Combination Treatment (Talazoparib Plus Avelumab) for Stage IV or Recurrent Non-Squamous Non-Small Cell Lung Cancer With STK11 Gene Mutation (A LUNG-MAP Treatment Trial)

• ClinicalTrials.gov Identifier: NCT04173507
• Recruitment Status: Active, not recruiting
• First Posted: November 22, 2019
• Results First Posted: January 9, 2023
• Last Update Posted: January 9, 2023
• Sponsor: Southwest Oncology Group
• Collaborator: National Cancer Institute (NCI)
• Information provided by (Responsible Party): Southwest Oncology Group

• Study Type: Interventional
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Conditions: Advanced Lung Non-Squamous Non-Small Cell Carcinoma; Recurrent Lung Non-Squamous Non-Small Cell Carcinoma; Stage IV Lung Cancer AJCC v8; Stage IVA Lung Cancer AJCC v8; Stage IVB Lung Cancer AJCC v8
• Interventions: Drug: Avelumab; Drug: Talazoparib; Drug: Talazoparib Tosylate
• Enrollment: 47

Participant Flow

Recruitment Details
Pre-assignment Details	47 participants were initially registered. Five participants were ineligible. In all, 42 participants were eligible and received protocol therapy.

Arm/Group Title	Talazoparib Plus Avelumab
Arm/Group Description	Participants receive talazoparib PO daily and avelumab IV over 60 minutes on days 1 and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Talazoparib: Given PO Avelumab: Given IV
Period Title: Overall Study
Started	42
Completed	0
Not Completed	42
Reason Not Completed
On Treatment	3
Adverse Event	3
Progression/Relapse	34
Death	2

Baseline Characteristics

Arm/Group Title		Talazoparib Plus Avelumab
Arm/Group Description		Participants receive talazoparib PO daily and avelumab IV over 60 minutes on days 1 and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Talazoparib: Given PO Avelumab: Given IV
Overall Number of Baseline Participants		42
Baseline Analysis Population Description		Eligible participants
Age, Continuous; Median (Full Range); Unit of measure: Years
	Number Analyzed	42 participants
		63.8; (36.8 to 83.5)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	42 participants
	Female	21 50.0%
	Male	21 50.0%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	42 participants
	Hispanic or Latino	1 2.4%
	Not Hispanic or Latino	41 97.6%
	Unknown or Not Reported	0 0.0%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	42 participants
	American Indian or Alaska Native	1 2.4%
	Asian	1 2.4%
	Native Hawaiian or Other Pacific Islander	0 0.0%
	Black or African American	11 26.2%
	White	29 69.0%
	More than one race	0 0.0%
	Unknown or Not Reported	0 0.0%
Prior Lines of Treatment for Stage IV Disease; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	42 participants
	0	4 9.5%
	1	16 38.1%
	2 or more	22 52.4%
Performance Status [1]; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	42 participants
	0	10 23.8%
	1	32 76.2%
		[1] Measure Description: Participants were graded according to the Zubrod Performance Status Scale. 0 - Fully active, able to carry out on all pre-disease performance without restriction. 1 - Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g. light housework, office work.
Weight Loss in the Past 6 Months; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	42 participants
	< 5%	25 59.5%
	5 - < 10%	12 28.6%
	10 - < 20%	3 7.1%
	Unknown	2 4.8%
Smoking Status; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	42 participants
	Current Smoker	17 40.5%
	Former Smoker	23 54.8%
	Never Smoker	2 4.8%
Histology; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	42 participants
	Adenocarcinoma	36 85.7%
	Other non-small cell, NOS	6 14.3%

Outcome Measures

1. Primary Outcome

Title	Objective Response Rate (ORR)
Description	Percentage of participants with confirmed or unconfirmed, complete or partial response to treatment with talazoparib plus avelumab per Response Evaluation Criteria in Solid Tumors (RECIST 1.1) criteria. Complete Response (CR): Complete disappearance of all target and non-target lesions. No new lesions. No disease related symptoms. Any lymph nodes (whether target or non-target) must have reduction in short axis to < 1.0 cm. All disease must be assessed using the same technique as baseline. Partial Response (PR): Applies only to participants with at least one measurable lesion. Greater than or equal to 30% decrease under baseline of the sum of appropriate diameters of all target measurable lesions. No unequivocal progression of non-measurable disease. No new lesions. All target measurable lesions must be assessed using the same techniques as baseline.
Time Frame	From date of registration to progression or treatment discontinuation, up to 1 year and 9 months

