Trial Outcomes & Findings for CB-839 With Everolimus vs. Placebo With Everolimus in Participants With Renal Cell Carcinoma (RCC) (NCT NCT03163667)

Last Updated: 2022-09-15

Results Overview

PFS was defined as the time from randomization to the date of documented disease progression (assessed by Investigator per Response Evaluation Criteria in Solid Tumors \[RECIST\] v1.1) within 2 scheduled scan intervals following previous evaluable radiologic tumor assessment or death for any cause, whichever occurred first. Participants with no documentation of disease progression or death on-study were censored at the date of last available tumor assessment. Progressive Disease (PD) per RECIST 1.1: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition, the sum must also demonstrate an absolute increase of at least 5 mm.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

69 participants

Primary outcome timeframe

As of the primary data cutoff date of 26 Apr 2019; maximum duration of follow-up for PFS was 11.2 months.

Results posted on

2022-09-15

Participant Flow

Participant milestones

Participant milestones
Measure	Placebo + Everolimus Placebo oral tablets twice daily (BID) in combination with standard once daily (QD) everolimus in 28 day cycles.	CB-839 + Everolimus CB-839 oral tablets BID in combination with standard QD everolimus in 28 day cycles.
Overall Study STARTED	23	46
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	23	46

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo + Everolimus Placebo oral tablets twice daily (BID) in combination with standard once daily (QD) everolimus in 28 day cycles.	CB-839 + Everolimus CB-839 oral tablets BID in combination with standard QD everolimus in 28 day cycles.
Overall Study Death	15	27
Overall Study Study terminated by sponsor (after primary endpoint was met)	8	19

Baseline Characteristics

CB-839 With Everolimus vs. Placebo With Everolimus in Participants With Renal Cell Carcinoma (RCC)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo + Everolimus n=23 Participants Placebo oral tablets BID in combination with standard QD everolimus in 28 day cycles.	CB-839 + Everolimus n=46 Participants CB-839 oral tablets BID in combination with standard QD everolimus in 28 day cycles.	Total n=69 Participants Total of all reporting groups
Age, Continuous	62.1 years STANDARD_DEVIATION 10.38 • n=5 Participants	65.8 years STANDARD_DEVIATION 9.18 • n=7 Participants	64.6 years STANDARD_DEVIATION 9.69 • n=5 Participants
Sex: Female, Male Female	3 Participants n=5 Participants	9 Participants n=7 Participants	12 Participants n=5 Participants
Sex: Female, Male Male	20 Participants n=5 Participants	37 Participants n=7 Participants	57 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	19 Participants n=5 Participants	43 Participants n=7 Participants	62 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) White	21 Participants n=5 Participants	41 Participants n=7 Participants	62 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	3 Participants n=7 Participants	3 Participants n=5 Participants

PRIMARY outcome

Timeframe: As of the primary data cutoff date of 26 Apr 2019; maximum duration of follow-up for PFS was 11.2 months.

Population: Intent to Treat Population: all randomized participants.

Outcome measures

Outcome measures
Measure	Placebo + Everolimus n=23 Participants Placebo oral tablets BID in combination with standard QD everolimus in 28 day cycles.	CB-839 + Everolimus n=46 Participants CB-839 oral tablets BID in combination with standard QD everolimus in 28 day cycles.
Progression Free Survival (PFS)	1.91 months Interval 1.87 to 8.28	3.81 months Interval 2.4 to 7.43

SECONDARY outcome

Timeframe: As of the data cutoff date of 30 Sep 2020; maximum duration of follow-up for OS was 30.4 months.

Population: ITT Population: all randomized participants.

Overall survival is defined as the time from randomization to the date of death from any cause. Participants with no documentation of death on-study were censored at the date at which they were last known to be alive.

