Montag, 26. Juli 2021
Navigation öffnen
Anzeige:
Canakinumab
Canakinumab
 
JOURNAL ONKOLOGIE – STUDIE
KISIMA-01

Phase 1b Study to Evaluate ATP128, With or Without BI 754091, in Patients With Stage IV Colorectal Cancer

Rekrutierend

NCT-Nummer:
NCT04046445

Studienbeginn:
Juli 2019

Letztes Update:
16.06.2021

Wirkstoff:
ATP128, BI 754091

Indikation (Clinical Trials):
Colorectal Neoplasms, Neoplasm Metastasis, Rectal Neoplasms, Colonic Neoplasms

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
-

Sponsor:
Amal Therapeutics

Collaborator:
Boehringer Ingelheim

Studienleiter

Scott Kopetz
Principal Investigator
MD Anderson

Kontakt

Thomas Bogenrieder, PhD, MD
Kontakt:
Phone: + 41 22 594 39 53
E-Mail: thomas.bogenrieder@boehringer-ingelheim.com
» Kontaktdaten anzeigen

Studienlocations
(3 von 8)

Honor Health Institute
85258 Scottsdale
United StatesAktiv, nicht rekrutierend» Google-Maps
NYU Langone Health
10016 New York
United StatesRekrutierend» Google-Maps
Ansprechpartner:
Joseph Benson
E-Mail: Benson.Joseph@nyulangone.org

Garcia Chelsea
E-Mail: Chelsea.Garcia@nyulangone.org
» Ansprechpartner anzeigen
University of Texas, MD Anderson Cancer Center
77030 Houston
United StatesRekrutierend» Google-Maps
Ansprechpartner:
Edmund Scott Kopetz, MD
Phone: 713-792-2828
E-Mail: SKopetz@mdanderson.org
» Ansprechpartner anzeigen
Alle anzeigen

Studien-Informationen

Brief Summary:

This is a multi-center, non-randomised Phase 1b study to evaluate the safety and tolerability

of ATP128 alone or in combination with BI 754091.

ATP128 is a self-adjuvanted chimeric recombinant protein vaccine being developed in

combination with programmed cell death 1 (PD-1) blockade for the treatment of microsatellite

stable (MSS) patients not responding to PD-1 blockade. The PD-1 inhibitor being tested with

ATP128 is the BI 754091 compound which belongs to the human immunoglobulin G4 (IgG4) subclass

of antibodies.

The Sponsor plans to enrol 32 patients with histologically or cytologically confirmed stage

IV colorectal cancer coming form three different patient populations:

- Cohort 1a: 6 patients with stage IV colorectal cancer (CRC) having failed standard of

care (SoC) therapies

- Cohorts 1b, 2a: 11 patients with stage IV microsatellite stable/mismatch

repair-proficient (MSS/MMRp) CRC being in stable disease (SD) or partial response (PR)

after first line of SoC (6 months duration at minimum)

- Cohort 2b: 15 patients with stage IV MSS/MMRp hepatic-limited metastatic CRC

Patients eligible for this study will be enrolled in one of the 4 cohorts depending on their

disease:

- Patients in Cohort 1a will receive ATP128 as single agent

- Patients in Cohorts 1b, 2a will receive ATP128 in combination with BI 754091

- Patients in Cohorts 2b will receive ATP128 in combination with BI 754091 before and

after the liver surgery

Ein-/Ausschlusskriterien

Inclusion Criteria:

Cohort 1a

1. Ability to comprehend and willingness to provide written informed consent (ICF) for

the study.

2. Age ≥ 18 years.

3. Patient with histologically or cytologically confirmed stage IV CRC who has failed

standard therapies.

4. Must have received Standard of Care systemic treatment consisting of fluoropyrimidin-

oxaliplatin and/or irinotecan based therapy for stage IV CRC disease.

5. Presence of at least 1 measurable lesion by computed tomography or magnetic resonance

imaging per RECIST v1.1 as determined by the local site investigator/radiologist

assessment.

6. Presence of at least one liver lesion amenable to repeated biopsy, ideally not the one

being used for measuring.

7. Willingness to undergo two fresh liver biopsies (pre-treatment and on-treatment).

8. Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2 (see Appendix 1).

