Phase 1/2 Study of ABI-009 in Nonmuscle Invasive Bladder Cancer

• Sponsor: Aadi Bioscience, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02009332
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 21
• Locations: 2
• Arms: 6
• Actual Duration (Months): 67.7
• Patients Per Site: 10.5
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

Purpose of this study is to determine appropriate dosing of ABI-009 and evaluate the safety and anti-tumor activity of ABI-009 in treatment of non-muscle invasive bladder cancer

Condition or Disease	Intervention/Treatment	Phase
Non-muscle Invasive Bladder Cancer (NMIBC)	Drug: ABI-009; Drug: Gemcitabine	Phase 1/Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 21 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Intervention Model Description: The phase 1 dose-escalation portion used the 3+3 dose escalation rule. Initially 3 patients will be treated. If none develops DLT following the third weekly instillation, the dose can be escalated. If only 1 of the first 3 patients develops DLT, then an additional 3 patients will be treated at that dose. At any dose level, if 2 or more cases develop DLT, the prior dose will be defined as the MDD once 6 patients have been treated at this level with less than 2 patients experiencing a DLT. In phase 2, up to 29 patients will receive intravesical ABI-009 and gemcitabine using the Simon 2-stage design: initially, there will be only 10 patients enrolled with a rejection rule that only if there are 2 or more positive responses will the study proceed to further enrollment of the next 19 patients.The phase 1 dose-escalation portion used the 3+3 dose escalation rule. Initially 3 patients will be treated. If none develops DLT following the third weekly instillation, the dose can be escalated. If only 1 of the first 3 patients develops DLT, then an additional 3 patients will be treated at that dose. At any dose level, if 2 or more cases develop DLT, the prior dose will be defined as the MDD once 6 patients have been treated at this level with less than 2 patients experiencing a DLT. In phase 2, up to 29 patients will receive intravesical ABI-009 and gemcitabine using the Simon 2-stage design: initially, there will be only 10 patients enrolled with a rejection rule that only if there are 2 or more positive responses will the study proceed to further enrollment of the next 19 patients.
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Combined Phase 1 and Phase 2 Study of Albumin-bound Rapamycin Nanoparticles (Nab-rapamycin, ABI-009) in the Treatment of BCG Refractory or Recurrent Nonmuscle Invasive Transitional Cell Bladder Cancer
• Actual Study Start Date: Apr 9, 2014
• Actual Primary Completion Date: Dec 1, 2019
• Actual Study Completion Date: Dec 1, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Phase 1: ABI-009 100 mg/week Phase 1, Cohort 1: ABI-009 injectable suspension, 100 mg in 80 mL 0.9% saline, administered intravesically and retained for 2 hours, once per week for 6 weeks	Drug: ABI-009; ABI-009 is a nanoparticle albumin-bound (nab®) formulation of the mammalian Target of Rapamycin ( mTOR) inhibitor, sirolimus. Specifically, ABI-009 is a sterile lyophilized powder of albumin-bound sirolimus nanoparticles with a mean particle size of less than 100 nm.; Other Names: nab-sirolimus nab-rapamycin
Experimental: Phase 1: ABI-009 200 mg/week Phase 1, Cohort 2: ABI-009 injectable suspension, 200 mg in 80 mL 0.9% saline, administered intravesically and retained for 2 hours, once per week for 6 weeks	Drug: ABI-009; ABI-009 is a nanoparticle albumin-bound (nab®) formulation of the mammalian Target of Rapamycin ( mTOR) inhibitor, sirolimus. Specifically, ABI-009 is a sterile lyophilized powder of albumin-bound sirolimus nanoparticles with a mean particle size of less than 100 nm.; Other Names: nab-sirolimus nab-rapamycin
Experimental: Phase 1: ABI-009 100 mg 2×/week Phase 1, Cohort 2b: ABI-009 injectable suspension, 100 mg in 80 mL 0.9% saline, administered intravesically and retained for 2 hours, twice per week (total dose 200 mg per week) for 6 weeks	Drug: ABI-009; ABI-009 is a nanoparticle albumin-bound (nab®) formulation of the mammalian Target of Rapamycin ( mTOR) inhibitor, sirolimus. Specifically, ABI-009 is a sterile lyophilized powder of albumin-bound sirolimus nanoparticles with a mean particle size of less than 100 nm.; Other Names: nab-sirolimus nab-rapamycin
Experimental: Phase 1: ABI-009 300 mg/week Phase 1, Cohort 3: ABI-009 injectable suspension, 300 mg in 80 mL 0.9% saline, administered intravesically and retained for 2 hours, once per week for 6 weeks	Drug: ABI-009; ABI-009 is a nanoparticle albumin-bound (nab®) formulation of the mammalian Target of Rapamycin ( mTOR) inhibitor, sirolimus. Specifically, ABI-009 is a sterile lyophilized powder of albumin-bound sirolimus nanoparticles with a mean particle size of less than 100 nm.; Other Names: nab-sirolimus nab-rapamycin
Experimental: Phase 1: ABI-009 400 mg/week Phase 1, Cohort 4: ABI-009 injectable suspension, 400 mg in 80 mL 0.9% saline, administered intravesically and retained for 2 hours, once per week for 6 weeks	Drug: ABI-009; ABI-009 is a nanoparticle albumin-bound (nab®) formulation of the mammalian Target of Rapamycin ( mTOR) inhibitor, sirolimus. Specifically, ABI-009 is a sterile lyophilized powder of albumin-bound sirolimus nanoparticles with a mean particle size of less than 100 nm.; Other Names: nab-sirolimus nab-rapamycin
Experimental: Phase 2: ABI-009 400 mg/week + Gemcitabine 2000 mg/week ABI-009 injectable suspension, 200 mg in 80 mL 0.9% saline, administered intravesically and retained for 1 hour, once per week for 6 weeks; Gemcitabine, 2000 mg in 100 mL saline, administered intravesically after voiding of ABI-009 and retained for 1 hour, once per week for 6 weeks	Drug: ABI-009; ABI-009 is a nanoparticle albumin-bound (nab®) formulation of the mammalian Target of Rapamycin ( mTOR) inhibitor, sirolimus. Specifically, ABI-009 is a sterile lyophilized powder of albumin-bound sirolimus nanoparticles with a mean particle size of less than 100 nm.; Other Names: nab-sirolimus nab-rapamycin ; Drug: Gemcitabine; Gemcitabine is administered after ABI-009 in the Phase 2 study.

