This manuscript describes the experience from registration until randomisation for a cohort of 2260 patients with osteosarcoma who joined the EURAMOS-1 trial. This includes pre-operative chemotherapy and surgery. It sets out the practical issues in collaboration and in achieving randomisation.

Localised osteosarcoma will be cured in 50% of patients with cisplatin and doxorubicin. Large randomised trials can be conducted in this rare cancer. Failure to improve survival over 20 years argues for concerted collaborative international efforts to identify and rapidly test new treatments.

Background: The establishment of sublobar resection procedures for non-small cell lung cancer is expected. Many groups have suggested adenocarcinoma in situ (AIS) to be a potential indication for sublobar resection. Method: From 2012 to 2016, 80 patients (23 men and 57 women; median age, 70 years; range 40-86) diagnosed with adenocarcinoma in situ from intraoperative frozen sections, and underwent sublobar resection or lobectomy at our institution. Of these, 74 patients received sublobar resection and 6 patients underwent lobectomy. for adenocarcinoma in situ. We evaluate the predictive value of the intraoperative pathologic examination for AIS diagnosis, and overall survival, disease-free survival, and cancer-specific survival. Result: Permanent pathologic examination revealed 61patients had AIS, 17 patients had minimally invasive adnocarcinoma and 2 patients had invasive adnocarcinoma. The predictive value of intraoperative pathologic examination for AIS diagnosis was 79.3%. During a median 48-month follow-up, there were 1 cancer unrelated deaths. The 5-year overall survival rate was 98.8%. The disease-free survival rate and the 5-year cancerspecific survival rate were 100%. Conclusion: The results of our retrospective study indicate that an intraoperative pathologic diagnosis of AIS is strongly predictive and allows for an intraoperative decision to perform a sublobar resection in these patients.

9006 Background: Initial results with the amivantamab (ami) and lazertinib (laz) regimen showed encouraging efficacy in patients (pts) whose disease progressed after standard-of-care osimertinib (osi) and platinum-based chemotherapy (pt-chemo; Shu Ann Oncol 2021; 32:S949-1039; 1193MO). We present updated results of this population (Cohort A) from the CHRYSALIS-2 study (NCT04077463). Methods: Cohort A evaluated ami and laz in pts with EGFR exon 19 deletion or L858R NSCLC whose disease progressed on 1st/2nd-line osi followed by pt-chemo as last line of therapy (target population, n=106) and among a more heavily-pretreated population (n=56) whose disease progressed after osi and pt-chemo ± other therapies without regard to number and sequence of these therapies. Pts received 1050 mg IV ami (1400 mg, ≥80 kg) + 240 mg oral laz. Investigator (INV)- and blinded independent central review (BICR)-assessed response per RECIST v1.1 is reported for efficacy-evaluable pts, defined as pts who initiated study treatment on or before 17 Mar 2021, allowing for ≥6 mo of follow-up for response durability. Results: As of 6 Nov 2021, 162 pts were enrolled in Cohort A (median 62 y, 65% women, 61% Asian, median 3 [range, 2–14] prior lines). Median time between last osi treatment to first dose of ami + laz was 6.3 mo and 2.0 mo for the target and heavily-pretreated populations, respectively. Of 50 efficacy-evaluable pts in the target population, the overall response rate (ORR) by BICR was 36% (95% CI, 23–51), with 1 complete response (CR) and 17 partial responses (PRs), and the clinical benefit rate (CBR) was 58% (95% CI, 43–72); full results for all enrolled pts will be reported at the meeting. Median duration of response (mDOR) was not reached based on BICR. At a median follow-up of 8.3 mo, 7 responders (39%) have achieved a DOR lasting ≥6 mo by BICR. INV-assessed responses were consistent with BICR. Of 56 efficacy-evaluable pts in the heavily-pretreated population (8.7-mo median follow-up), ORR by INV was 29% (95% CI, 17–42), with 1 CR and 15 PRs. CBR was 55% (95% CI, 42–69) and mDOR was 8.6 mo (95% CI, 4.2–NR). BICR results are pending. Preliminary evidence of CNS antitumor activity was reported among 8 pts with baseline brain lesions (7 non-target, 1 target) who had not received radiation within 1 year prior to study enrollment. Most frequent adverse events (AE) were infusion-related reaction (65%), paronychia (49%), rash (41%), and stomatitis (39%). Most common grade ≥3 treatment-related AEs (TRAEs) were infusion-related reactions (7%), acneiform dermatitis (5%), and hypoalbuminemia (4%). TRAEs leading to discontinuation of either or both ami and laz occurred in 12% and 7%, respectively. Conclusions: Among an unselected population that has exhausted SOC osi and pt-chemo, ami and laz demonstrates encouraging antitumor activity with a manageable safety profile. Clinical trial information: NCT04077463.