9. Life expectancy of at least 3 months.

10. Resolution of all toxicities and any toxic effect(s) of the most recent prior therapy

to Grade 1 or less (except alopecia). Patients with ≤ Grade 2 neuropathy and Grade ≤ 2

fatigue are an exception and may enroll.

11. Adequate renal, hepatic, and hematologic functions as defined by laboratory parameters

≤ 7 days before study treatment initiation.

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

13. Absolute lymphocyte count ≥ 0.5 × 109/L.

14. Platelets ≥ 100 × 109/L.

15. Hemoglobin level ≥ 9 g/dL.

16. Measured or calculated creatinine clearance (glomerular filtration rate can also be

used in place of creatinine clearance) ≥ 50 mL/min according to the formula of

Cockcroft-Gault (see Appendix 6).

17. Total bilirubin ≤ 1.5 × upper limit of normal (ULN); if total bilirubin is > 1.5 x ULN

then direct bilirubin must be ≤ 1.5 × ULN. Patients with known Gilbert's Syndrome may

enroll if total bilirubin ≤ 3 × ULN.

18. Alanine aminotransferase/aspartate aminotransferase (ALT/AST) ≤ 2.5 × ULN or ≤ 5 x ULN

in patients with hepatic involvement.

19. A female patient is eligible to participate if she is not pregnant (see Appendix 2),

not breastfeeding, and at least one of the following conditions applies:

Not a woman of childbearing potential (WOCBP) as defined in Appendix 2. OR A WOCBP who

agrees to use highly effective contraceptive methods as outlined in Appendix 2 during

the treatment period and for at least 180 days after the last dose of study treatment

and refrain from egg donation during this period.

20. A male patient must agree to use a contraceptive as detailed in Appendix 2 of this

protocol during the treatment period and for at least 180 days after the last dose of

study treatment and refrain from donating sperm during this period.

Cohorts 1b, 2a, 2c:

1. Ability to comprehend and willingness to provide written informed consent (ICF) for

the study.

2. Age ≥ 18 years.

3. Histologically or cytologically confirmed CRC and MSS/MMR proficient status confirmed

by polymerase chain reaction (PCR)/ immunohistochemistry or next generation sequencing

(NGS) assay at local institution.

4. Must have received a first line of SoC systemic therapy (physician choice) for stage

IV disease and completed the therapy. They must have an ongoing partial response (PR)

or a stable disease (SD) at the completion of this therapy, completion of therapy as

defined by the investigator, however, with a minimum number of 6 months.

Note: Patient may have also received prior adjuvant therapy for stage II or III

colorectal cancer, however the adjuvant treatment for stage II and III will not be

considered as a prior line of therapy in case of relapse more than 6 months after the

end of treatment.

5. Presence of at least 1 measurable lesion by computed tomography or magnetic resonance

imaging per RECIST v1.1 as determined by the local site investigator/radiologist

assessment.

6. Presence of at least one liver lesion amenable to repeated biopsy, ideally not the one

being used for measuring. If the investigator judges the biopsies to be a risk or an

undue inconvenience for the patient health/condition, they may be skipped (however, a

minimum of 50% of patients must undergo the paired biopsies).

7. Willingness to undergo two fresh liver biopsies (pre-treatment and on-treatment). If

the investigator judges the biopsies to be a risk or an undue inconvenience for the

patient health/condition, they may be skipped (however, a minimum of 50% of patients

must undergo the paired biopsies).

8. ECOG performance status 0 to 2 (see Appendix 1).

9. Life expectancy of at least 6 months.

10. Has resolution of all toxicities and any toxic effect(s) of the most recent prior

therapy to Grade 1 or less (except alopecia). Patients with ≤ Grade 2 neuropathy and

Grade ≤ 2 fatigue are an exception and may enroll.

11. Adequate renal, hepatic, thyroid and hematologic functions as defined by laboratory

parameters ≤ 7 days before study treatment initiation.

12. Absolute neutrophil count ≥ 1.5 × 109/L.

13. Absolute lymphocyte count ≥ 0.5 × 109/L.

14. Platelets ≥ 100 × 109/L.

15. Hemoglobin level ≥ 9 g/dL.

16. Measured or calculated creatinine clearance (glomerular filtration rate can also be

used in place of creatinine clearance) ≥ 50 mL/min according to the formula of

Cockcroft-Gault (see Appendix 6).

