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Brief Title: Study With Andes-1537 in Patients With Specific Types of Advanced Solid Tumor

Phase 1 Open-label Two-stage Safety and Tolerability Study With Subcutaneous Administration of Andes-1537 for Injection in Patients With Specific Types of Advanced Solid Tumors That Are Refractory To or No Available Standard Therapy

INTRODUCTION

  • Org Study ID: AB1537-002
  • Secondary ID: N/A
  • NTC ID: NCT03985072
  • Sponsor: Andes Biotechnologies

BRIEF SUMMARY


The study is a Phase 1 Open-label Two-stage, Safety and Tolerability Study with Cancer
Type-specific Cohorts, Evaluating Subcutaneous Administration of Andes-1537 for Injection in
Patients with Advanced Solid Tumors that are Refractory to Standard Therapy or For Which No
Standard Therapy Is Available. Patients with unresectable solid tumors that are refractory or
have failed standard therapy and are deemed non-eligible or intolerant to further therapy or
for which no standard therapy is available will be included in 6 cancer type-specific
parallel cohorts. The following tumor types will be evaluated for potential inclusion in each
cancer type-specific cohort: gallbladder & biliary tract carcinoma; cervical carcinoma;
colorectal carcinoma; gastric carcinoma; pancreatic carcinoma; and clear cell renal cancer.

DETAILED DESCRIPTION


After screening, 9 patients in each cancer type-specific cohort (gallbladder & biliary tract
carcinoma; cervical carcinoma; colorectal carcinoma; gastric carcinoma; pancreatic carcinoma;
and clear cell renal cancer) will enter stage 1. These patients will receive a dose of 400 mg
of Andes-1537 twice a week (BIW) for continuous cycles of 4 weeks that will be repeated until
the patients presents drug toxicity requiring treatment discontinuation or disease
progression. The safety and tolerability evaluation will be continuous during the study. The
efficacy evaluation will be done by analysis of the clinical objective response rate (ORR) by
Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria after patients complete
the first two cycles (8 weeks). Thereafter, clinical ORR will be assessed every 8 weeks.
Additionally, tumor-cell activity assessment will be performed in biopsy samples after the
patients complete the first 2 cycles (8 weeks). Tumor markers assessment according to the
type of tumor will be evaluated every 2 cycles and at the end of study (EOS) visit. As
predefined, and according with the decision of the Study Safety and Steering Committee, in
those cohorts where minimal clinical response criteria were met, 15 additional patients will
be recruited (total of 24 patients per cohort) for stage 2 of the study. Patients included in
stage 2 will receive the same treatment regimen described for stage 1 and will be followed
until the patients present disease progression or drug toxicity requiring treatment
discontinuation. Patients included in stage 2 will receive the same follow-up as patients in
stage 1.


  • Overall Status
    Recruiting
  • Start Date
    April 26, 2019
  • Phase
    Phase 1
  • Study Type
    Interventional

PRIMARY OUTCOMES

Primary Outcome 1 - Measure: Incidence of treatment-emergent adverse events (TEAEs) through stages 1 and 2 of the study

Primary Outcome 1 - Timeframe: Screening and during cycle treatment (each cycle 4 weeks) until study completion (approximately 24 weeks or earlier if patient discontinues from study)

CONDITION

  • Tumor
  • Solid
  • Gall Bladder Cancer
  • Cervical Cancer
  • Colorectal Cancer
  • Gastric Cancer
  • Pancreatic Cancer
  • Clear Cell Renal Cell Carcinoma

ELIGIBILITY


Inclusion Criteria:

1. Men and women 18 years of age or older.

2. Can understand and voluntarily sign an informed consent form (ICF) prior to any
study-related assessment or procedure, and are able to adhere to the study visit
schedule and other protocol requirements.

3. Patients with documented pathological evidence of advanced unresectable solid tumors
that are, in the opinion of their treating physician, refractory or have failed
standard therapy and are deemed non-eligible or intolerant to further therapy, or for
which no standard therapy is available will be enrolled in both stages of the study in
the following 6 cancer type-specific cohorts:

- Gallbladder & Biliary Tract Cancer: Histologically confirmed stage 4 or
unresectable stage 3b biliary tract & gallbladder adenocarcinoma with relapsed,
refractory or progressive disease, who cannot tolerate or is considered resistant
to platinum based chemotherapy for advanced disease such as cis-platinum and
gemcitabine.