Outcome Measures

Primary Outcome Measures

1. Phase 1: Dose Limiting Toxicities (DLT) Following Intravesical Administration of ABI-009 [Duration of treatment (6 weeks) plus 30 days follow up (up to 2.5 months)]

   The primary endpoint of the Phase 1 study is DLT following intravesical administration of ABI-009 in patients with BCG refractory or recurrent nonmuscle-invasive transitional cell carcinoma (TCC) of the bladder to identify maximum deliverable dose (MDD). Systemic DLT will be defined as any grade systemic toxicity using the NCI CTCAE version 4.0. Local dose limiting toxicity was defined as grade 3 or 4 bladder toxicity (hematuria, dysuria, urinary retention, urinary frequency/urgency, or bladder spasms) using the NCI CTCAE version 4.0.

2. Phase 2: Number of Participants Achieving a Complete Response Following Intravesical Administration of ABI-009 and Gemcitabine [End of Study [EOS, 3 months]]

   The primary objective of the Phase 2 study is to evaluate the utility (potential for clinical efficacy) of ABI-009 in combination with gemcitabine in the treatment of BCG refractory or recurrent nonmuscle-invasive TCC of the bladder. Response rate will be measured and documented at the 6-week post-treatment assessment, including cystoscopy with biopsy. A complete response is defined as a cancer-negative biopsy at the 6-week post-treatment cystoscopy. No response will be defined as positive cystoscopic biopsy.

Secondary Outcome Measures

1. Phase 1: Number of Participants Achieving a Complete Response Following Intravesical Administration of ABI-009 [End of Study [EOS, 3 months]]

   Response rate will be measured and documented at the 6-week post-treatment assessment, including cystoscopy with biopsy. A complete response is defined as a cancer-negative biopsy at the 6-week post-treatment cystoscopy. No response will be defined as positive cystoscopic biopsy.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Patients must have a diagnosis of transitional cell carcinoma (TCC) of the urinary bladder confirmed at the study institution. The patient must have demonstrated nonmuscle-invasive bladder cancer refractory or recurrent to standard intravesical therapy. Refractory disease is defined as failure to achieve tumor-free status by 6 months of initiation of adequate BCG therapy. Recurrent disease is defined as reappearance of disease after achieving a tumor-free status by 6 months of initiation of adequate BCG therapy. Adequate BCG therapy includes at least 6 weeks induction plus 3 additional doses of either induction or maintenance. Patients with a history of other intravesical agents (except nab-rapamycin or gemcitabine) in addition to standard BCG will also be allowed to enroll. All grossly visible disease must be fully resected and pathologic stage will be confirmed at the institution where the patient is enrolled. This will include stage Ta, T1, Tis and exclude all patients with muscle invasion (T2).