Outcome measures

Outcome measures
Measure	Placebo + Everolimus n=23 Participants Placebo oral tablets BID in combination with standard QD everolimus in 28 day cycles.	CB-839 + Everolimus n=46 Participants CB-839 oral tablets BID in combination with standard QD everolimus in 28 day cycles.
Overall Survival (OS)	9.72 months Interval 8.21 to 25.43	14.37 months Interval 7.89 to The upper bound of 95% CI is not estimable because almost 41% of participants in this arm were censored.

Adverse Events

Placebo + Everolimus

Serious events: 8 serious events

Other events: 23 other events

Deaths: 15 deaths

CB-839 + Everolimus

Serious events: 21 serious events

Other events: 45 other events

Deaths: 27 deaths

Serious adverse events

Other adverse events

Additional Information

Study Director

Calithera Biosciences, Inc

Phone: 650-870-1000

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee No publication by the PI before either a multi-site publication or 18 months after final multi-site study report. PI can only publish their own results and provide 45 days in advance notice. PI must delete any Calithera confidential information from the publication other than study results and give good faith consideration to other comments made by Calithera. The PI must delay the publication for up to 45 days if requested by Calithera and publicly acknowledge Calithera and Pfizer support.
Publication restrictions are in place

Restriction type: OTHER

Measure	Placebo + Everolimus n=23 participants at risk Placebo oral tablets BID in combination with standard QD everolimus in 28 day cycles.	CB-839 + Everolimus n=46 participants at risk CB-839 oral tablets BID in combination with standard QD everolimus in 28 day cycles.
Respiratory, thoracic and mediastinal disorders Pneumonitis	0.00% 0/23 • From the first dose of study drug through the end of treatment plus 28 days. The mean duration of exposure of CB-839 was 161.3 days and the mean duration of exposure for placebo was 176.2 days.	4.3% 2/46 • From the first dose of study drug through the end of treatment plus 28 days. The mean duration of exposure of CB-839 was 161.3 days and the mean duration of exposure for placebo was 176.2 days.
Respiratory, thoracic and mediastinal disorders Dyspnoea	4.3% 1/23 • From the first dose of study drug through the end of treatment plus 28 days. The mean duration of exposure of CB-839 was 161.3 days and the mean duration of exposure for placebo was 176.2 days.	2.2% 1/46 • From the first dose of study drug through the end of treatment plus 28 days. The mean duration of exposure of CB-839 was 161.3 days and the mean duration of exposure for placebo was 176.2 days.
Respiratory, thoracic and mediastinal disorders Hypoxia	0.00% 0/23 • From the first dose of study drug through the end of treatment plus 28 days. The mean duration of exposure of CB-839 was 161.3 days and the mean duration of exposure for placebo was 176.2 days.	2.2% 1/46 • From the first dose of study drug through the end of treatment plus 28 days. The mean duration of exposure of CB-839 was 161.3 days and the mean duration of exposure for placebo was 176.2 days.
Respiratory, thoracic and mediastinal disorders Pleural effusion	4.3% 1/23 • From the first dose of study drug through the end of treatment plus 28 days. The mean duration of exposure of CB-839 was 161.3 days and the mean duration of exposure for placebo was 176.2 days.	2.2% 1/46 • From the first dose of study drug through the end of treatment plus 28 days. The mean duration of exposure of CB-839 was 161.3 days and the mean duration of exposure for placebo was 176.2 days.
Respiratory, thoracic and mediastinal disorders Respiratory distress	0.00% 0/23 • From the first dose of study drug through the end of treatment plus 28 days. The mean duration of exposure of CB-839 was 161.3 days and the mean duration of exposure for placebo was 176.2 days.	2.2% 1/46 • From the first dose of study drug through the end of treatment plus 28 days. The mean duration of exposure of CB-839 was 161.3 days and the mean duration of exposure for placebo was 176.2 days.