- Cervical Cancer: Histologically confirmed stages 4 or 3b cervical cancer with
relapsed, refractory or progressive disease, who cannot tolerate or is considered
resistant to platinum based chemotherapy for advanced disease such as
cis-platinum/carboplatin and paclitaxel.

- Colorectal Cancer: Histologically confirmed stage 4 colorectal adenocarcinoma
with relapsed, refractory or progressive disease, who cannot tolerate or is
considered resistant to combined treatment with fluoropyrimidines and/or
oxaliplatin and/or irinotecan and/or epidermal growth factor 1 inhibitors
(depending on molecular profile) either as single agent or in combination
therapy, depending treating oncologist´s decision. Patients with Kirsten rat
sarcoma (KRAS)-neuroblastoma ras (NRAS) wild type should have progressed after
cetuximab or panitunumab unless contraindicated or not available.

- Gastric Cancer: Histologically confirmed stage 4 or recurrent gastric
adenocarcinoma with relapsed, refractory or progressive disease, who cannot
tolerate or has progressed after first and second line combined chemotherapy
regimens containing Epirubicin, cisplatin, 5-fluorouracil (FU)/ leucovorin,
oxaliplatin, irinotecan and/or docetaxel. Patients with Her2Neu positive cancer
will not be eligible.

- Pancreatic Cancer: Histologically confirmed stage 4 or recurrent pancreatic
adenocarcinoma with relapsed, refractory or progressive disease, who cannot
tolerate or is considered resistant to combined treatment with leucovorin
calcium, 5-FU, irinotecan and oxaliplatin (FOLFIRINOX) or Gemcitabine based
chemotherapy, depending on age and performance status.

- Clear Cell Renal Cancer: Histologically confirmed stage 4 or recurrent clear cell
renal carcinoma with relapsed, refractory or progressive disease, who cannot
tolerate or is considered resistant to standard therapy or for whom standard
therapy is not available. Standard therapy may include two treatment lines of a
tyrosine kinase inhibitor or a mechanistic target of rapamycin (mTOR) inhibitor
and/or Nivolumab or other immunotherapy treatment.

4. Have measurable disease by RECIST.

5. Have Eastern Cooperative Oncology Group (ECOG) performance status of ≥ 1.

6. Have life expectancy ≥ 12 weeks as judged by the investigator.

7. Have adequate organ function, confirmed by the following laboratory values obtained ≤
3 days prior to the first treatment:

- Absolute neutrophil count (ANC) ≥ 1.5 × 109/L

- Hemoglobin (Hgb) ≥ 9 g/dL

- Platelets ≥ 100 × 109/L

- Aspartate aminotransaminase (AST) and alanine aminotransaminase (ALT) ≥ 2.5 ×
upper limit of normal (ULN)

- Serum total bilirubin ≤ 2.0 × ULN

- Serum creatinine ≤ 1.5 × ULN (patients with Creatinine > 1,5 x ULN may be
considered to participate if estimated or measured creatinine clearance ≥ 60
mL/min)

- Prothrombin time (PT), activated partial thromboplastin time (aPTT) ≤ 1.5 ULN if
not on anticoagulation therapy (patients receiving anticoagulation therapy must
be in the therapeutic range and stable for ≥ 4 weeks prior to study entry)

8. Patients with accessible tumor tissue, susceptible to biopsies through procedures such
as colonoscopy, endoscopy, endocervical biopsy (among others), are required to provide
consent for two biopsies throughout the study, to analyze tumor biomarkers. The first
tumor biopsy will be performed in these patients in a timeframe of 28 days prior to
the initial administration of the investigational product Andes-1537. Alternatively,
pathological archived material may be used, if the biopsy was collected within a
period of two months prior to initiation of treatment and with no anti-cancer
treatment performed since the collection date. The second biopsy will be performed
after 2 cycles (8 weeks) of treatment. If no archival material is available, and only
one lesion is amenable for biopsy (and is the only target lesion), the Medical Monitor
should be consulted for subject eligibility. Tumor biopsies and tumor archival
material must be suitable for biomarker assessment as described in the Laboratory
Manual.