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TPS8573 Background: Durvalumab, a selective, high-affinity, engineered human IgG1 mAb that blocks PD-L1 binding to PD-1 and CD80, is approved in the US, Japan and several other countries, for the treatment of patients (pts) with unresectable, stage III non-small cell lung cancer (NSCLC) whose disease has not progressed following concurrent chemoradiotherapy (cCRT). These approvals were based on results from the phase 3 PACIFIC study, in which durvalumab was given 1–42 days after completion of definitive cCRT and significantly improved progression-free survival (PFS) vs placebo (median 16.8 vs 5.6 months; HR 0.52, 95% CI 0.42– 0.65; p<0.001) and overall survival (OS) vs placebo (stratified HR 0.68; 99.73% CI 0.47–0.997; p=0.0025). Increasing evidence suggests additional benefit when anti-PD-1/PD-L1 therapies are administered alongside cCRT. The PACIFIC 2 study therefore aims to assess whether durvalumab plus cCRT provides additional benefit, in terms of PFS and objective response rate (ORR), compared with cCRT alone. Methods: PACIFIC 2 is a phase 3, randomized, double-blind, placebo-controlled, multicenter, international study. Approximately 300 pts with unresectable stage III NSCLC will be randomized (2:1) to receive either durvalumab (intravenous 1500 mg) every 4 weeks (q4w) + cCRT, or placebo q4w + cCRT. Eligible pts must have histologically or cytologically confirmed stage III disease; ECOG performance status 0 or 1; and life expectancy >12 weeks at randomization. Pts who discontinue treatment will be followed for safety and OS. Primary endpoints are PFS and ORR (RECIST v1.1) assessed via blinded independent central review. Secondary endpoints include OS; OS at month 24; complete response (CR) rate; duration of response; disease control rate; time to death/distant metastases; time from randomization to second progression; safety; and symptoms, functioning and global health status. Pts with a CR, partial response or stable disease will continue to receive durvalumab or placebo until clinical or RECIST v1.1-defined disease progression, or until another discontinuation criterion is met. Study enrollment began in March 2018 and recruitment is ongoing. Clinical trial information: NCT03519971.

TPS9132 Background: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have improved clinical outcomes for patients with EGFR mutant (EGFRm) non-small cell lung cancer (NSCLC); however, patients will inevitably progress due to acquired resistance mutations. Lazertinib is a potent, brain-penetrant, 3rd-generation EGFR TKI with efficacy against activating EGFR and resistance T790M mutations. Amivantamab is an EGFR-MET bispecific antibody with immune cell-directing activity that targets activating EGFR and MET mutations. Synergistic inhibition of the EGFR by targeting the receptor’s extracellular domain with amivantamab and the kinase domain with lazertinib, may lead to more potent inhibition of the EGFR pathway and potentially delay resistance. In the ongoing CHRYSALIS phase 1 study (NCT02609776), preliminary antitumor activity has been demonstrated with the combination of lazertinib and amivantamab in patients with treatment-naïve and osimertinib-relapsed EGFRm NSCLC (Cho Ann Oncol 2020;31:S813). Methods: CHRYSALIS-2 is an ongoing phase 1/1b open-label study of lazertinib as monotherapy and in combination with amivantamab in patients with advanced EGFRm NSCLC (NCT04077463; https://clinicaltrials.gov/ct2/show/NCT04077463 ). Phase 1 of the study has confirmed the safety and tolerability of lazertinib monotherapy in Japanese patients. The objective of phase 1b is to characterize the preliminary efficacy of lazertinib in combination with amivantamab in subpopulations of patients with EGFRm NSCLC (Phase 1b Expansion Cohorts) at the recommended combination dose of 1050 mg (1400 mg, ≥80 kg) IV amivantamab dosed weekly in cycle 1 (28-day cycle), every other week thereafter, and 240 mg oral lazertinib QD. Global enrollment in Phase 1b Expansion Cohorts is currently ongoing. Expansion Cohort A is enrolling patients who have progressed on 1st or 2nd-line osimertinib followed by platinum chemotherapy; Expansion Cohort B is enrolling patients with EGFR exon 20 insertion (Exon20ins) mutation who have progressed on prior therapy; and Expansion Cohort C is enrolling patients with uncommon non-Exon20ins EGFR mutations (i.e., S768I, L861Q, G719X) who are treatment-naïve or received 1st or 2nd-generation EGFR TKI as last therapy. The primary endpoints of the study are frequency of dose-limiting toxicity for phase 1 and 1b combination cohorts, and overall response rate for phase 1b expansion cohorts. Key secondary endpoints include safety (adverse events), pharmacokinetics, duration of response, clinical benefit rate, progression-free survival, and overall survival. Safety assessments will include monitoring AEs, clinical laboratory tests, ophthalmologic examination, ECG, and ECHO/MUGA. Blood samples will be collected to access PK. Tumor response will be assessed every 6 weeks by the investigator using RECIST, v1.1. Clinical trial information: NCT04077463.