Respiratory, thoracic and mediastinal disorders Respiratory failure	4.3% 1/23 • From the first dose of study drug through the end of treatment plus 28 days. The mean duration of exposure of CB-839 was 161.3 days and the mean duration of exposure for placebo was 176.2 days.	0.00% 0/46 • From the first dose of study drug through the end of treatment plus 28 days. The mean duration of exposure of CB-839 was 161.3 days and the mean duration of exposure for placebo was 176.2 days.
Infections and infestations Pneumonia	4.3% 1/23 • From the first dose of study drug through the end of treatment plus 28 days. The mean duration of exposure of CB-839 was 161.3 days and the mean duration of exposure for placebo was 176.2 days.	6.5% 3/46 • From the first dose of study drug through the end of treatment plus 28 days. The mean duration of exposure of CB-839 was 161.3 days and the mean duration of exposure for placebo was 176.2 days.
Infections and infestations Lung infection	0.00% 0/23 • From the first dose of study drug through the end of treatment plus 28 days. The mean duration of exposure of CB-839 was 161.3 days and the mean duration of exposure for placebo was 176.2 days.	2.2% 1/46 • From the first dose of study drug through the end of treatment plus 28 days. The mean duration of exposure of CB-839 was 161.3 days and the mean duration of exposure for placebo was 176.2 days.
Infections and infestations Parotitis	0.00% 0/23 • From the first dose of study drug through the end of treatment plus 28 days. The mean duration of exposure of CB-839 was 161.3 days and the mean duration of exposure for placebo was 176.2 days.	2.2% 1/46 • From the first dose of study drug through the end of treatment plus 28 days. The mean duration of exposure of CB-839 was 161.3 days and the mean duration of exposure for placebo was 176.2 days.
Infections and infestations Streptococcal sepsis	0.00% 0/23 • From the first dose of study drug through the end of treatment plus 28 days. The mean duration of exposure of CB-839 was 161.3 days and the mean duration of exposure for placebo was 176.2 days.	2.2% 1/46 • From the first dose of study drug through the end of treatment plus 28 days. The mean duration of exposure of CB-839 was 161.3 days and the mean duration of exposure for placebo was 176.2 days.
Infections and infestations Urinary tract infection	0.00% 0/23 • From the first dose of study drug through the end of treatment plus 28 days. The mean duration of exposure of CB-839 was 161.3 days and the mean duration of exposure for placebo was 176.2 days.	2.2% 1/46 • From the first dose of study drug through the end of treatment plus 28 days. The mean duration of exposure of CB-839 was 161.3 days and the mean duration of exposure for placebo was 176.2 days.
Infections and infestations Sepsis	4.3% 1/23 • From the first dose of study drug through the end of treatment plus 28 days. The mean duration of exposure of CB-839 was 161.3 days and the mean duration of exposure for placebo was 176.2 days.	0.00% 0/46 • From the first dose of study drug through the end of treatment plus 28 days. The mean duration of exposure of CB-839 was 161.3 days and the mean duration of exposure for placebo was 176.2 days.
Nervous system disorders Dizziness	0.00% 0/23 • From the first dose of study drug through the end of treatment plus 28 days. The mean duration of exposure of CB-839 was 161.3 days and the mean duration of exposure for placebo was 176.2 days.	10.9% 5/46 • From the first dose of study drug through the end of treatment plus 28 days. The mean duration of exposure of CB-839 was 161.3 days and the mean duration of exposure for placebo was 176.2 days.
Nervous system disorders Paraesthesia	0.00% 0/23 • From the first dose of study drug through the end of treatment plus 28 days. The mean duration of exposure of CB-839 was 161.3 days and the mean duration of exposure for placebo was 176.2 days.	2.2% 1/46 • From the first dose of study drug through the end of treatment plus 28 days. The mean duration of exposure of CB-839 was 161.3 days and the mean duration of exposure for placebo was 176.2 days.
