| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
Phase 1: Advanced solid tumors, metastatic pancreatic adenocarcinoma
Phase 2: Specified metastatic solid tumors |
|
| E.1.1.1 | Medical condition in easily understood language |
Phase 1: Advanced, abnormal mass of cancerous tissue and cancer of the pancreas that has spread to other parts of the body
Phase 2: cells that break away from original solid tumor and form new tumors |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
| MedDRA Classification |
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
The primary objective of the Dose Escalation phase of the study is to determine the MTD or RP2D of GB1275 monotherapy and GB1275 in combination with pembrolizumab or in combination with nab-paclitaxel and gemcitabine through evaluation of safety and PK.
The primary objective of the Basket phase of the study is to assess the efficacy of GB1275 in combination with SOC or pembrolizumab through determination of objective response rate (ORR) within each basket expansion cohort. |
|
| E.2.2 | Secondary objectives of the trial |
The secondary objectives of the Dose Escalation phase:
1) To further assess the efficacy and evaluate the safety and tolerability of GB1275 in combination with SOC (nab-paclitaxel and gemcitabine) as the first line therapy in subjects with newly diagnosed metastatic pancreatic adenocarcinoma
2) To assess the PK of GB1275 in subjects with newly diagnosed metastatic pancreatic adenocarcinoma
The secondary objectives of the Basket phase:
1) To further assess the efficacy and evaluate the safety and tolerability of GB1275 in combination with pembrolizumab in subjects with MSS metastatic colorectal adenocarcinoma or recurrent/metastatic gastric/GEJ adenocarcinoma with PD-L1 expression
2) To assess the PK of GB1275 in subjects with MSS metastatic colorectal adenocarcinoma or recurrent/metastatic gastric/GEJ adenocarcinoma with PD-L1 expression
|
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Subjects at least 18 years of age at the time of signing the informed consent form (ICF) prior to initiation of any study specific activities/procedures.
2. For Regimen A and Regimen B: subjects with histologically or cytologically confirmed diagnosis of locally advanced or metastatic pancreatic adenocarcinoma, or esophageal adenocarcinoma, or esophageal squamous cell carcinoma, or gastric/gastroesophageal junction adenocarcinoma, or TNBC, or metastatic castrate resistant prostate cancer, or MSS colorectal adenocarcinoma.
Notes: for colorectal adenocarcinoma subject, a documented MSS tumor determined by CLIA-approved local laboratory is required for enrollment.
3. For Regimen C: the subject must have histologically and/or cytologically confirmed adenocarcinoma of the pancreas and has a diagnosis of stage IV adenocarcinoma of the pancreas (American Joint Committee on Cancer [AJCC] stage IV).
4. Subjects who have exhausted potential curative options and who are relapsed or refractory to, or intolerant of, or refuse one or more of the approved or standard of care established therapy known to provide clinical benefit for their condition.
Note: there is no limit to the number of prior treatment regimens.
5. Subject must have a site of disease that is amenable to biopsy, and be a candidate for tumor biopsy prior to the first dose of the study drug to be considered for the study. Exceptions may be granted after documented discussion with the sponsor. For subjects whose baseline tumor tissues do not contain tumor cells, submission of Formalin-fixed, paraffin embedded (FFPE) or slides (minimum of 15) from archival tissues that were collected within one year prior to the first dose of the study (if available) may be requested.
6. Subject has a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale.
7. Demonstrate adequate organ function as defined below. All screening laboratories for organ functions should be performed within 14 days of initiating the study drug(s).
8. Male or female. Contraception use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
9. Women of childbearing potential must have negative serum pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin [HCG]) within 14 days prior to receiving the first administration of the study drug(s) and a negative urine pregnancy test on Cycle 1 Day 1 before first administration of the study drug if screening serum pregnancy test was done more than 3 days prior to the first administration of the study drug(s). If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test is required.
10. Women of non-childbearing potential: Evidence of post-menopausal status. Refer to Appendix 4 (Section 10.4) for definitions.