Outcome Measure Data

Analysis Population Description

Eligible and evaluable participants

Arm/Group Title	Talazoparib Plus Avelumab
Arm/Group Description:	Participants receive talazoparib PO daily and avelumab IV over 60 minutes on days 1 and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Talazoparib: Given PO Avelumab: Given IV
Overall Number of Participants Analyzed	42
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	2; (0 to 7)

2. Primary Outcome

Title	Disease Control Rate at 12 Weeks (DCR12)
Description	Percentage of participants with a best response of Complete Response (CR), Partial Response (PR), Unconfirmed Partial Response (UPR), or Unconfirmed Complete Response (UCR) by/at the second disease assessment at 12 weeks after registration (+/- 2 weeks), or stable disease at 12 weeks after registration (+/- 2 weeks). Participants with missing or delayed disease assessment at 12 weeks (+/- 2 weeks), at or before the disease assessment at 20 weeks (+/- 2 weeks) with documented lack of progression (CR, PR, UPR, UCR, or stable) were coded as having disease control at 12 weeks. Participants not known to have disease control at 12 weeks who have at least 12 weeks of follow-up were coded as not having disease control at 12 weeks.
Time Frame	12 weeks after registration

Outcome Measure Data

Analysis Population Description

Eligible and evaluable participants

Arm/Group Title	Talazoparib Plus Avelumab
Arm/Group Description:	Participants receive talazoparib PO daily and avelumab IV over 60 minutes on days 1 and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Talazoparib: Given PO Avelumab: Given IV
Overall Number of Participants Analyzed	42
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	40; (26 to 55)

3. Secondary Outcome

Title	Investigator-Assessed Progression-Free Survival (IA-PFS)
Description	From date of sub-study registration to date of first documentation of progression assessed by local review or symptomatic deterioration, or death due to any cause. Participants last known to be alive without report of progression are censored at date of last disease assessment. For participants with a missing scan (or consecutive missing scans) whose subsequent scan determines progression, the expected date of the first missing scan (as defined by the disease assessment schedule) is used as the date of progression. Progression is defined as: 20% increase in the sum of appropriate diameters of target lesions and absolute increase of at least 0.5 cm, or unequivocal progression of non-measurable disease, or appearance of any new lesion/site, or death from disease without prior documentation of progression or symptomatic deterioration. Symptomatic deterioration: Global deterioration of health status requiring discontinuation of treatment without objective evidence of progression.
Time Frame	From date of registration to a maximum of 3 years or death

Outcome Measure Data

Analysis Population Description

Eligible and evaluable participants

Arm/Group Title	Talazoparib Plus Avelumab
Arm/Group Description:	Participants receive talazoparib PO daily and avelumab IV over 60 minutes on days 1 and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Talazoparib: Given PO Avelumab: Given IV
Overall Number of Participants Analyzed	42
Median (95% Confidence Interval); Unit of Measure: months
	2.7; (1.6 to 3.9)

4. Secondary Outcome

Title	Overall Survival (OS)
Description	From date of sub-study registration to date of death due to any cause. Participants last known to be alive are censored at date of last contact.
Time Frame	From date of registration to a maximum of 3 years or death

Outcome Measure Data

Analysis Population Description

Eligible and evaluable participants

Arm/Group Title	Talazoparib Plus Avelumab
Arm/Group Description:	Participants receive talazoparib PO daily and avelumab IV over 60 minutes on days 1 and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Talazoparib: Given PO Avelumab: Given IV
Overall Number of Participants Analyzed	42
Median (95% Confidence Interval); Unit of Measure: months
	7.6; (6.3 to 12.2)