2. For phase 1, patients with multifocal low-grade Ta histology will be eligible for participation

3. For phase 2, individuals with Ta disease only must have documentation of high-grade histology

4. For phase 2, prior intravesical treatment with nab-rapamycin or gemcitabine is not allowed

5. Age >18 and must be able to read, understand, and sign informed consent

6. Performance Status: ECOG 0, 1, and 2 (See Appendix III)

7. Hematologic inclusion within 2 weeks of start of treatment

8. Absolute neutrophil count >1,500/mm3

9. Hemoglobin >9.0 g/dl

10. Platelet count >100,000/mm3

11. Hepatic inclusion within 2 weeks of entry

12. Total bilirubin must be within normal limits.

13. Adequate renal function with serum creatinine ≤2.5 mg/dL

14. Aspartate transaminase (AST) and alanine transaminase (ALT) ≤2.5 x ULN for the institution, alkaline phosphatase ≤ 2.5 x ULN for the institution, unless bone metastasis is present in the absence of liver metastasis

15. Women of childbearing potential must have a negative pregnancy test.

16. All patients of childbearing potential must be willing to consent to using effective contraception, ie, intrauterine device, birth control pills, depo-provera, and condoms while on treatment and for 3 months after their participation in the study ends.

Exclusion Criteria:

1. Any other malignancy diagnosed within 1 year of study entry (except basal or squamous cell skin cancers or noninvasive cancer of the cervix) is excluded

2. Concurrent treatment with any chemotherapeutic agent

3. Women who are pregnant or lactating

4. History of vesicoureteral reflux or an indwelling urinary stent

5. Participation in any other research protocol involving administration of an investigational agent within 1 month prior to study entry

6. History of radiation to the pelvis

7. History of interstitial lung disease and/or pneumonitis

8. Evidence of metastatic disease

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Columbia University Medical Center	New York	New York	United States	10032
2	Vanderbilt University Medical Center	Nashville	Tennessee	United States	37232

Sponsors and Collaborators

• Aadi Bioscience, Inc.
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: James McKiernan, MD, Columbia University

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Apr 20, 2016

More Information

Publications

None provided.

• Responsible Party: Aadi Bioscience, Inc.
• ClinicalTrials.gov Identifier: NCT02009332
• Other Study ID Numbers: BC001; 1R42CA171552-01
• First Posted: Dec 12, 2013
• Last Update Posted: Jun 8, 2021
• Last Verified: May 1, 2021

• Additional relevant MeSH terms: Urinary Bladder Neoplasms; Gemcitabine; Sirolimus