17. Total bilirubin ≤ 1.5 × ULN; if total bilirubin is > 1.5 x ULN then direct bilirubin

must be ≤ 1.5 × ULN. Patients with known Gilbert's Syndrome may enroll if total

bilirubin ≤ 3 × ULN.

18. ALT/AST ≤ 2.5 × ULN or ≤ 5 × ULN in patients with hepatic involvement.

19. A female patient is eligible to participate if she is not pregnant (see Appendix 2),

not breastfeeding, and at least one of the following conditions applies:

Not a woman of childbearing potential (WOCBP) as defined in Appendix 2. OR A WOCBP who

agrees to use highly effective contraceptive methods as outlined in Appendix 2 during

the treatment period and for at least 180 days after the last dose of study treatment

and refrain from egg donation during this period.

20. A male patient must agree to use a contraceptive as detailed in Appendix 2 of this

protocol during the treatment period and for at least 180 days after the last dose of

study treatment and refrain from donating sperm during this period.

Cohort 2b:

1. Ability to comprehend and willingness to provide written informed consent (ICF) for

the study.

2. Age ≥ 18 years.

3. Histologically or cytologically confirmed CRC and MSS/MMR proficient status confirmed

by PCR/immunohistochemistry or NGS assay at local institution.

4. Radiological evidence (CT/MRI) of liver-limited stage IV CRC.

5. Must have received first line neoadjuvant SoC systemic therapy (physician choice) for

stage IV disease. May have received up to 12 weeks of this systemic SoC therapy.

Note: Patient may have also received prior adjuvant therapy for stage II or III

colorectal cancer, however the adjuvant treatment for stage II and III will not be

considered as a prior line of therapy in case of relapse more than 6 months after the

end of treatment.

6. Absence of disease progression following neoadjuvant chemotherapy.

7. Eligible for en bloc surgery (resection of liver metastasis together with primary

tumor if still present) with curative intent.

8. ECOG performance status 0 to 2 (see Appendix 1).

9. Life expectancy of at least 12 months.

10. Adequate renal, hepatic, thyroid and hematologic functions as defined by laboratory

parameters ≤ 7 days before study treatment initiation.

11. Absolute neutrophil count ≥ 1.5 × 109 /L.

12. Absolute lymphocyte count ≥ 0.5 × 109 /L.

13. Platelets ≥ 100 × 109/L.

14. Hemoglobin level ≥ 9 g/dL.

15. Measured or calculated creatinine clearance (glomerular filtration rate can also be

used in place of creatinine clearance) ≥ 50 mL/min according to the formula of

Cockcroft-Gault (see Appendix 6).

16. Total bilirubin ≤ 1.5 × ULN; if total bilirubin is > 1.5 x ULN then direct bilirubin

must be ≤ 1.5 × ULN. Patients with known Gilbert's Syndrome may enroll if total

bilirubin ≤ 3 × ULN.

17. ALT/AST ≤ 2.5 × ULN or ≤ 5 × ULN in patients with hepatic involvement.

18. A female patient is eligible to participate if she is not pregnant (see Appendix 2),

not breastfeeding, and at least one of the following conditions applies:

Not a woman of childbearing potential (WOCBP) as defined in Appendix 2. OR A WOCBP who

agrees to use highly effective contraceptive methods as outlined in Appendix 2 during

the treatment period and for at least 180 days after the last dose of study treatment

and refrain from egg donation during this period.

19. A male patient must agree to use a contraceptive as detailed in Appendix 2 of this

protocol during the treatment period and for at least 180 days after the last dose of

study treatment and refrain from donating sperm during this period.

Exclusion Criteria:

All Cohorts:

1. Unwilling or unable to follow protocol requirements or to give informed consent.

2. Gastro-intestinal bowel obstruction (partial or complete).

3. Participation in any other study with an investigational study drug or device requires

Medical Monitor approval.

4. Prior monoclonal antibody within 4 weeks or 5 half-lives (whichever is shorter) before

administration of study treatment with the exception of bevacizumab (Avastin®) which

may have been received within 15 days from initiation of study treatment. Supportive

care (e.g. denosumab) may be used before and during study treatment.