Nervous system disorders Transient ischaemic attack	0.00% 0/23 • From the first dose of study drug through the end of treatment plus 28 days. The mean duration of exposure of CB-839 was 161.3 days and the mean duration of exposure for placebo was 176.2 days.	2.2% 1/46 • From the first dose of study drug through the end of treatment plus 28 days. The mean duration of exposure of CB-839 was 161.3 days and the mean duration of exposure for placebo was 176.2 days.
Nervous system disorders Vasogenic cerebral oedema	0.00% 0/23 • From the first dose of study drug through the end of treatment plus 28 days. The mean duration of exposure of CB-839 was 161.3 days and the mean duration of exposure for placebo was 176.2 days.	2.2% 1/46 • From the first dose of study drug through the end of treatment plus 28 days. The mean duration of exposure of CB-839 was 161.3 days and the mean duration of exposure for placebo was 176.2 days.
Gastrointestinal disorders Abdominal pain	0.00% 0/23 • From the first dose of study drug through the end of treatment plus 28 days. The mean duration of exposure of CB-839 was 161.3 days and the mean duration of exposure for placebo was 176.2 days.	4.3% 2/46 • From the first dose of study drug through the end of treatment plus 28 days. The mean duration of exposure of CB-839 was 161.3 days and the mean duration of exposure for placebo was 176.2 days.
Gastrointestinal disorders Abdominal pain upper	0.00% 0/23 • From the first dose of study drug through the end of treatment plus 28 days. The mean duration of exposure of CB-839 was 161.3 days and the mean duration of exposure for placebo was 176.2 days.	2.2% 1/46 • From the first dose of study drug through the end of treatment plus 28 days. The mean duration of exposure of CB-839 was 161.3 days and the mean duration of exposure for placebo was 176.2 days.
Gastrointestinal disorders Diarrhoea	0.00% 0/23 • From the first dose of study drug through the end of treatment plus 28 days. The mean duration of exposure of CB-839 was 161.3 days and the mean duration of exposure for placebo was 176.2 days.	2.2% 1/46 • From the first dose of study drug through the end of treatment plus 28 days. The mean duration of exposure of CB-839 was 161.3 days and the mean duration of exposure for placebo was 176.2 days.
Gastrointestinal disorders Nausea	0.00% 0/23 • From the first dose of study drug through the end of treatment plus 28 days. The mean duration of exposure of CB-839 was 161.3 days and the mean duration of exposure for placebo was 176.2 days.	2.2% 1/46 • From the first dose of study drug through the end of treatment plus 28 days. The mean duration of exposure of CB-839 was 161.3 days and the mean duration of exposure for placebo was 176.2 days.
Gastrointestinal disorders Vomiting	0.00% 0/23 • From the first dose of study drug through the end of treatment plus 28 days. The mean duration of exposure of CB-839 was 161.3 days and the mean duration of exposure for placebo was 176.2 days.	2.2% 1/46 • From the first dose of study drug through the end of treatment plus 28 days. The mean duration of exposure of CB-839 was 161.3 days and the mean duration of exposure for placebo was 176.2 days.
Gastrointestinal disorders Small intestinal haemorrhage	4.3% 1/23 • From the first dose of study drug through the end of treatment plus 28 days. The mean duration of exposure of CB-839 was 161.3 days and the mean duration of exposure for placebo was 176.2 days.	0.00% 0/46 • From the first dose of study drug through the end of treatment plus 28 days. The mean duration of exposure of CB-839 was 161.3 days and the mean duration of exposure for placebo was 176.2 days.
Gastrointestinal disorders Upper gastrointestinal haemorrhage	4.3% 1/23 • From the first dose of study drug through the end of treatment plus 28 days. The mean duration of exposure of CB-839 was 161.3 days and the mean duration of exposure for placebo was 176.2 days.	0.00% 0/46 • From the first dose of study drug through the end of treatment plus 28 days. The mean duration of exposure of CB-839 was 161.3 days and the mean duration of exposure for placebo was 176.2 days.
Blood and lymphatic system disorders Anaemia	8.7% 2/23 • From the first dose of study drug through the end of treatment plus 28 days. The mean duration of exposure of CB-839 was 161.3 days and the mean duration of exposure for placebo was 176.2 days.	4.3% 2/46 • From the first dose of study drug through the end of treatment plus 28 days. The mean duration of exposure of CB-839 was 161.3 days and the mean duration of exposure for placebo was 176.2 days.