Study Results

Participant Flow

Arm/Group Title	Phase 1: ABI-009 100 mg/Week	Phase 1: ABI-009 200 mg/Week	Phase 1: ABI-009 100 mg 2×/Week	Phase 1: ABI-009 300 mg/Week	Phase 1: ABI-009 400 mg/Week	Phase 2: ABI-009 200 mg/Week + Gemcitabine 2000 mg/Week
Arm/Group Description	Phase 1, Cohort 1: ABI-009 injectable suspension, 100 mg in 80 mL 0.9% saline, administered intravesically and retained for 2 hours, once per week for 6 weeks	Phase 1, Cohort 2: ABI-009 injectable suspension, 200 mg in 80 mL 0.9% saline, administered intravesically and retained for 2 hours, once per week for 6 weeks	Phase 1, Cohort 2b: ABI-009 injectable suspension, 100 mg in 80 mL 0.9% saline, administered intravesically and retained for 2 hours, twice per week (total dose 200 mg per week) for 6 weeks	Phase 1, Cohort 3: ABI-009 injectable suspension, 300 mg in 80 mL 0.9% saline, administered intravesically and retained for 2 hours, once per week for 6 weeks	Phase 1, Cohort 4: ABI-009 injectable suspension, 400 mg in 80 mL 0.9% saline, administered intravesically and retained for 2 hours, once per week for 6 weeks	ABI-009 injectable suspension, 200 mg in 80 mL 0.9% saline, administered intravesically and retained for 1 hour, once per week for 6 weeks; Gemcitabine, 2000 mg in 100 mL saline, administered intravesically after voiding of ABI-009 and retained for 1 hour, once per week for 6 weeks
Period Title: Phase 1: Dose Level 1 (Weeks 1-10)
STARTED	3	0	0	0	0	0
COMPLETED	3	0	0	0	0	0
NOT COMPLETED	0	0	0	0	0	0
Period Title: Phase 1: Dose Level 1 (Weeks 1-10)
STARTED	0	4	1	0	0	0
COMPLETED	0	3	1	0	0	0
NOT COMPLETED	0	1	0	0	0	0
Period Title: Phase 1: Dose Level 1 (Weeks 1-10)
STARTED	0	0	0	3	0	0
COMPLETED	0	0	0	3	0	0
NOT COMPLETED	0	0	0	0	0	0
Period Title: Phase 1: Dose Level 1 (Weeks 1-10)
STARTED	0	0	0	0	4	0
COMPLETED	0	0	0	0	3	0
NOT COMPLETED	0	0	0	0	1	0
Period Title: Phase 1: Dose Level 1 (Weeks 1-10)
STARTED	0	0	0	0	0	6
COMPLETED	0	0	0	0	0	5
NOT COMPLETED	0	0	0	0	0	1

Baseline Characteristics

Arm/Group Title	Phase 1: ABI-009 100 mg/Week	Phase 1: ABI-009 200 mg/Week	Phase 1: ABI-009 100 mg 2x/Week	Phase 1: ABI-009 300 mg/Week	Phase 1: ABI-009 400 mg/Week	Phase 2, Efficacy	Total
Arm/Group Description	Phase 1, Cohort 1: ABI-009 injectable suspension, 100 mg in 80 mL 0.9% saline, administered intravesically and retained for 2 hours, once per week for 6 weeks	Phase 1, Cohort 2: ABI-009 injectable suspension, 200 mg in 80 mL 0.9% saline, administered intravesically and retained for 2 hours, once per week for 6 weeks	Phase 1, Cohort 2b: ABI-009 injectable suspension, 100 mg in 80 mL 0.9% saline, administered intravesically and retained for 2 hours, twice per week (total dose 200 mg per week) for 6 weeks	Phase 1, Cohort 3: ABI-009 injectable suspension, 300 mg in 80 mL 0.9% saline, administered intravesically and retained for 2 hours, once per week for 6 weeks	Phase 1, Cohort 4: ABI-009 injectable suspension, 400 mg in 80 mL 0.9% saline, administered intravesically and retained for 2 hours, once per week for 6 weeks	ABI-009 injectable suspension, 200 mg in 80 mL 0.9% saline, administered intravesically and retained for 1 hour, once per week for 6 weeks; Gemcitabine, 2000 mg in 100 mL saline, administered intravesically after voiding of ABI-009 and retained for 1 hour, once per week for 6 weeks	Total of all reporting groups
Overall Participants	3	4	1	3	4	6	21
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	0 0%	3 75%	0 0%	0 0%	0 0%	0 0%	3 14.3%
>=65 years	3 100%	1 25%	1 100%	3 100%	4 100%	6 100%	18 85.7%
Sex: Female, Male (Count of Participants)
Female	1 33.3%	0 0%	0 0%	0 0%	0 0%	1 16.7%	2 9.5%
Male	2 66.7%	4 100%	1 100%	3 100%	4 100%	5 83.3%	19 90.5%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
White	3 100%	4 100%	1 100%	3 100%	4 100%	6 100%	21 100%
More than one race	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	3 100%	4 100%	1 100%	3 100%	4 100%	6 100%	21 100%

Outcome Measures

1. Primary Outcome

Title	Phase 1: Dose Limiting Toxicities (DLT) Following Intravesical Administration of ABI-009
Description	The primary endpoint of the Phase 1 study is DLT following intravesical administration of ABI-009 in patients with BCG refractory or recurrent nonmuscle-invasive transitional cell carcinoma (TCC) of the bladder to identify maximum deliverable dose (MDD). Systemic DLT will be defined as any grade systemic toxicity using the NCI CTCAE version 4.0. Local dose limiting toxicity was defined as grade 3 or 4 bladder toxicity (hematuria, dysuria, urinary retention, urinary frequency/urgency, or bladder spasms) using the NCI CTCAE version 4.0.
Time Frame	Duration of treatment (6 weeks) plus 30 days follow up (up to 2.5 months)

Outcome Measure Data

Analysis Population Description

All Phase 1 patients who received at least 1 treatment.