5. Prior therapy with checkpoint inhibitors (anti-programmed death 1 (anti-PD-1),

anti-programmed death-ligand 1 (anti-PD-L1), anti-cytotoxic T-lymphocyte-associated

protein 4 (anti-CTLA-4)). Patients must not have received any investigational

immunotherapy neither.

6. Prior chemotherapy or targeted small molecule therapy within 15 days from initiation

of study treatment.

7. Prior radiotherapy within 2 weeks of enrolment or within 4 weeks of enrolment in the

case of radiation to central nervous system (CNS), which requires ≥ 4-week washout.

Patients must have recovered from all radiation-related toxicities, not require

corticosteroids, and not have had radiation pneumonitis.

8. Major (according the Investigator's judgment) surgery within 12 weeks before

enrolment.

9. Known additional malignancy that is progressing or requires active treatment, or

history of other malignancy within 2 years of study entry with the exception of cured

basal cell or squamous cell carcinoma of the skin, superficial bladder cancer,

prostate intraepithelial neoplasm, carcinoma in situ of the cervix, ductal or lobular

carcinoma in situ of the breast, or other non-invasive or indolent malignancy, or

cancers from which the patient has been disease-free for > 1 year, after treatment

with curative intent.

10. Immunosuppression including the continued use of systemic (at prednisone dose

equivalent of > 10 mg) or topical steroids at or near the injection site (excluding

inhaled and eye drop-containing corticosteroids) or the use of immunosuppressive

agents for any concurrent condition. All other corticosteroids must be discontinued >

4 weeks prior to first study treatment administration.

11. Previous vaccination (either therapeutic and/or prophylactic) against mCRC.

12. Pregnant/nursing women or unwilling to comply with acceptable contraceptive methods

during study course.

13. History of autoimmune disease including any active autoimmune disease except vitiligo

or childhood asthma.

14. Dermatological disease requiring local immunosuppressive agent.

15. Chronic or concurrent active infectious disease requiring systemic antibodies,

antifungal, or antiviral treatment.

16. Known medical history of human immunodeficiency virus (HIV) infection or known medical

history of acquired immunodeficiency syndrome (AIDS). HIV testing is not required

unless mandated by the local health authority.

17. Has known history of or is positive for hepatitis B (hepatitis B virus surface antigen

[HBsAg] reactive) or hepatitis C (HCV RNA).

Note: Testing must be performed to determine eligibility. - Hepatitis B virus DNA must

be undetectable and HBsAg negative at screening visit. - Hepatitis C antibody testing

is allowed for screening purposes in countries where HCV RNA is not part of standard

of care. In these cases, HCV antibody positive patients will be excluded. - Patients

who have had definitive treatment for HCV are permitted if HCV RNA is undetectable at

screening visit.

18. Known active CNS metastasis and/or carcinomatous meningitis.

19. Known cerebral oedema.

20. Live vaccine received within 30 days before initiation of study treatment. Examples of

live vaccines include, but are not limited to, the following: measles, mumps, rubella,

chicken pox, yellow fever, rabies, Bacillus Calmette-Guérin, and typhoid vaccine.

Seasonal influenza vaccines for injection are generally killed virus vaccines and are

allowed. however, intranasal influenza vaccines (FluMist®) are live attenuated

vaccines and are not allowed.

21. History of allergy or hypersensitivity to any of the study drugs or study drug

components.

22. Any condition in the judgment of the Investigator which makes the patient unsuitable

for trial participation.

Cohorts 1b, 2a, 2b, 2c:

23. Has received more than 1 line of therapy for stage IV disease (neoadjuvant therapy in

Cohort 2b counts as 1 line).

24. History of pneumonitis within the last 5 years.

25. Active interstitial lung disease (ILD)/pneumonitis or a history of ILD/pneumonitis

requiring treatment with systemic steroids and/or whose pulse oximetry is less than

92% "on room air".

26. Any of the following cardiac criteria:

- Mean resting corrected QT interval (QTc) > 470 msec.

- Any clinically important abnormalities (as assessed by the Investigator) in

rhythm, conduction, or morphology of resting ECGs, e.g., complete left bundle

branch block, third degree heart block.

- Any factors that increase the risk of QTc prolongation or risk of arrhythmic

events such as heart failure, hypokalemia, congenital long QT syndrome, family

history of long QT syndrome or unexplained sudden death under 40 years old, or

any concomitant medication known to prolong the QT interval (according to

institutional guidelines).