5. Secondary Outcome

Title	Duration of Response (DOR)
Description	From date of first response to first progression assessed by local review or symptomatic deterioration, or death among patients with a response (CR or PR). Those last known to be alive without progression are censored at date of last disease assessment. For those with a missing scan whose next scan shows progression, expected date of the first missing scan is used as progression date. Complete Response (CR): Disappearance of all target and non-target lesions. No new lesions or disease related symptoms. Lymph nodes must have reduction in short axis to < 1.0cm. Assessed using same technique as baseline. Partial Response (PR): At least 30% decrease under baseline of the sum of appropriate diameters of all target measurable lesions. No unequivocal progression of non-measurable disease. No new lesions. Assessed using same technique as baseline. Symptomatic deterioration: Global deterioration of health status requiring discontinuation of treatment w/o objective evidence of progression.
Time Frame	From date of registration to a maximum of 3 years or death

Outcome Measure Data

Analysis Population Description

Participant with a complete or partial response. As only one participant achieved a response, outcome data is entered as a single number rather than a median.

Arm/Group Title	Talazoparib Plus Avelumab
Arm/Group Description:	Participants receive talazoparib PO daily and avelumab IV over 60 minutes on days 1 and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Talazoparib: Given PO Avelumab: Given IV
Overall Number of Participants Analyzed	1
Measure Type: Number; Unit of Measure: months
	7.3

6. Secondary Outcome

Title	Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs
Description	Only adverse events that are possibly, probably or definitely related to study drug are reported. CTCAE Version 5.0 was used for routine toxicity reporting and serious adverse events (SAEs).
Time Frame	Duration of treatment and follow up until death or 3 years post registration

Outcome Measure Data

Analysis Population Description

Eligible participants who received at least one dose of protocol treatment

Arm/Group Title	Talazoparib Plus Avelumab
Arm/Group Description:	Participants receive talazoparib PO daily and avelumab IV over 60 minutes on days 1 and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Talazoparib: Given PO Avelumab: Given IV
Overall Number of Participants Analyzed	42
Measure Type: Number; Unit of Measure: Participants
Anemia	12
Anorexia	1
Atrial flutter	1
Fatigue	1
Febrile neutropenia	1
Generalized muscle weakness	1
Hypokalemia	1
Hyponatremia	1
Hypoxia	1
Lung infection	2
Lymphocyte count decreased	5
Metabolism and nutrition disorders - Other, specify	1
Neutrophil count decreased	1
Non-cardiac chest pain	1
Pain	1
Pain in extremity	1
Platelet count decreased	7
White blood cell decreased	2