Arm/Group Title	Phase 1: ABI-009 100 mg/Week	Phase 1: ABI-009 200 mg/Week	Phase 1: ABI-009 100 mg 2×/Week	Phase 1: ABI-009 300 mg/Week	Phase 1: ABI-009 400 mg/Week
Arm/Group Description	Phase 1, Cohort 1: ABI-009 injectable suspension, 100 mg in 80 mL 0.9% saline, administered intravesically and retained for 2 hours, once per week for 6 weeks ABI-009: ABI-009 is a nanoparticle albumin-bound (nab®) formulation of the mammalian Target of Rapamycin ( mTOR) inhibitor, sirolimus. Specifically, ABI-009 is a sterile lyophilized powder of albumin-bound sirolimus nanoparticles with a mean particle size of less than 100 nm.	Phase 1, Cohort 2: ABI-009 injectable suspension, 200 mg in 80 mL 0.9% saline, administered intravesically and retained for 2 hours, once per week for 6 weeks ABI-009: ABI-009 is a nanoparticle albumin-bound (nab®) formulation of the mammalian Target of Rapamycin ( mTOR) inhibitor, sirolimus. Specifically, ABI-009 is a sterile lyophilized powder of albumin-bound sirolimus nanoparticles with a mean particle size of less than 100 nm.	Phase 1, Cohort 2b: ABI-009 injectable suspension, 100 mg in 80 mL 0.9% saline, administered intravesically and retained for 2 hours, twice per week (total dose 200 mg per week) for 6 weeks ABI-009: ABI-009 is a nanoparticle albumin-bound (nab®) formulation of the mammalian Target of Rapamycin ( mTOR) inhibitor, sirolimus. Specifically, ABI-009 is a sterile lyophilized powder of albumin-bound sirolimus nanoparticles with a mean particle size of less than 100 nm.	Phase 1, Cohort 3: ABI-009 injectable suspension, 300 mg in 80 mL 0.9% saline, administered intravesically and retained for 2 hours, once per week for 6 weeks ABI-009: ABI-009 is a nanoparticle albumin-bound (nab®) formulation of the mammalian Target of Rapamycin ( mTOR) inhibitor, sirolimus. Specifically, ABI-009 is a sterile lyophilized powder of albumin-bound sirolimus nanoparticles with a mean particle size of less than 100 nm.	Phase 1, Cohort 4: ABI-009 injectable suspension, 400 mg in 80 mL 0.9% saline, administered intravesically and retained for 2 hours, once per week for 6 weeks ABI-009: ABI-009 is a nanoparticle albumin-bound (nab®) formulation of the mammalian Target of Rapamycin ( mTOR) inhibitor, sirolimus. Specifically, ABI-009 is a sterile lyophilized powder of albumin-bound sirolimus nanoparticles with a mean particle size of less than 100 nm.
Measure Participants	3	4	1	3	4
Count of Participants [Participants]	0 0%	0 0%	0 0%	0 0%	0 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Phase 1: ABI-009 100 mg/Week, Phase 1: ABI-009 200 mg/Week, Phase 1: ABI-009 100 mg 2×/Week, Phase 1: ABI-009 300 mg/Week, Phase 1: ABI-009 400 mg/Week
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	maximum deliverable dose (MDD)
	Estimated Value	400
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	Maximum deliverable dose (MDD) was not reached in the Phase 1 study as no DLTs were observed in any of the dose groups up to ABI-009 400 mg/week.

