A Phase II Study of Talazoparib Plus Avelumab in Patients With Stage IV or Recurrent Non-Squamous Non-Small Cell Lung Cancer Bearing Pathogenic STK11 Genomic Alterations (LUNG-MAP Sub-Study)
Overview
- Phase
- Phase 2
- Intervention
- Talazoparib Tosylate
- Conditions
- Advanced Lung Non-Squamous Non-Small Cell Carcinoma
- Sponsor
- SWOG Cancer Research Network
- Enrollment
- 47
- Locations
- 325
- Primary Endpoint
- Disease Control Rate at 12 Weeks (DCR12)
- Status
- Active, not recruiting
- Last Updated
- last year
Overview
Brief Summary
This phase II LUNG-MAP treatment trial studies how well combination treatment (talazoparib plus avelumab) works in treating patients with non-squamous non-small cell lung cancer that has an STK11 gene mutation and has come back (recurrent) or is stage IV. Talazoparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as avelumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Immunotherapy drugs given as single therapies or in combination with chemotherapy do not appear to work as well in lung cancer cells with mutations in the STK11 gene versus those that do not have the mutation. Adding the medicine talazoparib to the immunotherapy drug avelumab may work better in treating lung cancers that have an STK11 gene mutation.
Detailed Description
PRIMARY OBJECTIVES: I. To evaluate the objective response rate (ORR) (confirmed and unconfirmed, complete and partial) with talazoparib plus avelumab in patients with stage IV or recurrent non-squamous non-small cell lung cancer bearing pathogenic STK11 genomic alterations that were previously-treated with anti-PD-1/PD-L1 therapy and platinum-based chemotherapy. II. To evaluate disease control rate at 12 weeks (DCR12) after registration. SECONDARY OBJECTIVES: I. To evaluate investigator assessed progression-free survival (IA-PFS). II. To evaluate overall survival (OS). III. To evaluate duration of response (DOR) among responders. IV. To evaluate the frequency and severity of toxicities. TRANSLATIONAL MEDICINE OBJECTIVES: I. To collect, process, and bank cell-free deoxyribonucleic acid (DNA) (cfDNA) at baseline, cycle 3 day 1, progression, and end of treatment for future development of a proposal to evaluate comprehensive next-generation sequencing of circulating tumor DNA (ctDNA) and examine molecular mechanisms of resistance to talazoparib and avelumab. II. To establish a tissue/blood repository from patients with refractory non-small cell lung cancer (NSCLC). III. To evaluate clinical outcomes (ORR, IA-PFS, OS) in patients with concurrent somatic mutations in KEAP1 detected on the Foundation Medicine Inc. (FMI) panel from the LUNGMAP screening protocol. IV. To evaluate clinical outcomes (ORR, IA-PFS, OS) in patients with concurrent mutations in ATM or other DNA damage response genes detected on the FMI panel from the LUNGMAP screening protocol. V. To evaluate the association between tumor mutational burden (TMB) measured on the FMI panel from the LUNGMAP screening protocol and clinical outcomes (ORR, IA-PFS, OS). OUTLINE: Patients receive talazoparib orally (PO) daily and avelumab intravenously (IV) over 60 minutes on days 1 and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up until death or 3 years after sub-study registration.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Patients must be assigned to S1900C. Assignment to S1900C is determined by the LUNGMAP protocol genomic profiling using the FoundationOne assay. Biomarker eligibility for S1900C is based on the identification of a pathogenic somatic mutation in STK11 or STK11 bi-allelic loss on tumor
- •Patients must have histologically or cytologically confirmed stage IV or recurrent non-squamous, mixed squamous/non-squamous (e.g., adeno-squamous carcinoma), or non-small cell lung cancer not otherwise specified (NSCLC NOS). Patients with pure squamous cell carcinoma are not eligible
- •Patients with evidence of chronic hepatitis B virus (HBV) infection must have undetectable HBV viral load on suppressive therapy within 28 days prior to sub-study registration
- •Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. Patients with HCV infection who are currently on treatment must have an undetectable HCV viral load within 28 days prior to sub-study registration
- •Patients with known human immunodeficiency virus (HIV) infection are eligible, provided they are on effective anti-retroviral therapy and have undetectable viral load at their most recent viral load test and within 6 months prior to sub-study registration
- •Patients must have received at least one line of anti-PD-1 or anti-PD-L1 therapy for stage III, IV or recurrent disease. Any number of additional, non-platinum-based chemotherapy or targeted therapy regimens for recurrent or metastatic disease are allowed
- •Patients may not have received more than one line of anti-PD-1 or anti-PD-L1 therapy in the Stage IV or recurrent setting. Anti-PD-1 or anti-PD-L1 therapy may have been given alone or in combination with platinum-based chemotherapy, an anti-CTLA4 therapy, or other immune-modulatory therapy. Patients must have experienced disease progression \> 42 days following initiation (cycle 1 day 1) of the anti-PD-1 or anti-PD-L1 containing regimen