- Ejection fraction (EF) < 55% or the lower limit of normal of the institutional

standard will be excluded. Only in cases where the Investigator (or the treating

physician or both) suspects cardiac disease with negative effect on the EF will

the EF be measured during screening using an appropriate method according to

local standards to confirm eligibility (e.g. echocardiogram [ECHO], multi-gated

acquisition scan [MUGA]. A historic measurement of EF no older than 6 months

prior to first study treatment administration can be accepted provided that there

is clinical evidence that the EF value has not worsened since this measurement in

the opinion of the Investigator or the treating physician or both.

Studien-Rationale

Primary outcome:

1. Evaluate safety and tolerability by measure of incidence of treatment-emergent adverse events (AEs) and serious adverse events (SAEs) graded using the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 (Time Frame - 1 year):
Safety



Secondary outcome:

1. Evaluate anti-tumor effect of ATP128 alone or in combination with BI 754091 by measure of Overall Response Rate (ORR) (Time Frame - 1 year):
Based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1

2. Confirm recommended phase 2 dose (RP2D) of ATP128 in combination with BI 754091 (Time Frame - 1 year):
Based on evaluation of AEs with the support of pharmacodynamics

3. Evaluate anti-tumor effect of ATP128 alone or in combination with BI 754091 by measure of Best Overall Response (BOR) (Time Frame - 1 year):
Based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1

4. Evaluate anti-tumor effect of ATP128 alone or in combination with BI 754091 by measure of Duration of Response (DoR) (Time Frame - 1 year):
Based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1

5. Evaluate anti-tumor effect of ATP128 alone or in combination with BI 754091 by measure of Progression Free Survival (PFS) (Time Frame - 1 year):
Based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1

6. Evaluate anti-tumor effect of ATP128 alone or in combination with BI 754091 by measure of Relapse Free Survival (RFS) (Time Frame - 1 year):
Based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1

Studien-Arme

  • Experimental: Cohort 1a
    6 patients with stage IV CRC having failed SoC therapies
  • Experimental: Cohort 1b
    6 patients with stage IV MSS/MMRp CRC being in SD or PR after first line of SoC (6 months duration at minimum)
  • Experimental: Cohort 2a
    5 patients with stage IV MSS/MMRp CRC being in SD or PR after first line of SoC (6 months duration at minimum)
  • Experimental: Cohort 2b
    15 patients with stage IV MSS/MMRp hepatic-limited metastatic CRC

Geprüfte Regime

  • ATP128:
    6 injections of ATP128
  • BI 754091:
    ≥ 7 infusions of BI 754091

Quelle: ClinicalTrials.gov


Das könnte Sie auch interessieren
EHA 2021
  • SCD: Häufigere und längere VOC-bedingte Krankenhausaufenthalte nach Vorgeschichte von VOC-Hospitalisierungen – Ergebnisse einer Beobachtungsstudie
  • Real-World-Daten des ERNEST-Registers untermauern Überlebensvorteil unter Ruxolitinib bei primärer und sekundärer Myelofibrose
  • I-WISh-Studie: Ärzte sehen TPO-RAs als beste Option, um anhaltende Remissionen bei ITP-Patienten zu erzielen
  • Phase-III-Studie REACH2 bei steroidrefraktärer akuter GvHD: Hohes Ansprechen auf Ruxolitinib auch nach Crossover
  • SCD: Neues digitales Schmerztagebuch zur tagesaktuellen Erfassung von VOCs wird in Beobachtungsstudie geprüft
  • Französische Real-World-Studie: Eltrombopag meist frühzeitig nach ITP-Diagnose im Rahmen eines Off-label-Use eingesetzt
  • Fortgeschrittene systemische Mastozytose: Französische Real-World-Studie bestätigt klinische Studiendaten zur Wirksamkeit von Midostaurin
  • CML-Management weitgehend leitliniengerecht, aber verbesserungsfähig – Ergebnisse einer Querschnittsbefragung bei britischen Hämatologen
  • Britische Real-World-Studie: Kardiovaskuläres Risikomanagement bei MPN-Patienten in der Primärversorgung nicht optimal
  • Myelofibrose: Früher Einsatz von Ruxolitinib unabhängig vom Ausmaß der Knochenmarkfibrose