2. Primary Outcome

Title	Phase 2: Number of Participants Achieving a Complete Response Following Intravesical Administration of ABI-009 and Gemcitabine
Description	The primary objective of the Phase 2 study is to evaluate the utility (potential for clinical efficacy) of ABI-009 in combination with gemcitabine in the treatment of BCG refractory or recurrent nonmuscle-invasive TCC of the bladder. Response rate will be measured and documented at the 6-week post-treatment assessment, including cystoscopy with biopsy. A complete response is defined as a cancer-negative biopsy at the 6-week post-treatment cystoscopy. No response will be defined as positive cystoscopic biopsy.
Time Frame	End of Study [EOS, 3 months]

Outcome Measure Data

Analysis Population Description

Analysis population includes all patients who have completed the planned 6 treatment cycles and have 6 week follow up cystoscopy data available

Arm/Group Title	Phase 2: ABI-009 400 mg/Week + Gemcitabine 2000 mg/Week
Arm/Group Description	ABI-009 injectable suspension, 200 mg in 80 mL 0.9% saline, administered intravesically and retained for 1 hour, once per week for 6 weeks; Gemcitabine, 2000 mg in 100 mL saline, administered intravesically after voiding of ABI-009 and retained for 1 hour, once per week for 6 weeks
Measure Participants	5
Count of Participants [Participants]	1 33.3%

3. Secondary Outcome

Title	Phase 1: Number of Participants Achieving a Complete Response Following Intravesical Administration of ABI-009
Description	Response rate will be measured and documented at the 6-week post-treatment assessment, including cystoscopy with biopsy. A complete response is defined as a cancer-negative biopsy at the 6-week post-treatment cystoscopy. No response will be defined as positive cystoscopic biopsy.
Time Frame	End of Study [EOS, 3 months]

Outcome Measure Data

Analysis Population Description

Analysis population includes all patients who have completed the planned 6 treatment cycles and have 6 week follow up cystoscopy data available.

Arm/Group Title	Phase 1: ABI-009 100 mg/Week	Phase 1: ABI-009 200 mg/Week	Phase 1: ABI-009 100 mg 2×/Week	Phase 1: ABI-009 300 mg/Week	Phase 1: ABI-009 400 mg/Week
Arm/Group Description	Phase 1, Cohort 1: ABI-009 injectable suspension, 100 mg in 80 mL 0.9% saline, administered intravesically and retained for 2 hours, once per week for 6 weeks ABI-009: ABI-009 is a nanoparticle albumin-bound (nab®) formulation of the mammalian Target of Rapamycin ( mTOR) inhibitor, sirolimus. Specifically, ABI-009 is a sterile lyophilized powder of albumin-bound sirolimus nanoparticles with a mean particle size of less than 100 nm.	Phase 1, Cohort 2: ABI-009 injectable suspension, 200 mg in 80 mL 0.9% saline, administered intravesically and retained for 2 hours, once per week for 6 weeks ABI-009: ABI-009 is a nanoparticle albumin-bound (nab®) formulation of the mammalian Target of Rapamycin ( mTOR) inhibitor, sirolimus. Specifically, ABI-009 is a sterile lyophilized powder of albumin-bound sirolimus nanoparticles with a mean particle size of less than 100 nm.	Phase 1, Cohort 2b: ABI-009 injectable suspension, 100 mg in 80 mL 0.9% saline, administered intravesically and retained for 2 hours, twice per week (total dose 200 mg per week) for 6 weeks ABI-009: ABI-009 is a nanoparticle albumin-bound (nab®) formulation of the mammalian Target of Rapamycin ( mTOR) inhibitor, sirolimus. Specifically, ABI-009 is a sterile lyophilized powder of albumin-bound sirolimus nanoparticles with a mean particle size of less than 100 nm.	Phase 1, Cohort 3: ABI-009 injectable suspension, 300 mg in 80 mL 0.9% saline, administered intravesically and retained for 2 hours, once per week for 6 weeks ABI-009: ABI-009 is a nanoparticle albumin-bound (nab®) formulation of the mammalian Target of Rapamycin ( mTOR) inhibitor, sirolimus. Specifically, ABI-009 is a sterile lyophilized powder of albumin-bound sirolimus nanoparticles with a mean particle size of less than 100 nm.	Phase 1, Cohort 4: ABI-009 injectable suspension, 400 mg in 80 mL 0.9% saline, administered intravesically and retained for 2 hours, once per week for 6 weeks ABI-009: ABI-009 is a nanoparticle albumin-bound (nab®) formulation of the mammalian Target of Rapamycin ( mTOR) inhibitor, sirolimus. Specifically, ABI-009 is a sterile lyophilized powder of albumin-bound sirolimus nanoparticles with a mean particle size of less than 100 nm.
Measure Participants	3	3	1	3	3
Count of Participants [Participants]	0 0%	1 25%	0 0%	0 0%	1 25%

