat imaging should be performed during study screening), clinically
stable and without requirement of steroid treatment for at least 14 days prior to
first dose of study treatment.
10. Have known severe hypersensitivity to study treatment components.
11. Have an 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)
is not considered a form of systemic treatment and is allowed.
12. Participants with inflammatory bowel disease.
13. Have a history of (non-infectious) pneumonitis that required steroids or have current
pneumonitis.
14. Have an active infection requiring systemic therapy.
15. Participants with known human immunodeficiency virus (HIV) and/or history of Hepatitis
B or C infections, or known to be positive for Hepatitis B antigen (HBsAg)/ Hepatitis
B virus (HBV) DNA or Hepatitis C Antibody or RNA. Active Hepatitis C is defined by a
known positive Hep C Ab result and known quantitative HCV RNA results greater than the
lower limits of detection of the assay.
16. Prolongation of corrected QT [QTcF (Fridericia's corrected QT interval)] interval to
greater than 480 msec when electrolytes balance is normal.
17. Significant cardiovascular impairment: history of congestive heart failure greater
than New York Heart Association (NYHA) Class II, uncontrolled arterial hypertension,
unstable angina, myocardial infarction, or stroke within 6 months of the first dose of
study drug; or cardiac arrhythmia requiring medical treatment (including oral
anticoagulation).
18. Major surgery within 4 weeks before the first dose of study drug. Note: If a
participant received major surgery, they must have recovered adequately from surgery
and the toxicity and/or complications requiring the intervention prior to starting
study treatment.
19. Inability to take oral medication, or malabsorption syndrome or any other uncontrolled
gastrointestinal condition (eg, nausea, diarrhea, or vomiting) that might impair the
bioavailability of AN0025.
20. Have a history or current evidence of any condition, therapy, or laboratory
abnormality that might confound the results of the study, interfere with the
participant's participation for the full duration of the study, or is not in the best
interest of the participant to participate, in the opinion of the treating
investigator.
21. Have a known psychiatric or substance abuse disorder that would interfere with the
participant's ability to cooperate with the requirements of the study.
22. Is pregnant or breastfeeding or expecting to conceive or father children within the
projected duration of the study, starting with the screening visit through 120 days
after the last dose of study treatment.
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