11. Women of childbearing potential who are not abstinent and intend to be sexually active with a nonsterilized male partner must be willing to use an adequate method of contraception. Refer to Appendix 4 (Section 10.4) for contraception guidance.
12. Male subjects: Non-sterilized male subjects who are not abstinent and intend to be sexually active with a female partner of childbearing potential must use male condoms as described in Appendix 4 (Section 10.4).
13. The subject (or legally acceptable representative if applicable) provides written informed consent for the study which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.
14. For subjects enrolled into Phase 1 Expansion with Regimen B or Dose escalation Phase with Regimen C, the subject has 1 or more tumors measurable per RECIST v1.1 as assessed by the local site Investigator/radiology besides the ones that would be biopsied. Subjects with CRPC who have measurable PSA and bony disease only to be enrolled into Phase 1 Expansion with Regimen B.
15. For subjects enrolled in Phase 1 Dose Escalation for Regimen A & B or Phase 1 Expansion with Regimen B: Subjects with tumor types that have CPI approved for the indication must have developed disease progression after receiving initial treatment benefit .This includes subjects with gastric/GEJ cancer, esophageal cancer and TNBC in addition to NSCLC, SCLC, HNSCC, RCC, UC, and HCC, etc.. Note: melanoma patients not to be enrolled into Phase 1 Expansion
16. Subjects with gastric/GEJ cancer, esophageal cancer, TNBC, locally advanced or metastatic PDAC, MSS CRC, and CRPC who have either received prior CPI or have never received CPI. |
|
| E.4 | Principal exclusion criteria |
1. Has a history of another malignancy within 2 years prior to first study drug(s) administration, unless the malignancy was treated with curative intent and the likelihood of relapse is <5% in 2 years.
2. Has untreated or symptomatic central nervous system (CNS) metastases and/or carcinomatous meningitis.
3. Any unresolved Grade 2 or greater reversible toxicity from previous anticancer therapy except alopecia or Grade 2 neuropathy.
4. Clinically significant cardiovascular disease.
5. Has an active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy within 14 days of Cycle 1 Day 1.
6. Pregnant or nursing.
7. Known history of testing positive for human immunodeficiency virus (HIV), and/or positive test for Hepatitis B virus surface antigen (HBsAg) or a and/or positive Hep C antibody result with detectable hepatitis C virus (HCV) ribonucleic acid (RNA) indicating acute or chronic infection.
8. A serious nonmalignant disease (eg, psychiatric, substance abuse, uncontrolled intercurrent illness, etc.) that could compromise protocol objectives in the opinion of the Investigator and/or the Sponsor.
9. Any other condition that, in the opinion of the Investigator, would prohibit the subject from participating in the study.
10. Gastrointestinal (GI) tract disease causing the inability to take oral medication.
11. Malabsorption syndrome.
12. Has active autoimmune disease requiring systemic therapy in the last 2 years prior to the first dose of study drug(s) (i.e., with use of disease modifying agents, systemic corticosteroids or immunosuppressive drugs).
Note: Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed.
13. A history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
14. Undergone major surgery within 4 weeks and have wound(s) not healing completely prior to Cycle 1, Day 1.
15. Received prior systemic anticancer therapies within 4 weeks of biologics and 2 weeks of chemotherapy or targeted small molecule therapy or herb supplements that are used for the treatment of the malignancy under the study (6 weeks for nitrosoureas or Mitomycin C) prior to study treatment.
Note: Prior systemic anticancer therapy is not allowed for subjects to be enrolled into Pancreatic Adenocarcinoma Expansion Cohort 1.
16. Has received prior radiotherapy within 2 weeks of start of study treatment. Subjects 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.
17. Previously received treatment with a myeloid targeting agent for example a CSF1R inhibitor or a CCR2/5 inhibitor.
18. Use of medications that are known to definitely prolong the QT interval and/or are associated with a risk of Torsades de Pointes (TdP) within 14 days of Cycle 1 Day 1
19. Use of amiodarone within 90 days prior to Cycle 1 Day 1.
20. Received a live vaccine within 30 days prior to the first dose of study drug(s). 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 (eg, FluMist®) are live attenuated vaccines and are not allowed.