Adverse Events

Time Frame	From the signing of the informed consent through the 6-week induction treatment period and the 30-day follow-up period (up to 2.5 months). An additional 4 months for patients who received 3 additional monthly maintenance treatments (up to 6.5 months).
Arm/Group Title	Phase 1: ABI-009 100 mg/Week		Phase 1: ABI-009 200 mg/Week		Phase 1: ABI-009 100 mg 2×/Week		Phase 1: ABI-009 300 mg/Week		Phase 1: ABI-009 400 mg/Week		Phase 2: ABI-009 400 mg/Week + Gemcitabine 2000 mg/Week
Arm/Group Description	Phase 1, Cohort 1: ABI-009 injectable suspension, 100 mg in 80 mL 0.9% saline, administered intravesically and retained for 2 hours, once per week for 6 weeks		Phase 1, Cohort 2: ABI-009 injectable suspension, 200 mg in 80 mL 0.9% saline, administered intravesically and retained for 2 hours, once per week for 6 weeks		Phase 1, Cohort 2b: ABI-009 injectable suspension, 100 mg in 80 mL 0.9% saline, administered intravesically and retained for 2 hours, twice per week (total dose 200 mg per week) for 6 weeks		Phase 1, Cohort 3: ABI-009 injectable suspension, 300 mg in 80 mL 0.9% saline, administered intravesically and retained for 2 hours, once per week for 6 weeks		Phase 1, Cohort 4: ABI-009 injectable suspension, 400 mg in 80 mL 0.9% saline, administered intravesically and retained for 2 hours, once per week for 6 weeks		ABI-009 injectable suspension, 200 mg in 80 mL 0.9% saline, administered intravesically and retained for 1 hour, once per week for 6 weeks; Gemcitabine, 2000 mg in 100 mL saline, administered intravesically after voiding of ABI-009 and retained for 1 hour, once per week for 6 weeks
All Cause Mortality
	Phase 1: ABI-009 100 mg/Week		Phase 1: ABI-009 200 mg/Week		Phase 1: ABI-009 100 mg 2×/Week		Phase 1: ABI-009 300 mg/Week		Phase 1: ABI-009 400 mg/Week		Phase 2: ABI-009 400 mg/Week + Gemcitabine 2000 mg/Week
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/3 (0%)		0/4 (0%)		0/1 (0%)		0/3 (0%)		0/4 (0%)		0/6 (0%)
Serious Adverse Events
	Phase 1: ABI-009 100 mg/Week		Phase 1: ABI-009 200 mg/Week		Phase 1: ABI-009 100 mg 2×/Week		Phase 1: ABI-009 300 mg/Week		Phase 1: ABI-009 400 mg/Week		Phase 2: ABI-009 400 mg/Week + Gemcitabine 2000 mg/Week
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/3 (0%)		0/4 (0%)		0/1 (0%)		0/3 (0%)		0/4 (0%)		0/6 (0%)
Other (Not Including Serious) Adverse Events
	Phase 1: ABI-009 100 mg/Week		Phase 1: ABI-009 200 mg/Week		Phase 1: ABI-009 100 mg 2×/Week		Phase 1: ABI-009 300 mg/Week		Phase 1: ABI-009 400 mg/Week		Phase 2: ABI-009 400 mg/Week + Gemcitabine 2000 mg/Week
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/3 (66.7%)		1/4 (25%)		1/1 (100%)		3/3 (100%)		3/4 (75%)		6/6 (100%)
Blood and lymphatic system disorders
Anemia	1/3 (33.3%)	1	0/4 (0%)	0	1/1 (100%)	1	1/3 (33.3%)	1	0/4 (0%)	0	1/6 (16.7%)	2
Thrombocytopenia	1/3 (33.3%)	1	0/4 (0%)	0	1/1 (100%)	2	0/3 (0%)	0	0/4 (0%)	0	0/6 (0%)	0
Decreased absolute neutrophil	0/3 (0%)	0	0/4 (0%)	0	1/1 (100%)	1	0/3 (0%)	0	0/4 (0%)	0	1/6 (16.7%)	1
Decreased white blood cell	0/3 (0%)	0	0/4 (0%)	0	1/1 (100%)	1	0/3 (0%)	0	0/4 (0%)	0	0/6 (0%)	0
Fever	0/3 (0%)	0	0/4 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/4 (0%)	0	1/6 (16.7%)	2
Cardiac disorders
Worsening of congestive heart failure	0/3 (0%)	0	0/4 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/4 (0%)	0	1/6 (16.7%)	1