- •Patients who did not receive anti-PD-1 or anti-PD-L1 therapy in combination with platinum-based chemotherapy, must have also received prior platinum-based chemotherapy and experienced disease progression \> 42 days following initiation (cycle 1 day 1) of platinum based chemotherapy
- •Patients who received anti-PD-1 or anti-PD-L1 therapy following concurrent chemoradiation for stage III disease as their only line of anti-PD-1 or anti-PD-L1 therapy, are eligible if they experienced disease progression less than (\<) 365 days from the date of initiation of anti-PD-1 or anti-PD-L1 therapy
- •Patients who received prior adjuvant platinum-based therapy post-surgical resection for stage I-III disease (i.e. the patient has not received platinum-based chemotherapy for Stage IV or recurrent disease) must have had disease progression during or after platinum-based chemotherapy that occurred less than (\<) 365 days from the last date that the patient received that therapy
Exclusion Criteria
- •Patients must not be pregnant or nursing. Women/men of reproductive potential must have agreed to use an effective contraceptive method. A woman is considered to be of "reproductive potential" if she has had menses at any time in the preceding 12 consecutive months. In addition to routine contraceptive methods, "effective contraception" also includes heterosexual celibacy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy, bilateral oophorectomy or bilateral tubal ligation. However, if at any point a previously celibate patient chooses to become heterosexually active during the time period for use of contraceptive measures outlined in the protocol, he/she is responsible for beginning contraceptive measures
- •Patients must not have a history of prior organ transplantation, including allogeneic stem-cell transplantation
- •Patients must not have received systemic treatment with corticosteroids (\> 10 mg daily prednisone or equivalent) or other immunosuppressive medications within 7 days prior to sub-study registration. Inhaled or topical steroids, and adrenal replacement doses =\< 10 mg daily prednisone or equivalent are permitted in the absence of active autoimmune disease
- •Patients must not have active autoimmune disease that requires systemic steroids (equivalent of \> 10 mg of prednisone) or immunosuppressive agents within 7 days prior to sub-study registration (for example disease-modifying anti-rheumatic drugs). Exceptions include: patients with controlled type 1 diabetes mellitus, controlled hypo- or hyperthyroidism, vitiligo, resolved childhood asthma/atopy, or psoriasis not requiring immunosuppressive therapy
- •Patients must not have any impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of talazoparib (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, small bowel resection, or active peptic ulcer disease). Patients must not have active small or large intestine inflammation such as Crohn's disease or ulcerative colitis within 12 months prior to sub-study registration
- •Patients must not have known prior or suspected hypersensitivity to monoclonal antibodies (grade \>= 3)
- •Patients must not have any history of anaphylaxis or uncontrolled asthma. Uncontrolled asthma is defined as a patient having any one of the following criteria:
- •Poor symptom control: Asthma Control Questionnaire (ACQ) consistently \> 1.5 or Asthma Control Test Questionnaire (ACT) \< 20 (or "not well controlled" by National Asthma Education and Prevention Program \[NAEPP\] or Global Initiative for Asthma \[GINA\] guidelines over the 3 months or evaluation)
- •Frequent severe exacerbations: 2 or more bursts of systemic corticosteroids (CSs) (\> 3 days each) in the previous year
- •Serious exacerbations: at least one hospitalization, intensive care unit stay or mechanical ventilation in the previous year
Arms & Interventions
Treatment (talazoparib, avelumab)
Patients 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.
Intervention: Talazoparib Tosylate
Treatment (talazoparib, avelumab)
Patients 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.
Intervention: Avelumab
Treatment (talazoparib, avelumab)
Patients 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.
Intervention: Talazoparib
Outcomes
Primary Outcomes
Disease Control Rate at 12 Weeks (DCR12)
Time Frame: 12 weeks after registration
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.
Objective Response Rate (ORR)
Time Frame: From date of registration to progression or treatment discontinuation, up to 1 year and 9 months
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.
Secondary Outcomes
- Overall Survival (OS)(From date of registration to a maximum of 3 years or death)
- Investigator-Assessed Progression-Free Survival (IA-PFS)(From date of registration to a maximum of 3 years or death)
- Duration of Response (DOR)(From date of registration to a maximum of 3 years or death)
- Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs(Duration of treatment and follow up until death or 3 years post registration)