21. Received OATP 1B1/1B3 substrates such as pitavastatin, simvastatin, fexofenadine, and bosentan within 14 days of Cycle 1 Day 1.
22. Received inhibitors and inducers of CYP3A and CYP2C8 inhibitors (eg, gemfibrozil, clopidogrel, teriflunomide, deferasirox, telithromycin, trimethoprim) or inducers (eg rifampin) within 14 days of Cycle 1 Day 1.
23. Prior history of inability to tolerate anti-PD-1, anti-PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX 40, CD137).
24. Has had an allogeneic tissue/solid organ transplant.
25. Immunosuppressive doses of systemic medications, such as steroids (doses > 10 mg/day prednisone or equivalent daily) within 2 weeks before study drug(s) administration for active autoimmune disease.
26. Currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study drug(s).
27. Subjects in Phase 1 Expansion with Regimen B only with tumor types that have CPI approved for the indication who have never received CPI or have not had treatment benefit from the last single agent CPI that is approved for the indication or in combination with standard of care therapy
Exception: gastric/GEJ, esophageal cancer and TNBC may enter if never received CPI. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Escalation (Regimen A and B) and Phase 1 Expansion Regimen B:
• Incidence of DLTs, AEs, and SAEs overall, by severity, by relationship to each study drug, and those that led to discontinuation of study drug(s)
• Number and frequency of clinically significant laboratory, electrocardiogram, and vital sign abnormalities
• Plasma concentrations and PK parameters of GB1275 and metabolites as appropriate
Escalation (Regimen C):
• Incidence of DLTs, AEs, and SAEs overall, by severity, by relationship to each study drug, and those that led to discontinuation of study drug(s)
• Number and frequency of clinically significant laboratory, electrocardiogram, and vital sign abnormalities
Basket (Cohort 1):
• Objective response rate (ORR) defined as the proportion of subjects with best overall confirmed response (BOCR) of either a complete response (CR) or partial response (PR) as assessed by the Investigator based on response evaluation criteria in solid tumors (RECIST) v1.1
Expansion (Cohort 2):
• ORR defined as the proportion of subjects with BOCR of either a CR or PR as assessed by the Investigator based on RECIST v1.1
Basket (Cohort 3)
• ORR defined as the proportion of subjects with BOCR of either a CR or PR as assessed by the Investigator in the Efficacy Evaluable Population
|
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
Data/samples collected at screening, day 1,2,8 and 15 of Cycle 1 and day one of every other cycle.
SAE collection will start after the consent.
ECG will be collected predose and postdose (2 and/or 6 h) |
|
| E.5.2 | Secondary end point(s) |
Escalation (Regimen C):
• Plasma concentrations and PK parameters of GB1275 and metabolites as appropriate
• Plasma concentrations and PK parameters of gemcitabine (and metabolite
difluorodeoxyuridine) and nab-paclitaxel (total and free) with and without GB1275
Basket:
•DOR
• TTR
• CBR
• PFS
• TTP
• OS
• Incidence of AEs, and SAEs overall, by severity, by relationship to each study drug, and those that led to discontinuation of study drug(s)
• Number and frequency of clinically significant laboratory, electrocardiogram, and vital sign abnormalities
• Plasma concentrations of GB1275 and metabolites as appropriate |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
Data/samples collected at screening, day 1,2,8 and 15 of Cycle 1 and day one of every other cycle.
SAE collection will start after the consent.
ECG will be collected predose and postdose (2 and/or 6 h) |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | Yes |
| E.7.1.1 | First administration to humans | Yes |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | No |
| E.8.1.1 | Randomised | No |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
| E.8.4 | The trial involves multiple sites in the Member State concerned | No |
| E.8.5 | The trial involves multiple Member States | No |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| United Kingdom |
| United States |
|
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 2 |
| E.8.9.1 | In the Member State concerned months | 0 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 2 |
| E.8.9.2 | In all countries concerned by the trial months | 0 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
Print