Gastrointestinal disorders
Nausea	0/3 (0%)	0	0/4 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/4 (0%)	0	2/6 (33.3%)	2
General disorders
Malaise	0/3 (0%)	0	0/4 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/4 (0%)	0	1/6 (16.7%)	1
Hepatobiliary disorders
Elevated bilirubin	1/3 (33.3%)	1	0/4 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/4 (0%)	0	0/6 (0%)	0
Metabolism and nutrition disorders
Hyperglycemia	1/3 (33.3%)	1	0/4 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/4 (0%)	0	1/6 (16.7%)	1
Hyponatremia	0/3 (0%)	0	0/4 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/4 (0%)	0	1/6 (16.7%)	2
Musculoskeletal and connective tissue disorders
Worsening of edema of extremities	0/3 (0%)	0	0/4 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/4 (0%)	0	1/6 (16.7%)	3
Nervous system disorders
Headache	0/3 (0%)	0	0/4 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/4 (0%)	0	1/6 (16.7%)	1
Renal and urinary disorders
Hematuria	0/3 (0%)	0	0/4 (0%)	0	1/1 (100%)	1	2/3 (66.7%)	2	1/4 (25%)	1	0/6 (0%)	0
Urinary tract infection	0/3 (0%)	0	0/4 (0%)	0	1/1 (100%)	1	1/3 (33.3%)	1	1/4 (25%)	1	2/6 (33.3%)	2
Increased frequency and urgency of urination	1/3 (33.3%)	3	0/4 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/4 (25%)	3	1/6 (16.7%)	1
Abnormal urine analysis	0/3 (0%)	0	1/4 (25%)	1	0/1 (0%)	0	0/3 (0%)	0	0/4 (0%)	0	0/6 (0%)	0
Dysuria	0/3 (0%)	0	0/4 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/4 (25%)	2	0/6 (0%)	0
Incontinence	1/3 (33.3%)	1	0/4 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/4 (0%)	0	0/6 (0%)	0
Kidney stone	0/3 (0%)	0	0/4 (0%)	0	1/1 (100%)	1	0/3 (0%)	0	0/4 (0%)	0	0/6 (0%)	0
Elevated creatinine	1/3 (33.3%)	1	0/4 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/4 (0%)	0	0/6 (0%)	0
Bladder spasm	0/3 (0%)	0	0/4 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/4 (0%)	0	5/6 (83.3%)	21
Urinary tract pain	0/3 (0%)	0	0/4 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/4 (0%)	0	3/6 (50%)	9
Worsening of chronic kidney disease	0/3 (0%)	0	0/4 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/4 (0%)	0	1/6 (16.7%)	1
Acute kidney injury	0/3 (0%)	0	0/4 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/4 (0%)	0	1/6 (16.7%)	1
Reproductive system and breast disorders
Penis Lesion/rash	1/3 (33.3%)	1	0/4 (0%)	0	0/1 (0%)	0	1/3 (33.3%)	1	0/4 (0%)	0	0/6 (0%)	0
Prostatitis	0/3 (0%)	0	0/4 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/4 (25%)	1	0/6 (0%)	0
Respiratory, thoracic and mediastinal disorders
Cough	0/3 (0%)	0	0/4 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/4 (25%)	1	1/6 (16.7%)	1
Pleural effusion	0/3 (0%)	0	0/4 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/4 (0%)	0	1/6 (16.7%)	2
Upper respiratory tract infection	0/3 (0%)	0	0/4 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/4 (0%)	0	1/6 (16.7%)	1
Pulmonary edema	0/3 (0%)	0	0/4 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/4 (0%)	0	1/6 (16.7%)	1
Skin and subcutaneous tissue disorders
Inguinal and thigh pruritus	1/3 (33.3%)	1	0/4 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/4 (0%)	0	0/6 (0%)	0
Mucositis	0/3 (0%)	0	0/4 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/4 (0%)	0	1/6 (16.7%)	3

Limitations/Caveats

[Not Specified]

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.