Cardiac disorders Cardiac failure congestive	0.00% 0/23 • From the first dose of study drug through the end of treatment plus 28 days. The mean duration of exposure of CB-839 was 161.3 days and the mean duration of exposure for placebo was 176.2 days.	2.2% 1/46 • From the first dose of study drug through the end of treatment plus 28 days. The mean duration of exposure of CB-839 was 161.3 days and the mean duration of exposure for placebo was 176.2 days.
Cardiac disorders Cardio-respiratory arrest	4.3% 1/23 • From the first dose of study drug through the end of treatment plus 28 days. The mean duration of exposure of CB-839 was 161.3 days and the mean duration of exposure for placebo was 176.2 days.	2.2% 1/46 • From the first dose of study drug through the end of treatment plus 28 days. The mean duration of exposure of CB-839 was 161.3 days and the mean duration of exposure for placebo was 176.2 days.
General disorders Gait disturbance	0.00% 0/23 • From the first dose of study drug through the end of treatment plus 28 days. The mean duration of exposure of CB-839 was 161.3 days and the mean duration of exposure for placebo was 176.2 days.	2.2% 1/46 • From the first dose of study drug through the end of treatment plus 28 days. The mean duration of exposure of CB-839 was 161.3 days and the mean duration of exposure for placebo was 176.2 days.
General disorders Oedema peripheral	0.00% 0/23 • From the first dose of study drug through the end of treatment plus 28 days. The mean duration of exposure of CB-839 was 161.3 days and the mean duration of exposure for placebo was 176.2 days.	2.2% 1/46 • From the first dose of study drug through the end of treatment plus 28 days. The mean duration of exposure of CB-839 was 161.3 days and the mean duration of exposure for placebo was 176.2 days.
General disorders Fatigue	4.3% 1/23 • From the first dose of study drug through the end of treatment plus 28 days. The mean duration of exposure of CB-839 was 161.3 days and the mean duration of exposure for placebo was 176.2 days.	0.00% 0/46 • From the first dose of study drug through the end of treatment plus 28 days. The mean duration of exposure of CB-839 was 161.3 days and the mean duration of exposure for placebo was 176.2 days.
Injury, poisoning and procedural complications Overdose	0.00% 0/23 • From the first dose of study drug through the end of treatment plus 28 days. The mean duration of exposure of CB-839 was 161.3 days and the mean duration of exposure for placebo was 176.2 days.	2.2% 1/46 • From the first dose of study drug through the end of treatment plus 28 days. The mean duration of exposure of CB-839 was 161.3 days and the mean duration of exposure for placebo was 176.2 days.
Injury, poisoning and procedural complications Pubis fracture	0.00% 0/23 • From the first dose of study drug through the end of treatment plus 28 days. The mean duration of exposure of CB-839 was 161.3 days and the mean duration of exposure for placebo was 176.2 days.	2.2% 1/46 • From the first dose of study drug through the end of treatment plus 28 days. The mean duration of exposure of CB-839 was 161.3 days and the mean duration of exposure for placebo was 176.2 days.
Renal and urinary disorders Acute kidney injury	0.00% 0/23 • From the first dose of study drug through the end of treatment plus 28 days. The mean duration of exposure of CB-839 was 161.3 days and the mean duration of exposure for placebo was 176.2 days.	4.3% 2/46 • From the first dose of study drug through the end of treatment plus 28 days. The mean duration of exposure of CB-839 was 161.3 days and the mean duration of exposure for placebo was 176.2 days.
Eye disorders Vision blurred	0.00% 0/23 • From the first dose of study drug through the end of treatment plus 28 days. The mean duration of exposure of CB-839 was 161.3 days and the mean duration of exposure for placebo was 176.2 days.	2.2% 1/46 • From the first dose of study drug through the end of treatment plus 28 days. The mean duration of exposure of CB-839 was 161.3 days and the mean duration of exposure for placebo was 176.2 days.