Adverse Events

Time Frame	Duration of treatment and follow-up until death or 3 years post registration
Adverse Event Reporting Description	CTCAE Version 5.0 was used for routine toxicity reporting and Serious Adverse Event (SAE) reporting. 42 participants were assessed for adverse events.
Arm/Group Title	Talazoparib Plus Avelumab
Arm/Group Description	Participants receive talazoparib PO daily and avelumab IV over 60 minutes on days 1 and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Talazoparib: Given PO Avelumab: Given IV
All-Cause Mortality
	Talazoparib Plus Avelumab
	Affected / at Risk (%)
Total	30/42 (71.43%)
Serious Adverse Events
	Talazoparib Plus Avelumab
	Affected / at Risk (%)
Total	15/42 (35.71%)
Blood and lymphatic system disorders
Anemia †	8/42 (19.05%)
Febrile neutropenia †	1/42 (2.38%)
Cardiac disorders
Atrial flutter †	1/42 (2.38%)
Sinus tachycardia †	1/42 (2.38%)
Gastrointestinal disorders
Abdominal pain †	1/42 (2.38%)
Nausea †	1/42 (2.38%)
Vomiting †	1/42 (2.38%)
General disorders
Death NOS †	1/42 (2.38%)
Disease progression †	2/42 (4.76%)
Non-cardiac chest pain †	1/42 (2.38%)
Infections and infestations
Lung infection †	1/42 (2.38%)
Injury, poisoning and procedural complications
Fall †	1/42 (2.38%)
Investigations
Creatinine increased †	1/42 (2.38%)
Lymphocyte count decreased †	1/42 (2.38%)
Platelet count decreased †	4/42 (9.52%)
White blood cell decreased †	1/42 (2.38%)
Metabolism and nutrition disorders
Hypokalemia †	1/42 (2.38%)
Metabolism and nutrition disorders-Other †	1/42 (2.38%)
Nervous system disorders
Headache †	1/42 (2.38%)
Nervous system disorders-Other †	1/42 (2.38%)
Respiratory, thoracic and mediastinal disorders
Dyspnea †	1/42 (2.38%)
Pneumothorax †	1/42 (2.38%)
Respiratory failure †	2/42 (4.76%)
Skin and subcutaneous tissue disorders
Rash maculo-papular †	1/42 (2.38%)
Vascular disorders
Superior vena cava syndrome †	1/42 (2.38%)
† Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Talazoparib Plus Avelumab
	Affected / at Risk (%)
Total	41/42 (97.62%)
Blood and lymphatic system disorders
Anemia †	25/42 (59.52%)
Gastrointestinal disorders
Abdominal pain †	3/42 (7.14%)
Constipation †	6/42 (14.29%)
Diarrhea †	13/42 (30.95%)
Dry mouth †	4/42 (9.52%)
Dyspepsia †	3/42 (7.14%)
Dysphagia †	3/42 (7.14%)
Nausea †	15/42 (35.71%)
Toothache †	3/42 (7.14%)
Vomiting †	8/42 (19.05%)
General disorders
Chills †	4/42 (9.52%)
Fatigue †	23/42 (54.76%)
Fever †	3/42 (7.14%)
Non-cardiac chest pain †	3/42 (7.14%)
Pain †	9/42 (21.43%)
Injury, poisoning and procedural complications
Infusion related reaction †	5/42 (11.90%)
Investigations
Alanine aminotransferase increased †	3/42 (7.14%)
Alkaline phosphatase increased †	9/42 (21.43%)
Aspartate aminotransferase increased †	4/42 (9.52%)
Creatinine increased †	4/42 (9.52%)
Lymphocyte count decreased †	12/42 (28.57%)
Neutrophil count decreased †	10/42 (23.81%)
Platelet count decreased †	17/42 (40.48%)
Weight loss †	13/42 (30.95%)
White blood cell decreased †	13/42 (30.95%)
Metabolism and nutrition disorders
Anorexia †	12/42 (28.57%)
Dehydration †	5/42 (11.90%)
Hyperglycemia †	5/42 (11.90%)
Hypoalbuminemia †	8/42 (19.05%)
Hypokalemia †	7/42 (16.67%)
Hyponatremia †	7/42 (16.67%)
Musculoskeletal and connective tissue disorders
Generalized muscle weakness †	3/42 (7.14%)
Myalgia †	3/42 (7.14%)
Pain in extremity †	5/42 (11.90%)
Nervous system disorders
Dizziness †	6/42 (14.29%)
Dysgeusia †	4/42 (9.52%)
Headache †	6/42 (14.29%)
Paresthesia †	3/42 (7.14%)
Peripheral sensory neuropathy †	6/42 (14.29%)
Psychiatric disorders
Insomnia †	4/42 (9.52%)
Respiratory, thoracic and mediastinal disorders
Cough †	9/42 (21.43%)
Dyspnea †	9/42 (21.43%)
Epistaxis †	3/42 (7.14%)
Pneumonitis †	3/42 (7.14%)
Skin and subcutaneous tissue disorders
Alopecia †	3/42 (7.14%)
Dry skin †	3/42 (7.14%)
Pruritus †	6/42 (14.29%)
Rash maculo-papular †	4/42 (9.52%)
Vascular disorders
Hypertension †	5/42 (11.90%)
Hypotension †	6/42 (14.29%)
† Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

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

There IS 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.

Results Point of Contact

• Name/Title: Lung Committee Statistician
• Organization: SWOG Statistics and Data Management Center
• Phone: 2066674623
• EMail: kmini@fredhutch.org

• Responsible Party: Southwest Oncology Group
• ClinicalTrials.gov Identifier: NCT04173507
• Other Study ID Numbers: S1900C; NCI-2019-07142 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ); S1900C ( Other Identifier: SWOG ); S1900C ( Other Identifier: CTEP ); U10CA180888 ( U.S. NIH Grant/Contract )
• First Submitted: November 20, 2019
• First Posted: November 22, 2019
• Results First Submitted: October 18, 2022
• Results First Posted: January 9, 2023
• Last Update Posted: January 9, 2023