9. Female patients of childbearing potential must have a negative serum pregnancy test
and be using adequate contraception (defined below) prior to study entry and must
agree to continue to use adequate contraception from study entry through at least 6
months after discontinuation of study drug. Note: Options for adequate contraception
with a failure rate of <1% per year include: tubal ligation, male sterilization,
hormonal implants, established proper use of combined oral or injected hormonal
contraceptives, and certain intrauterine devices. Alternatively, two methods (e.g.,
two barrier methods such as a condom and cervical cap) may be combined to achieve a
failure rate of <1% per year. Barrier methods must always be supplemented with the use
of a spermicide. Abstinence is acceptable only if it is in line with the preferred and
usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation,
symptothermal or postovulation methods) and withdrawal are not acceptable methods of
contraception. Should a female patient or a female partner of a male patient become
pregnant or suspect she is pregnant while participating in the study or within 6
months following discontinuation of the study drug, the patient should inform the
investigator immediately.

Exclusion Criteria:

1. Have known central nervous system metastases.

2. Have unstable angina, clinically significant cardiac arrhythmia, New York Heart
Association Class 3 or 4 congestive heart failure, or prolonged QT interval corrected
(QTc) wave of greater than 470 ms.

3. Receiving treatment with any medication known to produce QT prolongation within 7 days
of study entry.

4. Have had prior systemic chemotherapy treatments or investigational modalities ≤ 5
half-lives (t1/2) or 4 weeks, whichever is shorter, prior to starting treatment with
Andes 1537 or who have not recovered from side effects, grade 2 or greater, of such
therapy (except alopecia).

5. Have received more than 2 previous lines of systemic antineoplastic treatment that
includes chemotherapeutic agents, target therapies, or immunotherapy considered as
standard treatments for the type of tumor that the patient has.

6. Have had major surgery ≤ 2 weeks prior to starting treatment with Andes-1537 or who
have not recovered from side effects of such surgery.

7. Are pregnant or breastfeeding.

8. Have had deep vein thrombosis (DVT) or venous thromboembolism within 6 weeks of study
entry. Patients are permitted to enter the study if they are receiving anticoagulation
therapy considered to be in the therapeutic range and are stable for ≥ 4 weeks prior
to study entry.

9. Have active uncontrolled bleeding or a known bleeding disorder.

10. Have any serious or unstable concomitant systemic conditions that are incompatible
with this clinical study, including but not limited to substance abuse, psychiatric
disturbance, or uncontrolled intercurrent illness (including active infection),
arterial thrombosis, or symptomatic pulmonary embolism.

11. Have a known sensitivity to any of the components of Andes-1537.

12. Are unable or unwilling to follow protocol instructions and requirements.

Gender: All

Minimum Age: N/A

Maximum Age: 18 Years

Healthy Volunteers: No

OFFICIAL INFORMATION

Name: Bernadita Mendez, PhD

Role: Study Director

Affiliation: Andes Biotechnologies

Overall Contact

Name: Bernadita Mendez, PhD

Phone: +56-9-77937509

Email: x.verdina@theraresearch.com

LOCATION

Facility Status Contact
Facility: Fundacion Arturo Lopez Perez
Santiago, Region Metropolitana 7500921
Chile 		Status: Recruiting Contact:
Beatriz Riquelme
+56-2-28205770
riquelmeb@falp.org
Facility: Centro de Cancer de Nuestra Senora de la Esperanza, Red de Salud UC CHRISTUS
Santiago, Region Metropolitana 8330032
Chile 		Status: Recruiting Contact:
Monique Moreau
+56-2-23456881
amoreau@uc.cl
Facility: Centro de Investigaciones Clinicas Vina del Mar
Vina del Mar, V Region De Valparaiso 2540364
Chile 		Status: Recruiting Contact:
Gina Castagneto
+56-3-23245375
gcastagneto@institutooncologico.cl

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