Hepatobiliary disorders Cholecystitis	0.00% 0/23 • From the first dose of study drug through the end of treatment plus 28 days. The mean duration of exposure of CB-839 was 161.3 days and the mean duration of exposure for placebo was 176.2 days.	2.2% 1/46 • From the first dose of study drug through the end of treatment plus 28 days. The mean duration of exposure of CB-839 was 161.3 days and the mean duration of exposure for placebo was 176.2 days.
Investigations Blood creatinine increased	0.00% 0/23 • From the first dose of study drug through the end of treatment plus 28 days. The mean duration of exposure of CB-839 was 161.3 days and the mean duration of exposure for placebo was 176.2 days.	2.2% 1/46 • From the first dose of study drug through the end of treatment plus 28 days. The mean duration of exposure of CB-839 was 161.3 days and the mean duration of exposure for placebo was 176.2 days.
Metabolism and nutrition disorders Hyperkalaemia	0.00% 0/23 • From the first dose of study drug through the end of treatment plus 28 days. The mean duration of exposure of CB-839 was 161.3 days and the mean duration of exposure for placebo was 176.2 days.	2.2% 1/46 • From the first dose of study drug through the end of treatment plus 28 days. The mean duration of exposure of CB-839 was 161.3 days and the mean duration of exposure for placebo was 176.2 days.
Metabolism and nutrition disorders Hypercalcaemia	4.3% 1/23 • From the first dose of study drug through the end of treatment plus 28 days. The mean duration of exposure of CB-839 was 161.3 days and the mean duration of exposure for placebo was 176.2 days.	0.00% 0/46 • From the first dose of study drug through the end of treatment plus 28 days. The mean duration of exposure of CB-839 was 161.3 days and the mean duration of exposure for placebo was 176.2 days.
Musculoskeletal and connective tissue disorders Flank pain	0.00% 0/23 • From the first dose of study drug through the end of treatment plus 28 days. The mean duration of exposure of CB-839 was 161.3 days and the mean duration of exposure for placebo was 176.2 days.	2.2% 1/46 • From the first dose of study drug through the end of treatment plus 28 days. The mean duration of exposure of CB-839 was 161.3 days and the mean duration of exposure for placebo was 176.2 days.
Psychiatric disorders Mental status changes	0.00% 0/23 • From the first dose of study drug through the end of treatment plus 28 days. The mean duration of exposure of CB-839 was 161.3 days and the mean duration of exposure for placebo was 176.2 days.	2.2% 1/46 • From the first dose of study drug through the end of treatment plus 28 days. The mean duration of exposure of CB-839 was 161.3 days and the mean duration of exposure for placebo was 176.2 days.
Psychiatric disorders Confusional state	4.3% 1/23 • From the first dose of study drug through the end of treatment plus 28 days. The mean duration of exposure of CB-839 was 161.3 days and the mean duration of exposure for placebo was 176.2 days.	0.00% 0/46 • From the first dose of study drug through the end of treatment plus 28 days. The mean duration of exposure of CB-839 was 161.3 days and the mean duration of exposure for placebo was 176.2 days.
Vascular disorders Hypertension	0.00% 0/23 • From the first dose of study drug through the end of treatment plus 28 days. The mean duration of exposure of CB-839 was 161.3 days and the mean duration of exposure for placebo was 176.2 days.	2.2% 1/46 • From the first dose of study drug through the end of treatment plus 28 days. The mean duration of exposure of CB-839 was 161.3 days and the mean duration of exposure for placebo was 176.2 days.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to central nervous system	4.3% 1/23 • From the first dose of study drug through the end of treatment plus 28 days. The mean duration of exposure of CB-839 was 161.3 days and the mean duration of exposure for placebo was 176.2 days.	0.00% 0/46 • From the first dose of study drug through the end of treatment plus 28 days. The mean duration of exposure of CB-839 was 161.3 days and the mean duration of exposure for placebo was 176.2 days.